Somerset, Wiltshire, Avon and Gloucestershire (SWAG) Cancer Services. Urology Cancer Network Site Specific Group. Clinical Guidelines.

Transcription

1 Somerset, Wiltshire, Avon and Gloucestershire (SWAG) Cancer Services Urology Cancer Network Site Specific Group June 2015 Revision due: April 2016 Page 1 of 55

2 VERSION CONTROL THIS IS A CONTROLLED DOCUMENT. PLEASE DESTROY ALL PREVIOUS VERSIONS ON RECEIPT OF A NEW VERSION. Please check the SWSCN website for the latest version available: VERSION DATE ISSUED SUMMARY OF CHANGE OWNER S NAME Draft th March 2015 Renal Cancer Update Multiple SSG members Draft th May 2015 Bladder Cancer Update Ed Rowe Draft th May 2015 Penile Cancer Update David Dickerson Draft th June 2015 Prostate Cancer Update Multiple SSG members th June 2015 Finalised SWAG Urology SSG Page 2 of 55

3 This document was edited by: Ed Rowe, Chair of the SWAG Urology SSG, Consultant Urologist, North Bristol Trust David Dickerson, Consultant Urologist, Weston Area Health NHS Trust Jonathan McFarlane, Consultant Urologist, Royal United Hospital Bath NHS Foundation Trust Francis Keely, Consultant Urologist, North Bristol NHS Trust Anthony Koupparis, Consultant Urologist, North Bristol NHS Trust Serena Hillman, Consultant Clinical Oncologist, Weston Area Health Trust Armarnath Challapalli, Consultant Clinical Oncologist, University Hospitals Bristol NHS Foundation Trust Emma Gray, Consultant Clinical Oncologist, Taunton and Somerset NHS Foundation Trust Helen Dunderdale, SWAG Cancer Network SSG Support Manager These clinical guidelines have been agreed by: Name Position Trust Date agreed Jonathan McFarlane Consultant Urologist Royal United Hospitals June 2015 Bath NHS Foundation Trust (RUH Nick Burns-Cox Consultant Urologist Taunton and Somerset June 2015 NHS Foundation Trust (TST) Chris Parker Consultant Clinical Yeovil NHS Foundation June 2015 Oncologist Trust (YDH) David Dickerson Consultant Urologist Weston Area Health June 2015 Trust (WAHT) Jeremy Braybrooke Consultant Medical University Hospitals June 2015 Oncologist Bristol NHS Foundation Trust Hugh Gilbert Consultant Urologist Gloucestershire Hospitals NHS Foundation Trust June 2015 Page 3 of 55

4 Urology NSSG Contents Contents Measures Page Section 1 Introduction 7 2 for Kidney Cancer 14-1C-105g Diagnosis Staging Investigations Specialist Nephrectomy Surgical Team Treatment Guidelines Pathology Reporting Follow-Up Rationale for follow up Principles Follow-up of renal tumour post nephrectomy Metastatic disease Surgical options Systemic therapy Radiotherapy 13 3 for Bladder Cancer 14-1C-106g Introduction Classification Patients to be Discussed at Regional MDT - Meeting Diagnosis Additional evaluations in muscle invasive and highrisk recurrent superficial bladder tumours 3.6 Treatment Treatment of high-risk superficial bladder tumours Treatment of high-risk superficial bladder tumours and muscle- invasive tumours Teams for Cystectomy Teams for Radiotherapy and Chemotherapy Radiotherapy Treatment of Metastatic Disease Follow Up Rationale for follow-up Principles Follow-up Procedures Page 4 of 55

5 4 for Prostate Cancer 14-1C-107g Introduction Referral Guidelines Protocol for GP referral to the Designated Prostate 14-2G-107 Assessment Clinic Diagnosis MDT Discussion Staging Investigations Radical Prostatectomy Team Treatment Guidelines Active Surveillance Follow-up after treatment with curative intent Definition of PSA progression PSA monitoring after radical prostatectomy PSA monitoring after radiation therapy Digital rectal examination (DRE) Bone scintigraphy Management of PSA Relapse after Radical Prostatectomy Management of PSA relapse after radiation therapy Hormonal Treatment Guidelines for follow-up after hormonal treatment Second Line Hormone Treatment Treatment of metastatic castration resistant prostate cancer (MRCP) Guidelines for Cytotoxic Therapy in MRCP Guidelines for Palliative Management of MRCP Facilities and Services of Host Trusts 29 5 for the management of Testicular 14-1C-108g Cancer 31 6 for Penile Cancer Including supranetwork information Introduction Named Supra network Team Referral criteria Multi-Disciplinary Team Meetings (MDT/MDM) Communication with local and diagnostic teams Local specialist teams for counselling and carrying out non-supra- network procedures/treatments Core team members to present options to 34 Page 5 of 55

6 patients 6.8 Facilities for patients Waiting times position Diagnosis and assessment Guidelines on Diagnosis of Penile Cancer Primary Lesion Regional Nodes Guidelines on the Treatment of Penile Cancer Treatment of the Primary Lesion Treatment of superficial non-invasive disease (Tis/CIS) Treatment of invasive disease confined to the glans (Ta/T1a) Treatment of invasive disease confined to the corpus spongiosum/glans (T2) Treatment of disease invading the corpora cavernosa and/or urethra (category T2/T3) Treatment of locally advanced disease invading adjacent structures (T3/T4) Local recurrence after organ-conserving surgery Management of the Regional Nodes Management of patients with clinically normal inguinal lymph nodes (cn0) Management of patients with palpable inguinal nodes (cn1/cn2) 42 Management of patients with fixed inguinal nodes (cn3) Management of lymph node recurrence Delayed Presentation of Positive Groin Nodes Metastatic Disease Clinical Trials Follow Up Operational policy for the Penile Cancer Supranetwork Multidisciplinary Team 7 Appendices Appendix 1. Radiotherapy and Chemotherapy Team Appendix 2. Imaging guidelines Appendix 3. Pathology Guidelines Appendix 4. Prostate Cancer Referral Proforma Page 6 of 55

7 1. Introduction The following guidelines pertain to the local management of urological malignancies for the Somerset, Wiltshire, Avon and Gloucestershire (SWAG) Network Urology Oncology Site Specific Group (NSSG). The NSSG refers to the National Institute for Health and Care Excellence (NICE) clinical guidelines: Primary care clinicians should refer to the NICE guidelines Suspected Cancer: recognition and management of suspected cancer in children, young people and adults (2015) for the signs and symptoms relevant when referring to urology oncology services. Further details on the two week wait referral process can be found in the NSSG constitution and within these clinical guidelines. The guidelines should be reviewed alongside three other key documents for the SSG: the Constitution, Annual Report and the Work Programme. The Urology SSG Constitution provides an overview of how the SSG operates, outlining its general working processes, the patient referral pathways and the guidelines to which the SSG adheres. The Annual Report reflects the period of activity for the SSG from the previous year. It contains a summary of the activity of the Urology SSG for this period, measured against several key performance indicators that have been outlined in the National Cancer Peer Review Programme. The Work Programme summarises the key areas for growth, development and improvement of the SSG over the next financial year (and beyond where appropriate). All four documents should be reviewed together to give a full overview of the SSG, its performance and future plans. The NSSG is committed to offering all eligible patients entry into clinical trials where available. Consent to provide tissue for research purposes will also be sought wherever appropriate. 2. for Kidney Cancer (measure 14-1C-105g) The following is based on the European Association of Urology guidelines (2007) and the NICE specific treatment guidelines. Renal Cell Carcinoma (RCC) is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There are no established risk factors and the current TNM system (UICC, 2012) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent; incidental discovery already constitutes a majority of cases. Page 7 of 55

8 Renal cell carcinoma (RCC) accounts for about 2-3% of all cancers, with a world-wide annual increase of %. The mean age at the time of diagnosis is about 70 years and there is a predominance of men over women in the range of 1.5:1. The mortality from RCC is increasing parallel to trends in incidence. In 2012, there were approximately 84,400 new cases of RCC and 34,700 kidney cancerrelated deaths in the European Union. The increased incidence of RCC is primarily due to enhanced detection of tumours by expanded use of imaging techniques, such as ultrasound and computed tomography (CT). At present, over 50% of clinically diagnosed RCC are found incidentally. A total of 25-30% of patients with RCC have overt metastases at initial presentation and, in addition, a substantial fraction of patients have subclinical metastases at that time explaining the hitherto unsatisfactory outcome of treatment. Survival is closely related to initial stage; 5-year survival is 50-90% for localised disease, decreasing to 0-13% for metastatic disease. There are no generally accepted risk factors for RCC. There is some epidemiologic data indicating that a smoking habit, obesity or hypertension, may favour the development of RCCs. 2.1 Diagnosis Clinical symptoms of RCC such as haematuria, palpable tumour and flank pain, are becoming less frequent. Asymptomatic tumours are more commonly diagnosed incidentally on investigation for other disease such as cholecystitis. Clinical examination has a limited role in diagnosing RCC, but it may be valuable in assessing co-morbidity. In cases of haematuria, additional tumours of the genitourinary tract should be excluded. The most commonly assessed laboratory parameters are: Haemoglobin: prognosis Creatinine: overall kidney function Alkaline phosphatase: liver metastasis, bone metastasis. Serum calcium is frequently included in the preoperative assessment because of its association with paraneoplastic manifestation, which may have clinical implications. Standard diagnostic procedure is an abdominal CT-scan with and without contrast medium (usually with chest and pelvis at the same time). It serves to document the diagnosis of RCC and provides information on the function and morphology of the contralateral kidney. Additional diagnostic procedures, such as magnetic resonance imaging, angiography or fine needle biopsy may be considered in selected cases. 2.2 Staging Investigations CT scan chest/abdo/pelvis (or MRI) should be used to assess primary tumour extension and provide information on venous involvement, to loco-regional lymph nodes and metastatic spread. Specific angiographic modalities should be used to assess vena caval involvement if suspected, and Page 8 of 55

9 to provide a road map in patients for nephron sparing surgery. If indicated by signs and symptoms, other diagnostic procedures may be appropriate, such as bone scan or CT head. All new cases of renal cancer will be reviewed at the local MDT meeting. Any case of incidental RCC may be referred to the Specialist MDT for review. This may include patients with significant comorbidity on whom active monitoring may be justified. Patients that must be referred to the specialist MDT for discussion include: 1. All patients considered for nephron sparing surgery (defined below) 2. Patients with metastatic disease considered for debulking nephrectomy 3. Resection of tumours in patients with hereditary RCC 4. Patients with bilateral disease 5. Patients to be considered for novel therapies (Cryotherapy) 6. Patients likely to require post-operative renal dialysis 7. Patients with organ confined disease not fit for nephrectomy but requiring palliative local treatment 8. Patients with urothelial and, if known, pre op non renal cell kidney cancer 9. Patients for adjuvant therapy and/or trial inclusion 10. Patients with IVC involvement. 2.3 Specialist Nephrectomy Team: Surgical Joe Philip, Consultant Urologist NBT Salah Al-Buheissi, Consultant Urologist, NBT Frank Keeley, Consultant Urologist, NBT Mark Wright, Consultant Urologist, NBT Tim Whittlestone, Consultant Urologist, NBT. 2.4 Treatment Guidelines Only radical surgery offers a reasonable chance of curing the disease. The chances of cure by surgery most strongly depend on stage (primarily) and grade (secondarily) of the disease. Standard operative procedure is a radical nephrectomy including Gerota s fascia. There is no evidence to favour a specific surgical approach. In cases of T1a or T1b lesions, the preferred option is for nephron-sparing surgery whenever practically possible. All T1 cases should therefore be considered for discussion at the specialist MDT. Page 9 of 55

10 If surgery cannot eradicate all tumour deposits, palliative nephrectomy should be considered in the context of multimodality treatment (e.g. in conjunction with Tyrosine Kinase Inhibitors or experimental therapies). These cases should be identified at the local MDT and referred for discussion at the specialist meeting. Certain cases, such as bilateral tumours, a solitary tumour-bearing kidney, multifocal lesions, renal insufficiency, or an occasional palliative situation, will require individual decisions not amenable to general guidelines and will require discussion at the specialist MDT. 2.5 Pathology Reporting The reporting of specimens should follow the RC Path minimum dataset, preferably also noting the presence of microvascular invasion. This will incorporate TNM staging (2012). Traditionally RCC have been classified according to the nuclear or cellular morphology. New morphologic, cytogenetic and molecular studies make it possible to distinguish three main types of carcinomas: Clear cell: 80-90% Papillary: 6-15% Chromophobic: 2-5%. Recent attempts have been made to generate a molecular classification. 2.6 Follow-Up Rationale for follow up Follow up of patients with RCC after surgical treatment is recommended to detect local recurrence, and distant metastases, as early as possible to permit additional treatment when indicated and if possible. Such therapy may include resection of pulmonary metastasis or local recurrences and certain cases may also be candidates for Tyrosine Kinase Inhibitors. With this background in mind, a regular postoperative follow up of patients with RCC is proposed Principles Prognostic factors and the type of surgical intervention (radical vs. partial or nephron sparing surgery) are relevant in determining the most efficient follow up regimen. The most established prognostic factors are tumour stage according to the TNM system and presence of microvascular invasion. The Leibovich score gives an indication of prognosis and is determined by tumour size, stage, grade, nodal involvement and the presence or absence of necrosis. Results of recent trials (including the SORCE trial) exploring the role of adjuvant Tyrosine Kinase Inhibitors are awaited at time of print (April 2015). After nephron-sparing tumour resection (elective or mandatory indication), the local recurrence rate may vary between 0 and 10%. In a small proportion of patients with a genetic predisposition, a different follow-up procedure may be required Follow-up of renal tumour post nephrectomy Page 10 of 55

11 Table 1. Tables for suggested follow-up protocols of low to high risk renal cell carcinoma. MRI is equivalent to CT for follow-up, and either can be used. Low risk (Radical nephrectomy or partial nephrectomy only) Year 6 months Discharge after 5 years follow-up. Hx/PE X X X X X X EGFR X X X X X X Uss X X X CT chest/abdo X X X Intermediate risk (Radical nephrectomy/partial nephrectomy/cryotherapy/radiofrequency ablation) Year 6 months Then 2 yearly CT chest/abdo Hx/PE X X X X X X EGFR X X X X X X Uss CT chest/abdo X X X X X X Page 11 of 55

12 High risk (Radical nephrectomy/partial nephrectomy/cryotherapy/radiofrequency ablation) Year 6 months Then 2 yearly CT chest/abdo Hx/PE X X X X X X EGFR X X X X X X CT chest/abdo X X X X X X 2.7 Metastatic disease Surgical options Cytoreductive nephrectomy should be considered in patients with relatively low volume metastases prior to systemic treatment, with the aim of debulking the disease burden and potentially improving outcomes following drug therapy. Palliative nephrectomy should be considered in specific cases for patients with more advanced metastatic disease with the aim of controlling local symptoms such as bleeding or pain. Metastatectomy should be considered in the case of solitary (or few) metastases when the disease is slowly progressive and otherwise well-controlled, particularly, for example, if confined to one lobe of the lung. For patients with solitary brain metastases, neurosurgical intervention or stereotactic radiotherapy should be considered Systemic therapy Sunitinib or pazopanib are approved for use as first line therapy in metastatic disease in patients with a good performance status (WHO 0 or 1). The standard schedule of sunitinib is 50 mg po daily for 4 weeks followed by 2 weeks rest. The 6- weekly cycles are continued to progression or intolerance (unless part of a clinical trial eg STAR). Doses can be reduced in increments of 12.5mg if poorly tolerated. Common side effects include sore mouth, diarrhoea, fatigue, sore hands/feet, hypertension and thrombocytopaenia. Axitinib may be considered in some situations as second line therapy. Interferon alpha is an option if patients are unsuitable or fail to tolerate TKIs. Response rates are unimpressive and side effects are common (particularly fatigue, arthralgia and headaches). Page 12 of 55

13 2.7.3 Radiotherapy Palliative radiotherapy should be considered for painful bone metastases or to control local symptoms such as bleeding. Table 2. Mayo risk assessment. Risk categories following a radical nephrectomy to prognosticate low to high risk of future metastasis development. Mayo risk assessment Tumour staging 1a 0 1b Apr 4 LN status Nx 0 N0 0 N1 2 N2 2 Tumour Size <10 0 >10 1 Nu clear grade Tumour Necrosis No 0 Yes 1 Total Please 0-2 Low circle 03- Intermediate May >6 High ECOG/ WHO performance status (0-4) _ Is the patient fit, able and willing to undergo recommended follow-up? Y/N Page 13 of 55

14 3. for Bladder Cancer (measure 14-1C-106g) 3.1 Introduction The incidence of bladder carcinoma is rising in Western countries. Approximately 75-85% of patients present with disease confined to the mucosa (stage Ta-Tis) or submucosa (stage T1). The other 15-25% have muscle invasion or nodal disease (stages T2-T4, N+) at presentation. The management of superficial bladder cancer has become more complex, with urological opinion differing with regard to initial investigation, treatment and follow-up. The following guidelines entail our policy for all bladder tumour patients who are discussed at the regional MDT meeting. 3.2 Classification The following TNM staging is sourced from the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer-Verlag New York, TX: The primary tumour cannot be evaluated. T0: There is no evidence of a primary tumour in the bladder. Ta: This refers to non-invasive papillary carcinoma. This kind of growth is often found on a small section of tissue that can easily be removed with TURBT and tends to be recurrent (comes back after treatment). Tis: This stage is carcinoma (cancer) in situ, or "flat tumour." This means that the cancer is only found in cells within the lining of the bladder. The doctor may also call it non-muscleinvasive/superficial bladder cancer or non-invasive flat carcinoma (the cancer is on or near the surface of the bladder). This type of bladder cancer often comes back after treatment, usually as another non-invasive cancer in the bladder. T1: The tumour has spread to the sub-epithelial connective tissue but does not involve the bladder wall muscle (lamina propria, the tissue below the inside lining of the bladder). T2: The tumour has spread to the muscle of the bladder wall. T2a: The tumour has spread to the inner half of the muscle of the bladder wall, which may be called the superficial muscle. T2b: The tumour has spread to the deep muscle of the bladder (the outer half of the muscle). T3: The tumour has grown into the perivesical tissue (the fatty tissue that surrounds the bladder). T3a: The tumour has grown into the perivesical tissue, as seen through a microscope. Page 14 of 55

15 T3b: The tumour has grown into the perivesical tissue macroscopically, meaning that the tumour(s) is large enough to be seen during imaging tests or to be seen or felt by the doctor. T4: The tumour has spread to any of the following: the abdominal wall, the pelvic wall, a man s prostate or seminal vesicle (the tube(s) that carry semen), or a woman s uterus or vagina. T4a: The tumour has spread to the prostate, uterus, or vagina. T4b: The tumour has spread to the pelvic wall or the abdominal wall. Node. The N in the TNM staging system stands for lymph nodes, the tiny, bean-shaped organs that help fight infection. Lymph nodes near where the cancer started, within the true pelvis (called hypogastric, obturator, iliac, perivesical, pelvic, sacral, and presacral lymph nodes), are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes. NX: The regional lymph nodes cannot be evaluated. N0: The cancer has not spread to the regional lymph nodes. N1: The cancer has spread to a single regional lymph node in the pelvis. N2: The cancer has spread to more than one regional lymph node in the pelvis. N3: The cancer has spread to the common iliac lymph nodes, which are located behind the major arteries in the pelvis, above the bladder. Distant metastasis. The "M" in the TNM system indicates whether the cancer has spread to other parts of the body. M0: The disease has not metastasized. M1: There is distant metastasis. All bladder cancers are graded into the low, intermediate and high risk categories as per the NICE guidance (2015), page Treatment options for each category including follow up protocols are in line with NICE guidance (2015), page 15 onwards. 3.3 Patients to be Discussed at Regional MDT - Meeting The following patients will be discussed at the regional MDT meeting: Muscle invasive or high-risk recurrent superficial bladder tumours (M0) T1, any G3 and any Cis associated tumours Any > T2 tumours Page 15 of 55

16 Non-responders to conservative treatment (M0) Relapse after bladder-sparing treatments (M0) Non-transitional cell carcinomas (M0). 3.4 Diagnosis Mandatory evaluation Physical Examination Renal and bladder ultrasonography and/ or IVP Cystoscopy with description of the tumour Urinary cytology Trans urethral resection with: Biopsy of the underlying tissue Random biopsies in the presence of positive cytology, large or non-papillary tumour Biopsy of the prostatic urethra in cases of Tis or suspicion of it. 3.5 Additional evaluations in muscle invasive and high-risk recurrent superficial bladder tumours CT scan of chest, abdomen and pelvis Bone scan if symptoms are present or alkaline phosphatase level is elevated MRI pelvis if there is discrepancy between CT staging and Trans Urethral Resection of Bladder Tumour (TURBT). 3.6 Treatment Treatment of high-risk superficial bladder tumours Re-resection 4-6 weeks after the initial TUR. If re-resection confirms the initial stage and grade, it will not be upstaged to T2 6 week course of chemotherapy (40 MMC) followed by monthly instillations up to 6 months As an alternative, a 6 week course of BCG, followed by a 3 week cycle at 3 months Maintenance BCG schedule according to Lamm with 3 instillations at 3, 6, 12, 18, 24, 30 and 36 months Maintenance BCG schedule for intermediate risk NMIBC if the patient is able to tolerate side effects Close endoscopic surveillance. In the event of a shortage of BCG, further treatment options that might be used as an alternative are being explored. Page 16 of 55

17 3.6.2 Treatment of high-risk superficial bladder tumours and muscle- invasive tumours Cystectomy If patients are considered fit for major surgery. All cases of muscle invasive grade three TCC bladder should be considered for neo-adjuvant chemotherapy. Limited lymph node dissection Preservation of the urethra if the margins are negative (intraoperative frozen section) All types of urinary diversion are offered to the patient, depending on their fitness, age, general status and tumour location (not for neo-bladder if the intraoperative frozen section of the urethral margin is positive) Patients will be seen in the joint uro-oncology clinic and possible alternatives, including radiotherapy, will be offered Patients will be counselled by a surgeon, an oncologist and a clinical nurse specialist from the core team. They will be offered the opportunity to meet other patients who have already undergone a cystectomy, other types of diversion or radiotherapy High risk cases post cystectomy should be discussed at the regional MDT, and particularly those with node positive disease should be considered for adjuvant chemotherapy. 3.7 Teams for Cystectomy Core Team Mr David Gillatt, Consultant Urologist, NBT Mr Ed Rowe, Consultant Urologist, NBT Mr Raj Persad, Consultant Urologist, NBT Mr Anthony Koupparis, Consultant Urologist, NBT Extended Team Mr John Mc Farlane, Consultant Urologist, RUH Mr David Dickerson, Consultant Urologist WHAT Mr Rupert Beck, Consultant Urologist Swindon and Marlborough NHS Trust. 3.8 Teams for Radiotherapy and Chemotherapy please see Appendix Radiotherapy Patients with adequate bladder capacity Normal bladder function No recurrent urinary tract infections Page 17 of 55

18 No previous inflammation or surgery of the true pelvis with consecutive adhesions. Radiotherapy after neo-adjuvant chemotherapy (NACT) is an option for patients considering bladder preservation if the cystoscopy post NACT is shown to be clear. Chemo-radiotherapy should be considered if a patient is deemed fit and can be recruited to the BC2001 clinical trial. Contraindication for radiotherapy Severe bladder symptoms (diversion) Inflammatory bowel disease Extensive pelvic surgery (adhesions) Extensive CIS Bilateral hydronephrosis Previous pelvic radiotherapy. Treatment Non responders to conservative treatment Relapse after bladder-sparing treatments Non-transitional cell carcinomas. Salvage Cystectomy will be considered if patients are deemed fit for major surgery Treatment of Metastatic Disease Chemotherapy Gemcitabine / cisplatin and gemcitabine / carboplatin are both used as up-front chemotherapy for metastatic disease depending on the patient s renal function and performance status. Median survival is months Taxane based chemotherapy for second line chemotherapy The palliative care team should be involved from an early stage Follow Up Rationale for follow-up Follow-up of patients with invasive bladder cancer after cystectomy and radiotherapy is recommended to detect local recurrence, and distant metastases, as early as possible to permit Page 18 of 55

19 additional treatment when indicated and if possible. Such therapy may include salvage cystectomy, urethrectomy, nephro-ureterectomy and or systemic chemotherapy, with and without secondary surgery, for residual tumour. Moreover, side effects of urinary diversion should be recognized early on and corrected if possible Principles Prognostic factors and type of intervention (cystectomy, radiotherapy) are relevant in determining the most efficient follow-up regimen. The pt and pn- stage are the most important prognostic factors and, in addition, risk factors such as ptis will guide the follow-up procedures Follow-up Procedures Cystectomy The first assessment is at three months postoperatively and includes: Physical examination Serum creatinine Urine analysis CT Urogram or IVU Chest-X-ray or CT. In case of unremarkable findings regular follow-up at intervals of 4 months are indicated. In cases of pn+ additional regular CT scans and bone scintigraphy are necessary. PTis patients need regular assessment of the upper urinary tract. Barbotage cytology is recommended for the remaining urethra. Radiotherapy The first assessment is at three months post-radiotherapy and includes: Physical examination CT scan of abdomen and pelvis Cystoscopy. The main interest during follow-up remains the bladder, because of the high local failure rate. Page 19 of 55

20 4. Clinical guidelines for Prostate Cancer (measure 14-1C-107g) 4.1 Introduction These guidelines are based on those produced by the European Association of Urology (2014) and NICE clinical guideline, CG175, Prostate Cancer: diagnosis and treatment, (January 2014). 4.2 Referral Guidelines Patients presenting with symptoms suggesting prostate cancer should have a digital rectal examination (DRE) and prostate-specific antigen (PSA) test after counselling. Symptoms will be related to the lower urinary tract and may be inflammatory or obstructive. Prostate cancer is also a possibility in male patients with any of the following unexplained symptoms: Erectile dysfunction Haematuria Lower back pain Bone pain Weight loss, especially in the elderly. These patients should also be offered a DRE and a PSA test. Urinary infection should be excluded before PSA testing, especially in men presenting with lower tract symptoms. The PSA test should be postponed for at least 1 month after treatment of a proven urinary infection. If a hard, irregular prostate typical of a prostate carcinoma is felt on rectal examination, then the patient should be referred urgently. The PSA should be measured and the result should accompany the referral. Patients do not need urgent referral if the prostate is simply enlarged and the PSA is in the age-specific reference range. 1 In a male patient with or without lower urinary tract symptoms and in whom the prostate is normal on DRE but the age-specific PSA is raised or rising, an urgent referral should be made. In those patients whose clinical state is compromised by other comorbidities, a discussion with the patient or carers and/or a specialist in urological cancer may be more appropriate. Symptomatic patients with high PSA levels should be referred urgently. 1 The age-specific cut-off PSA measurements recommended by the Prostate Cancer Risk Management Programme are as follows: aged years > 3.0 ng/ml; aged years > 4.0 ng/ml; aged 70 years and older > 5.0 ng/ml. (Note that there are no age-specific reference ranges for men aged over 80 years. Nearly all men of this age have at least a focus of cancer in the prostate. Prostate cancer only needs to be diagnosed in this age group if it is likely to need palliative treatment.) Page 20 of 55

21 If there is doubt about whether to refer an asymptomatic male with a borderline level of PSA, the PSA test should be repeated after an interval of one to three months. If the second test indicates that the PSA level is rising, the patient should be referred urgently. 4.3 Protocol for GP referral to the Designated Prostate Assessment Clinic (measure 14-2G-107) Details on referral can be found in the Trusts Operational Policies. See appendix 4 for the Prostate Cancer referral proforma. 4.4 Diagnosis Patients usually present with raised PSA or suspicious findings on rectal examination. Each urology department should provide rapid access prostate assessment clinics. The role of the multiparametric MRI prior to biopsy remains unclear, awaiting the results of the PROMIS study. The technique can be used to facilitate targeting of biopsies, or as a way of avoiding biopsy altogether. Studies have shown a normal scan gives a low risk of significant prostate cancer (Gleason pattern 4 or 5 disease). MRI should only be used prior to biopsy if an expert in performing and interpreting the test is available; patients should be counselled about the uncertainties of diagnosis by imaging alone. If a biopsy is not performed, the patient should be put on close PSA surveillance. Ultrasound-guided transrectal prostate biopsies should be obtained using an 18G core biopsy under local anaesthesia with antibiotic prophylaxis. A minimum of 10 cores should be taken unless the biopsies are being performed for confirmation in clinical T3-T4 disease. Treatment may occasionally be initiated without histological diagnosis in elderly patients with a high PSA and a clinically malignant prostate. Transperineal TRUS-guided template or targeted biopsies under general anaesthetic are appropriate alternatives to transrectal TRUS biopsy in selected patients. All tumour specimens will be handled and recorded in accordance with the Royal College of Pathologists minimum dataset for prostate Cancer histopathology reports, incorporating the TNM staging 7 edition (2009). 4.5 MDT Discussion All diagnoses of prostate cancer should be reviewed at the local MDT meeting. Urological cancer MDTs should assign a risk category to all newly diagnosed men with localised prostate cancer. Table 4. PSA Gleason Score Clinical Stage Low Risk <10 6 T1-T2a Intermediate risk T2b High risk > >T2c The following cases should be referred to the Network MDT: Page 21 of 55

22 All complex cases of patients being considered for radical treatment Local MDT recommendation. Patients with negative biopsies should have their risk factors reviewed by a member of the MDT and be offered follow-up with PSA or a repeat biopsy. The presence of a high grade prostatic intraepithelial neoplasm (PIN), atypical small acinar proliferation (ASAP) or abnormal digital rectal exam (DRE) all slightly increase the risk of cancer. Multiparametric MRI may be used instead of, or prior to, repeat biopsy if an expert in performing and interpreting the scans is available. Re-biopsy should be avoided if the scan is negative. 4.6 Staging Investigations Imaging should not be used routinely in men who are not candidates for radical therapy. Prior to radical therapy full staging investigations should be used for high risk tumours. Pelvic imaging should be considered for intermediate risk tumour if knowledge of the T or N stage would influence clinical management. Pelvic imaging should be performed with MRI (or CT if MRI is contraindicated). Bony imaging is usually obtained with bone scanning, but MRI with complete vertebral strip is an alternative. Bony imaging should also be requested in patients with bone pain. 4.7 Radical Prostatectomy Team David Gillatt, Consultant Urologist NBT Ed Rowe, Consultant Urologist NBT Anthony Koupparis, Consultant Urologist, NBT Mark Wright, Consultant Urologist, NBT Raj Persad, Consultant Urologist, NBT Jon McFarlane, Consultant Urologist RUH Jaspal Phull, Consultant Urologist, NBT Tim Porter, Consultant Urologist YDH. Ru McDonagh, Consultant Urologist TST. Teams for Chemotherapy and Radiotherapy- please see Appendix Treatment Guidelines Watchful waiting should generally be used for men with a life expectancy of less than 10 years. For men with a life expectancy greater than 10 years, treatment will be guided according to clinical risk: Low risk disease Active surveillance is the preferred option Page 22 of 55

23 Radical prostatectomy, LDR brachytherapy or HDR brachytherapy monotherapy, and radical radiotherapy are appropriate Intermediate risk disease Offer radical treatment options (surgery, external beam radiotherapy, HDR brachytherapy) Active surveillance not appropriate LDR brachytherapy not appropriate High risk disease Offer radical treatment options (surgery, external beam radiotherapy, HDR brachytherapy) Active surveillance not appropriate LDR brachytherapy not appropriate N+ disease Hormone therapy is the standard treatment Radical radiotherapy to prostate and pelvis should be considered Surgery (only after Network MDT approval) Offer watchful waiting to men who decline hormone therapy M+ disease Hormone therapy is the standard treatment Men with intermediate and high risk prostate cancer offered radical radiotherapy should have a minimum of 6 months of androgen deprivation therapy, and consider extending this for up to three years. Offer intermittent hormone therapy for men on long-term androgen deprivation therapy after discussion of the rationale, risks and benefits. Treatment options and counselling patients: For discussion of radical options, patients will have the opportunity of seeing a surgeon, oncologist and a clinical nurse specialist from the designated specialist teams in NBT, RUH, TST, WAHT and UH Bristol. 4.9 Active Surveillance Active surveillance is suitable for any patient with localized prostate cancer who is to be considered for radical treatment by the Network MDT. The most appropriate cases would be those with Gleason 6 disease, small volume disease, up to T2a, PSA <10. Protocol Repeat PSA at least every 3 months during the first 2 years, thereafter every 6 months Consider performing baseline multiparametric MRI after 3-6 months Repeat prostate biopsies within the first 6-12 months to look for undergrading Repeat prostate biopsies at 5 years Digital rectal examination with clinical review every months. Page 23 of 55

24 Re-biopsy will be considered if: Sharp rise in PSA or change in PSA kinetics Change in clinical stage Patient develops symptoms suggestive of local or distant progression. Refer back to local MDT for consideration of radical treatment if: PSA doubling time is less than 2 years Increase in Gleason score or number of cores on re-biopsy Patient request for radical treatment. The role of multiparametric MRI in active surveillance protocols remains uncertain. If an index lesion has been identified on scanning, consider repeat scans every 2-3 years Follow-up after treatment with curative intent The measurement of PSA levels is a cornerstone of follow-up after curative treatment. PSA recurrence nearly always precedes clinical recurrence, in some cases by many years Definition of PSA progression Following Radical Prostatectomy, two consecutive values of 0.2 ng/ml or greater appear to represent an international consensus defining recurrent cancer. Radiotherapy biochemical relapse is defined according to international guidelines (ASTRO guidance defines PSA >nadir +2.0 ng/ml as relapse post radiotherapy), It is essential to define PSA parameters for relapse for GPs when discharging the patient to their care PSA monitoring after radical prostatectomy PSA at 6 weeks post-op, thereafter: PSA every 3-6 months for 2 years PSA every 6-12 months beyond 2 years Outpatient follow-up until continence and potency satisfactory. Once the patient is physically well and psychologically adapted to their cancer treatment, remote follow-up with PSA is acceptable. Regular outpatient review for Gleason grade 8-10 tumours where PSA might not be as reliable should be considered PSA monitoring after radiation therapy PSA levels should be checked 6-8 weeks after radiotherapy, thereafter: Page 24 of 55

25 PSA every 3-6 months for 2 years PSA 6-12 monthly beyond 2 years Consider GP PSA follow up after 5 years. Once the patient is physically well and psychologically adapted to their cancer treatment, remote follow-up with PSA is acceptable Digital rectal examination (DRE) There is no evidence DRE improves detection of cancer recurrence following radical therapy; it should not be used routinely Bone scintigraphy Bone scintigraphy is not recommended for the routine follow-up of asymptomatic patients Management of PSA Relapse after Radical Prostatectomy The first option is to consider the RADICALS trial for suitable patients. The patient should be referred to the local Network MDT to consider salvage radiotherapy if: Definitive histology shows T3 tumour with positive surgical margins Detectable PSA immediately following surgery PSA >0.1 and 2 consecutive PSA rises Repeat staging prior to salvage radiotherapy is not useful in most cases Biopsy of the anastamosis is not recommended Expectant management is an option for patients with presumed local recurrence unfit for, or unwilling to undergo, radiation therapy PSA recurrence indicative of systemic relapse is best treated by early ADT resulting in decreased frequency of clinical metastases LHRH analogues/orchiectomy or bicalutamide at 150 mg/day can both be used when there is indication for hormonal therapy Management of PSA relapse after radiation therapy Local recurrences may be treated by salvage radical prostatectomy in carefully selected patients. Hormonal therapy is an alternative to be considered, depending on the original disease features. Androgen Deprivation Therapy (ADT) is preferred in patients with presumed systemic relapse Hormonal Treatment Patients suitable for hormonal treatment (as per EAU guidelines): Table 5: Page 25 of 55

26 Antiandrogens Short-term therapy To reduce flare except in cases of LH/RH antagonists Non-steroidal Monotherapy as an alternative to castration in locally advanced disease anti-androgens Castration M1 symptomatic M1 asymptomatic To palliate symptoms and to reduce the risk of complications (spinal cord compression, pathological fractures, urethral obstruction, extra-skeletal metastasis) Immediate castration to defer progression to a symptomatic stage and prevent serious progressionrelated complications N+ Immediate castration to prolong progression- free and even overall survival Locally advanced M0 Immediate castration to improve cancer-free survival Page 26 of 55

27 Locally advanced asymptomatic If unfit for local definitive treatment Guidelines for follow-up after hormonal treatment Follow-up should be tailored for the individual patient, according to disease stage, symptoms, prognostic factors and the treatment given. In general, patients should be evaluated at two to three months after initiating treatment. Tests should include serum PSA measurement, testosterone levels, and evaluation of symptoms in order to assess treatment response and side-effects. In patients with stage M0 disease with a good treatment response, follow-up is scheduled every 6-12 months. In patients with stage M1 disease with a good treatment response, follow-up is scheduled every 3-6 months. Routine imaging in stable patients is not recommended. Remote follow-up is appropriate for stable patients as long as there is a mechanism in place for identification and re-referral of patients. Docetaxel chemotherapy should be offered to fit, newly diagnosed patients with metastatic disease when starting androgen deprivation therapy, in view of recent trial results indicating a significant survival benefit for early chemotherapy in this group Second Line Hormone Treatment Castration resistant prostate cancer (CRPC) implies that disease progression occurs despite castration. Castration levels of testosterone should be documented to confirm adequate antiandrogen therapy and compliance. Luteinizing Hormone-releasing hormone (LH- RH) analogues should be continued indefinitely. Anti-androgens Except in patients with non-castration testosterone levels, it remains difficult to predict which subset of individuals is most likely to respond to secondary hormonal strategies. Anti-androgens may produce a biochemical response in these patients. Anti-androgen withdrawal syndrome Approximately one-third of patients on combined androgen blockade (CAB) will show a biochemical response to oral antiandrogen withdrawal as indicated by a 50% PSA decrease Treatment of metastatic castration resistant prostate cancer (MRCP) Abiraterone or enzalutamide can be used in the pre-chemotherapy setting for patients with Page 27 of 55

28 metastatic disease who are asymptomatic or minimally symptomatic with a WHO performance status of 0 or 1. Dexamethasone 0.5mg daily or stilboestrol with aspirin may be used after MAB and anti-androgen withdrawal Guidelines for Cytotoxic Therapy in MRCP As per NICE guidance: Potential benefits of cytotoxic therapy and expected side effects should be discussed with each individual patient In patients with metastatic CRPC, and who are candidates for cytotoxic therapy, docetaxel at 75 mg/m2 every 3 weeks, with prednisolone 5mg bd, for 6-10 cycles has shown a significant survival benefit, and should be considered in good performance status (PS) patients. Abiraterone or enzalutamide can be offered to patients in the post-chemotherapy setting, upon progression, in patients who have not already received these drugs Guidelines for Palliative Management of MRCP Management of these patients has to be directed at improvement of QoL and mainly pain reduction Effective medical management with the highest efficacy and low frequency side effects represents the major goal Zoledronic acid should be considered for pain relief when analgesics and palliative radiotherapy have not been successful, depending on the patient s renal function Palliative treatments such as radionuclides, external beam radiotherapy, and adequate use of analgesics should be considered early on in the management of painful osseous metastases Radium 223 should be considered in symptomatic patients with skeletal metastases, but no evidence of visceral metastases or lymph node metastases over 3cm in size. This can be used in the pre (through CDF funding) or post chemotherapy setting (NICE approved). Patients being offered this should have adequate bone marrow reserve according to local protocols Men with extensive spinal bony metastases should have an MRI if they develop new spinal symptoms. Protocols for the management of malignant spinal cord compression should be followed Facilities and Services of Host Trusts Radical prostatectomies are carried out in the Urology cancer centre in North Bristol Trust, the Taunton and Somerset NHS Trust, and the Royal United Hospital Bath NHS Trust. Radical radiotherapy is performed at UH Bristol, including HDR brachytherapy, and LDR brachytherapy is performed at TST and RUH. Services and facilities in North Bristol Trust: Dedicated Urology outpatients department with access to specialist and core team members Dedicated Urology wards Dedicated Urology theatres Page 28 of 55

29 Urology oncology clinical nurse specialists Lymphoedema service Psychosexual counselling network. The services and facilities in Taunton and Somerset NHS Trust are: All cases discussed at central specialist MDT Dedicated Urology outpatients department Dedicated Urology ward Urology clinical nurse specialists Dedicated Prostate Cancer Clinic Post operative unit and ICE clinic. Services and facilities available in RUH Bath: Dedicated Urology outpatients department Dedicated Urology theatres Urology clinical nurse specialists (x2) Dedicated joint Uro-oncology clinics (3 per week) Survivorship programme Weekly andrology service Psychological support service. Services available in WAHT: Dedicated Urology outpatients department Dedicated Urology theatres Urology clinical nurse specialists (x2) Dedicated joint uro-oncology clinics (1 per week) Access to a patient counselling service Andrology service Dedicated continence / urodynamic monthly clinic Macmillan information and CAB advisor. Services available in UH Bristol: Dedicated Uro-oncology outpatients clinic led by 4 Uro-oncologists Urology clinical nurse specialist Radiotherapy including image guided radiotherapy and HDR brachytherapy Page 29 of 55

30 Radium 233 service Complex case meeting weekly, supported by palliative care Cancer information and support centre. 5. for the management of Testicular Cancer (measure 14-1C-108g) The NSSG agreed clinical guidelines for testicular cancer is recorded in a separate document uploaded on the SWSCN website here. Page 30 of 55

31 6. for Penile Cancer Including supra-network information (measure 14-1C-109g) 6.1 Introduction The NICE Improving Outcomes Guidance on Urological Cancers recommend that all new cases of carcinoma of the penis should be reviewed by a specialist penile cancer team and that men who are likely to require organ conserving treatment, reconstruction or node clearance surgery are managed by a supra-network team each providing care for a population of 4 million or more. In ASWCS this team is established in North Bristol Trust Southmead site and currently receives referrals from the following Networks; SWAG Three Counties Network Peninsula Network 2.1 million population 1.3 million population 1.7 million population Local teams around the Network carry out diagnostic procedures including biopsy or circumcision and may treat penile cancer with surgery without penile reconstruction or lymph node resection. 6.2 Named Supra network Team Table 6: Name Title Trust Core Team Mr David Dickerson Consultant Urologist Weston Area Health NHS Trust Mr Ed Rowe Consultant Urologist North Bristol Trust Mr Tim Porter Consultant Urologist Taunton & Somerset Trust Clare Wyatt MDT Co-ordinator North Bristol Trust Dr Jon Oxley Histopathologist North Bristol Trust Dr Mark Thornton Radiologist North Bristol Trust Page 31 of 55

32 Dr Amit Bahl Dr Mark Beresford Dr Serena Hilman Dr Andrew Mitchelmore Sr Catherine Hurd, Mr Peter Gill, Sr Sharon Tonkin Oncologist Oncologist Oncologist Radiologist Uro-oncology nurse specialists University Hospitals Bristol NHS Foundation Trust University Hospitals Bristol NHS Foundation Trust Weston Area Health NHS Trust North Bristol Trust North Bristol Trust, Weston Area Health NHS Trust 6.3 Referral criteria An urgent referral should be made for any patient presenting with symptoms or signs of penile cancer. These include progressive ulceration or a mass in the glans or prepuce particularly, but can involve the skin of the penile shaft. Lumps within the corpora cavernosa not involving penile skin are usually not cancer but indicate Peyronie s disease, which does not require urgent referral. 6.4 Multi-Disciplinary Team Meetings (MDT/MDM) The SWAG Network Uro-Oncology MDT has been meeting weekly in Southmead Hospital every Wednesday afternoon, with attendance from all the urology clinicians from the six Acute Trusts around the Network and a full complement of other key MDT members, including oncologists, pathologists, radiologists, specialist nurses etc. There are Network cases discussed at this meeting (100% of appropriate cancer diagnosis) every week with approximately 30 new penile cases discussed per year in a supra-network setting. 6.5 Communication with local and diagnostic teams The MDT outcome proforma will be faxed back to the referring team with outcome and plans/recommendations. In addition, where patients are seen and assessed for supranetwork treatment in the joint clinic, a more detailed letter copied to the GP will follow the proforma. It is intended that there will be an opportunity on an annual basis for the supranetwork team to meet with those members of the referring teams who deal with penile cancer to discuss and feedback on issues relating to diagnosis, workup, management, outcome, and operation of the Network, as well as audit of patients referred. 6.6 Local specialist teams for counselling and carrying out non-supra- network procedures/treatments The Network have agreed a list of specialist teams for the Network who may counsel patients in order for them to select their primary treatment option from curative surgery, curative radiotherapy or other options. Table 7: Page 32 of 55

33 Trust Surgeon(s) Oncologist NBT David Dickerson/Ed Rowe Amit Bahl YDH RUH TST Christopher Parker, Tim Porter Christopher Gallegos, Ruaraidh, MacDonagh, Tim Porter Hugh Newman, Mark Beresford John Graham WAHT David Dickerson Serena Hilman Cheltenham David Jones Gloucester Hugh Gilbert Table 8: Extended team Mr Tim Burge Plastic Surgeon North Bristol Trust Mr Alan Kay Plastic Surgeon North Bristol Trust Mr John Palmer Dr Giles Dunnel Dr David DeBerker Plastic Surgeon Consultant Dermatologist Consultant Dermatologist Royal Devon and Exeter North Bristol Trust Host Centre Consultant Consultant in Palliative care Page 33 of 55

34 TBC Psycho-sexual Counsellor 6.7 Core team members to present options to patients The core team members from the supranetwork penile cancer team who will present the options for curative surgery, curative radiotherapy or other options are: David Dickerson (Surgeon) Amit Bahl (Oncologist) Catherine Hurd (CNS). The patients who will require counselling on options from the core team members will be seen at the joint clinic at the specialist Urology Centre in North Bristol Trust. The sites which will deliver a radiotherapy and chemotherapy service are the Bristol Hematology and Chemotherapy Service in Bristol and the Royal United Hospital in Bath. Chemotherapy only can be delivered in Weston Area Health Trust and Taunton and Somerset NHS Trust. Communication with referring Networks and General Practitioners: The MDT outcome proforma is faxed back to the referring team within 24hrs. Where appropriate a detailed letter will follow the proforma with a copy sent to the patients General Practitioner. Shared Care arrangements with referring Networks: Shared care arrangements are mutually agreed on a case by case basis by the referring and supra-network teams, and as outlined under 1.9 diagnosis and assessment below. 6.8 Facilities for patients The Supra-Network centre for penile cancers at Southmead Hospital is equipped and staffed appropriately to provide the following: Dedicated Urology outpatients department with access to penile specialist and core team members Dedicated Urology wards Dedicated Urology theatres Urology oncology clinical nurse specialists Lymphoedema service. 6.9 Waiting times position Currently, there is a weekly core member MDT meeting and all referrals are reviewed at the next MDT after receipt of the referral. Relevant histology specimens and imaging will be discussed and, where necessary, patients will be offered an appointment at the joint clinic after the MDT for assessment and to discuss and Page 34 of 55

35 arrange supranetwork care. Treatment recommendations will be made to the referring MDT where treatment can be carried out locally. There is a weekly operating list at Southmead Hospital to accommodate appropriate cases, and the aim is to offer a date for surgery within national cancer waiting times standards, especially when the clinical situation requires more urgent intervention, unless patients request a later date (if clinically acceptable) Diagnosis and assessment Patients should be referred under the two-week rule to their local urology department for initial diagnosis and assessment, and each new case should be reviewed by the supranetwork MDT. Following referral the network MDT will review all pathology. Those cases likely to require organ preserving treatment, reconstruction, node clearance surgery or complex adjuvant therapy should be assessed and where appropriate treated by this team. Other forms of treatment (partial or total penectomy, radiotherapy, or chemotherapy) may be carried out by other (local referring) specialist urological cancer teams which do not specialise in penile cancer. The penile cancer supranetwork MDT which reviews the case and makes treatment recommendations remains responsible for the overall management of the case Guidelines on Diagnosis of Penile Cancer TNM Classification The 2009 TNM classification for penile cancer (1) stratifies the T1 category into two prognostically different risk groups depending on whether lymphovascular invasion is present or not, or depending on grading (table 4). In addition, a subclassification of the T2 category regarding invasion of the corpus spongiosum only or the corpora cavernosa as well would be desirable, as it has been shown that the prognosis for corpus spongiosum invasion only is much better than for corpora cavernosa invasion (2, 3). It is important that the 2009 TNM classification includes any inguinal lymph node metastasis with extracapsular extension as pn3 recognising the significant adverse effect of extracapsular spread on prognosis (1).Retroperitoneal lymph node metastases are classified as extraregional nodal and therefore distant metastases which corresponds to the clinical course of the disease. TNM clinical and pathological classification of penile cancer (1), Table 10: Clinical classification T - Primary Tumour TX Primary tumour cannot be assessed T0 No evidence of primary tumour Tis Carcinoma in situ Ta Non-invasive carcinoma T1 Tumour invades subepithelial connective tissue Page 35 of 55

36 T1a Tumour invades subepithelial connective tissue without lymphovascular invasion and is not poorly differentiated or undifferentiated (T1G1-2) T1b Tumour invades subepithelial connective tissue with lymphovascular invasion or is poorly differentiated or undifferentiated (T1G3-4) T2 Tumour invades corpus spongiosum and/or corpora cavernosa T3 Tumour invades urethra T4 Tumour invades other adjacent structures N - Regional Lymph Nodes NX Regional lymph nodes cannot be assessed N0 No palpable or visibly enlarged inguinal lymph node N1 Palpable mobile unilateral inguinal lymph node N2 Palpable mobile multiple unilateral or bilateral inguinal lymph nodes N3 Fixed inguinal nodal mass or pelvic lymphadenopathy, unilateral or bilateral M - Distant Metastasis M0 No distant metastasis M1 Distant metastasis Pathological classification The pt categories correspond to the clinical T categories. The pn categories are based upon biopsy or surgical excision. pn - Regional Lymph Nodes pnx Regional lymph nodes cannot be assessed pn0 No regional lymph node metastasis pn1 Intranodal metastasis in a single inguinal lymph node pn2 Metastasis in multiple or bilateral inguinal lymph nodes pn3 Metastasis in pelvic lymph node(s), unilateral or bilateral or extranodal extension of any regional lymph node metastasis pm - Distant Metastasis pm0 No distant metastasis pm1 Distant metastasis G - Histopathological Grading GX Grade of differentiation cannot be assessed G1 Well differentiated Page 36 of 55

37 G2 Moderately differentiated G3-4 Poorly differentiated/undifferentiated Primary Lesion Detailed physical examination of the penis noting the size, nature and position of the primary tumour, if this is possible. A deep biopsy of the lesion is advisable (in cases where there is a tight phimosis a dorsal slit may be necessary to perform this). Cytological scrapings are usually inadequate and under-stage the disease. Ultrasound and MRI scanning of the penis have been used for staging but the role has not been fully established and should be considered optional. Premalignant penile lesions (precursor lesions) Lesions sporadically associated with SCC of the penis: Cutaneous horn of the penis Bowenoid papulosis of the penis Lichen sclerosus (balanitis xerotica obliterans) Premalignant lesions (up to one-third transform to invasive SCC): Intraepithelial neoplasia grade III Giant condylomata (Buschke-Löwenstein) Erythroplasia of Queyrat Bowen s disease Paget s disease (intradermal ADK) Regional Nodes Careful palpation of both groins for the detection of enlarged lymph nodes must be part of the initial physical examination of patients with penile cancer. a) Clinically negative (impalpable nodes). In the absence of palpable abnormalities, the likelihood of micro-metastasis is about 20%, however current imaging techniques are unreliable in in detecting these. Further diagnostic management of patients with impalpable lymph nodes should be guided by pathological risk factors. Lymphovascular invasion, local stage and tumour grade are risk factors for predicting the likelihood of lymphatic metastases. Invasive lymph node staging should be considered in patients at intermediate or high risk of lymphatic spread. b) Clinically positive (palpable nodes) Palpable lymph nodes are highly suspicious for the presence of lymph node metastases. Physical examination Page 37 of 55

38 should note the number of palpable nodes on each side and whether these are fixed or mobile. Additional inguinal imaging does not alter management and is usually not required. A pelvic CT scan can be performed in order to assess the pelvic lymph nodes. 18FDG-PET/CT has been reported to have a high sensitivity of % with a specificity of % for confirming metastatic nodes in patients with palpable inguinal lymph nodes (8,11) Guidelines on the Treatment of Penile Cancer Treatment of the Primary Lesion The aims of the treatment of the primary penile cancer lesion are complete tumour removal with as much organ preservation as possible, while radicality of the treatment should not be compromised. A local recurrence in itself has little influence on long-term survival so that organ preservation strategies are justified. Penile preservation appears to be superior in functional and cosmetic outcomes and should be offered as the primary treatment modality to men with localised penile cancer. However, there are no randomized studies comparing organ-preserving and ablative treatment strategies. There are only retrospective studies with a level of evidence of 3 or less. Histological diagnosis with local staging must be obtained in all cases, especially if non-surgical treatment modalities are considered. The treatment of the primary tumour and that of the regional nodes can be done as staged procedures. In both cases, it is essential to remove all malignant tissue with negative surgical margins. Patients should be counselled about all relevant treatment modalities. There are a variety of local treatment modalities for small and localized penile cancer including excisional surgery, external beam radiotherapy, brachytherapy and laser ablation which are used to treat localized invasive disease Treatment of superficial non-invasive disease (Tis/CIS) For penile CIS, topical chemotherapy with imiquimod or 5-FU is an effective first-line treatment. Toxicity and adverse events of these topical treatments are relatively low but the efficacy is limited. Complete responses have been reported in up to 57% of cases of CIS. For the reason of a high rate of persistence and/or recurrence, close and long-term surveillance of such patients is required. If topical treatment fails it should not be repeated. Laser treatment can be used for CIS. Photodynamic control may be used in conjunction with CO2 laser treatment. Alternatively, total or partial glans resurfacing can be offered as a primary treatment modality for CIS, and as a secondary treatment in case of treatment failure with topical chemotherapy or laser therapy. Glans resurfacing is a surgical technique which consists of complete abrasion of the glandular epithelium with covering by a split skin graft. With glans resurfacing for presumed non-invasive disease, up to 20% of patients Page 38 of 55

39 are found to have superficial invasive disease Treatment of invasive disease confined to the glans (Ta/T1a) For small and localized invasive lesions penile preserving treatment is recommended. Prior to conservative treatment modalities, it is mandatory to obtain histopathological diagnosis by biopsy. All patients must be circumcised before considering conservative non-surgical treatment modalities. For tumours confined to the prepuce, radical circumcision alone may be curative, if negative surgical margins are confirmed by definitive histology. For all surgical treatment options, the intra-operative assessment of surgical margins by frozen section should be considered as tumour-positive margins lead to local recurrence. Total removal of the glans (glansectomy) and prepuce does have the lowest recurrence rate among the treatment modalities for small penile lesions (2%). Negative surgical margins are imperative when using penile-conserving treatments and a margin of 5 mm is considered oncologically safe. Treatment choice should depend on tumour size, histology including stage and grade, localization especially relative to the meatus, as well as patient preference as there are no documented differences in the long term local recurrence rates between surgery, laser and radiation therapy Treatment of invasive disease confined to the corpus spongiosum/glans (T2) Total glansectomy, with or without resurfacing of the corporeal heads, is recommended Radiotherapy is an option Partial amputation should be considered in patients who are unfit for reconstructive surgery Treatment of disease invading the corpora cavernosa and/or urethra (category T2/T3) Larger distal tumours invading the glans and/or corporal heads can be managed with penile preserving surgery in most cases. Frozen section analysis of the margins of the resection are mandatory. Partial amputation with a tumour-free margin +/- reconstruction is standard treatment. A surgical margin of 5 mm is considered safe but patients should remain under close follow-up. Radiotherapy is an option Treatment of locally advanced disease invading adjacent structures (T3/T4) These are relatively rare (Europe 5%, Brazil 13%) (6). Total penectomy with perineal urethrostomy is standard surgical treatment for T3 tumours. In more advanced disease (T4) neoadjuvant chemotherapy may be advisable, followed by surgery in responders as in the treatment of patients with fixed enlarged inguinal nodes. Otherwise, adjuvant chemotherapy or palliative radiotherapy may be an option Local recurrence after organ-conserving surgery A second organ-conserving procedure can be performed if there is no corpus cavernosum invasion. For large or high stage recurrence, partial or total amputation will be required. In patients undergoing Page 39 of 55

40 total/subtotal amputation a total phallic reconstruction may be offered Management of the Regional Nodes The development of lymphatic metastases in penile cancer follows some anatomic rules. The inguinal and the pelvic lymph nodes are the regional drainage system of the penis. The superficial and deep inguinal lymph nodes are thereby the first regional nodal group reached by lymphatic metastatic spread. Spread to the inguinal lymph nodes can be uni- or bilateral from any primary penile cancer. A single photon emission computed tomography (SPECT) study in penile cancer patients reported that all inguinal sentinel nodes were located in the superior and central inguinal zones, with most found in the medial superior zone. No lymphatic drainage was observed from the penis to the two inferior regions of the groin, and no direct drainage to the pelvic nodes was visualized. These findings confirm earlier studies. The second regional lymph node groups are the ipsilateral pelvic lymph nodes. Pelvic nodal disease does not seem to occur without ipsilateral inguinal lymph node metastasis, and cross-over metastatic spread from one inguinal side to the contralateral pelvic side has never been reported in penile cancer. Further metastatic lymph node spread from the pelvic nodes to para aortic and para caval nodes is outside the regional lymph node drainage system of the penis, and is therefore classified as systemic metastatic disease. The management of regional lymph nodes is decisive for long-term patient survival. Cure can be achieved in metastatic disease confined to the regional lymph nodes. Lymphadenectomy is the treatment of choice for patients with inguinal lymph node metastases but multimodal treatment combining surgery and chemotherapy is often indicated. Management of the regional lymph nodes should be stage-dependent: In clinically node-negative patients (cn0), there is a definite risk of micro-metastatic lymph node involvement in about 20% of cases which is related to local tumour stage and grade In clinically positive lymph nodes (cn1/cn2), metastatic disease is highly likely and no time should be wasted on antibiotic treatment before surgical treatment With enlarged/fixed inguinal lymph nodes (cn3), multimodal treatment by chemotherapy and surgery is indicated Capsular penetration and extranodal extension in lymph node metastasis even if present in only one node carries a high risk of progression and is classified as pn3 which also requires multimodal treatment Management of patients with clinically normal inguinal lymph nodes (cn0) Risk stratification for the management of patients with clinically normal lymph nodes depends on stage, grade and the presence or absence of lymphovascular invasion in the primary tumour. Tumours with low risk of metastatic disease are those with superficial penile cancer (pta, ptis) and low grade pt1 tumours represent a heterogeneous risk group: they can be considered low-risk if they are well differentiated (pt1g1), otherwise they represent an intermediate-risk group (pt1g2) or must be considered high risk (pt1g3) together with all higher stages. Page 40 of 55

41 Several studies have shown that early inguinal lymphadenectomy in clinically node-negative patients is far superior concerning long-term patient survival compared to therapeutic lymphadenectomy when regional nodal recurrence occurs. One prospective study comparing bilateral lymphadenectomy, radiotherapy and surveillance in clinically node-negative patients reported that 5-year overall survival was significantly better with inguinal lymphadenectomy compared to immediate inguinal radiotherapy or that observed with a surveillance strategy (74% vs 66% and 63%, respectively). a) Surveillance (Ta Gl, Tl Gl lesions) Surveillance for the management of regional lymph nodes carries the risk of regional recurrence arising later from existing micrometastatic disease. Patient survival is over 90% with early lymphadenectomy and below 40% with lymphadenectomy for regional recurrence later. This definite risk must be taken into account when considering surveillance and the patient should be informed about this. Surveillance can only be recommended in patients with ptis and pta penile cancer, and with the appropriate caveats in pt1g1 tumours. A prerequisite for surveillance is good patient information and compliance. Patients who are advised or elect surveillance are followed up two monthly for the first year, three monthly for the second year and four monthly for the third year. Surveillance includes physical examination and ultrasound or MRI examination with or without fine needle aspiration of the groins. b) Invasive nodal staging Staging of the inguinal lymph nodes in cn0 penile cancer requires an invasive procedure since all imaging techniques (ultrasound, CT, MRI) are unreliable in excluding small and micro-metastatic lymph node involvement. While CT criteria other than size have been defined for the retrospective detection of lymph node metastases, these have not been validated prospectively. Nomograms are unreliable as their ability to predict the likelihood of lymph node involvement does not exceed 80%. Fine needle aspiration cytology does not reliably exclude micrometastatic disease (low specificity). Therefore, the pathological risk factors have to be used to stratify node-negative patients. There are two invasive diagnostic procedures whose efficacy is evidence-based: modified inguinal lymphadenectomy and dynamic sentinel-node biopsy. Both are at present standard approaches for the invasive diagnosis of inguinal lymph nodes in node-negative patients. Modified inguinal lymphadenectomy (milnd) is the standard surgical approach in this situation and defines a limited template whereby the superficial inguinal lymph nodes from at least the central and both superior Daseler s zones are removed bilaterally and the greater saphenous vein is left in place Dynamic sentinel node biopsy (DSNB) is a technique based on the assumption that primary lymphatic drainage from a penile cancer goes to only one inguinal lymph node on each side which may however be in different locations based on individual anatomy. With both methods of invasive regional lymph node staging in cn0 patients, missing existing micrometastatic disease will lead to later regional recurrence with a dramatic deterioration in long-term survival. This false negative rate has been reported to be as high as 12-15% for the DSNB technique even Page 41 of 55

42 . in experienced centres. The false-negative rate of milnd is not known The risk of a false-negative result and its implications for the prognosis should be explained to the patient before deciding on which method to use If lymph node metastasis is found with either method, an ipsilateral radical inguinal lymphadenectomy is indicated Patients should be considered for modified radical inguinal node dissection based on their risk status Patients in whom MRI, ultrasound, FNA and/or dynamic sentinel lymph node study are positive undergo modified radical inguinal node dissection Management of patients with palpable inguinal nodes (cn1/cn2) With uni- or bilateral palpable inguinal lymph nodes (cn1/cn2), the likelihood is very high that metastatic lymph node disease is present. Therefore, the old clinical advice that antibiotic treatment should be given for several weeks because such lymph node enlargement might be related to infection no longer holds true. Instead, no time should be wasted with such unnecessary delays and appropriate oncological diagnosis and treatment should be undertaken before further metastatic spread occurs. In clinically doubtful cases, ultrasound-guided fine needle aspiration cytology can be an option. With palpably enlarged inguinal lymph nodes, additional staging investigations are not useful. Imaging by ultrasound, CT or MRI does not provide additional information about the inguinal lymph nodes except in very obese patients. However, CT or MRI can provide information about the pelvic nodal status. PET/CT can identify additional metastases in lymph-node positive patients. Dynamic sentinel node biopsy is not reliable in patients with palpably enlarged and suspicious inguinal lymph nodes and should not be used. Patients in whom any of the investigative tests are histologically positive should have a modified radical inguinal node dissection. a) Radical inguinal lymphadenectomy In clinically lymph-node positive patients, surgical staging by inguinal lymphadenectomy is indicated. Intraoperative frozen sections may be used to confirm lymph node metastasis in which case an ipsilateral radical inguinal lymphadenectomy is required. Radical inguinal lymphadenectomy carries a significant morbidity related to problems of lymph drainage from the legs and wound healing. While morbidity can be as high as 70%, with increased BMI and Sartorius muscle transposition being significant risk factors for complications. Therapeutic radical inguinal lymphadenectomy can be life-saving but it may be underused for fear of associated morbidity. The surgical technique should be meticulous regarding tissue handling: Additional measures counteracting postoperative lymphatic stasis and leakage such as stockings, inguinal pressure dressings or vacuum suction as well as prophylactic antibiotics can reduce postoperative morbidity. In advanced cases, reconstructive surgery is often necessary for primary wound closure. The feasibility of performing laparoscopic and robot-assisted inguinal lymphadenectomy has been reported by several groups. Whether this provides any advantage is unclear. Page 42 of 55

43 a) Pelvic lymphadenectomy Patients with positive pelvic nodes have a worse prognosis compared to patients with only inguinal nodal metastasis. In a study of 142 node positive patients the significant risk factors for pelvic nodal metastasis are the number of positive inguinal nodes (cut-off 3), the diameter of inguinal metastatic nodes (cut-off 30 mm) and the presence of extra nodal extension. The proportion of pelvic nodal metastases was 0% in cases without any of these risk factors, and 57.1% when all three risk factors were present.. For small volume disease consideration should be given for complete pelvic node dissection followed by adjuvant radiotherapy and chemotherapy. For patients with large volume disease at presentation, surgery is optional and consideration should be given for primary radio- chemotherapy. Ideally, chemotherapy should be offered within the context of a clinical trial. Pelvic lymphadenectomy may be performed simultaneously or as a secondary procedure following definitive histology. If bilateral pelvic dissection is indicated, it can be performed through a midline suprapubic extraperitoneal incision. It is important to avoid unnecessary delay if these procedures are indicated. N1 Disease Patients with a single positive node without extra-capsular extension should then be kept on surveillance. The role of CT/MRI scanning in follow up is currently being evaluated. N2 Disease Patients with a single positive node with extra-capsular extension should be offered adjuvant radiotherapy to the ipsilateral groin. Patients with multiple or bilateral superficial nodes should be considered for pelvic node dissection or adjuvant radiotherapy to the involved groin and pelvic sidewall. If two or more positive lymph nodes or one node with extracapsular extension (pn3) are found on one side, ipsilateral pelvic lymphadenectomy/radiotherapy is indicated. There is no direct lymphatic drainage from penile tumours to the pelvic lymph nodes, therefore pelvic LAD is not indicated if there is no involvement of inguinal nodes on that side. This recommendation is based on a study in which the rate of positive pelvic nodes was found to be 23% in cases with more than two positive inguinal nodes and 56% in those with more than three positive inguinal nodes, or if there was extracapsular involvement in at least one inguinal node. Chemotherapy should ideally be considered within a clinical trial Management of patients with fixed inguinal nodes (cn3) The presence of metastatic disease in these cases is beyond doubt. Additional diagnostic measures do not alter the immediate management but staging by thoracic, abdominal and pelvic CT scan is indicated in order to assess the presence of further pelvic nodal disease and systemic metastatic disease. Page 43 of 55

44 In clinically unequivocal cases, histological verification by biopsy is not required. In rare cases with reasonable doubt, an excisional or core needle biopsy may be done. These patients have a poor prognosis and are unlikely to be cured by surgery alone. Upfront surgery is not generally recommended as this is non-curative and also usually quite destructive. Multimodal treatment with neoadjuvant chemotherapy followed by radical lymphadenectomy or radiotherapy in clinically responsive cases is recommended. Responders to neoadjuvant chemotherapy with post-chemotherapy surgery have been reported to achieve long-term survival in 37% of cases. In some cases, there may be individualized reasons for upfront surgery followed by adjuvant treatment Management of lymph node recurrence Patients with regional recurrence after surveillance should be treated in the same way as patients with primary cn1 or cn2 disease. Patients with regional recurrence following negative invasive staging by DSNB or modified inguinal lymphadenectomy already have a disordered inguinal lymphatic drainage anatomy and must be considered at a high risk of irregular metastatic progression. Patients with inguinal nodal recurrence after therapeutic radical inguinal lymphadenectomy have been reported to have a 5-year cancer specific survival of 16%. There is no evidence for the best management in such cases but multimodal treatment with neoadjuvant and/or adjuvant chemotherapy after radical lymph node surgery is advised Delayed Presentation of Positive Groin Nodes In this situation ipsilateral modified inguinal node dissection is appropriate. Assessment of the contra-lateral groin is sensible but is usually not involved. The same subsequent management depends on the number of nodes affected Metastatic Disease Palliative chemotherapy can be helpful to slow the progression of metastatic disease. There is no specific regime, which is generally recognized Cis-platinum and 5 Fluro-urocil are used though use of newer chemotherapy agents is being considered. Pulmonary metastases are the commonest site and chest CT should be offered in following up high-risk patients. The most common site for metastases is in the chest and the chest CT scan is probably the best way to evaluate this Clinical Trials Currently there are no trials in penile cancer running at the Bristol Haematology and Oncology Centre Follow-up A post-surgical follow-up appointment may be offered at two to three weeks to check on progress, discuss Page 44 of 55

45 the definitive histology and to plan further treatment. Subsequent follow-up regime dependent on risk of developing lymph node metastases: Table 12: Low Risk Group Tis, Ta T1 G1-2 with no vascular invasion High Risk Group Any G3 T2-3 Vascular invasion YEAR 1 and 2 3 months months months 6 5+ Annually Annually 6.13 Operational policy for the Penile Cancer Supra- network Multidisciplinary Team Background This operational policy has been written to ensure that all members of the network/supra-network are aware of the purpose and organisation of the Supra-network Penile Cancer MDT and the scope of services offered by the multidisciplinary team at Southmead Hospital. The document has been written in accordance with the national manual of Cancer Services standards and aims to encourage best practice in the management of patients with penile cancer. Aims of the Operational Policy The aims are to ensure that all MDT members have a policy of agreed standards and process to provide quality care. The objectives of the MDT are: To ensure that designated specialists work effectively together in teams such that decisions regarding all aspects of patient care for individual patients are based on review, discussion and agreement by the MDT To ensure that all decisions regarding operational policies are multidisciplinary decisions To ensure that care is given according to recognised guidelines and targets (including guidelines for onward referrals) with appropriate information being collected to inform clinical decision-making and to support clinical governance/audit To ensure that mechanisms are in place to support entry of eligible patients are recruited into clinical trials, subject to patients giving fully informed consent. Membership and responsibilities The Supra-Network Penile Cancer MDT is based at North Bristol Trust Southmead Hospital Network Cancer Centre and is incorporated into the SWAG network and centre MDT providing care for all cases of penile ca. Page 45 of 55

46 from the local catchment as well as for the network and supra-network and currently receives referrals from the following Networks: SWAG Three Counties Network Peninsula Network 2.1 million population 1.3 million population 1.7 million population MDT Lead Clinician Lead Clinician for the Supra-network Penile Cancer MDT will, within the constraints of the resources available, endeavour to: Ensure the objectives of MDT working (as laid out in Manual of cancer Service Standards) are met Ensure that designated specialists work effectively together in teams such that decisions regarding all aspects of diagnosis, treatment and care of individual patients and decisions regarding the team s operational policies are multi-disciplinary decisions Ensure that care is given according to recognized guidelines (including guidelines for onward referrals) with appropriate information being collected to inform clinical decision-making and to support clinical governance/audit Ensure mechanisms are in place to support entry of eligible patients into clinical trials, subject to patients giving fully informed consent Take overall responsibility for ensuring that MDT meeting and team meet Peer Review Quality Measures Ensure that target of 100% is met for new penile cancer patients to be discussed at the MDT meeting is met Provide link to NSSG, either by attendance at meetings or by nominating another MDT member to attend Lead on, or nominate lead for service improvement Organise and chair annual meeting examining functioning of team and reviewing operational policies, and collate any activities that are required to ensure optimal functioning of the team (e.g. training for team members) Ensure that the outcomes of the meeting are clearly recorded and clinically validated and the appropriate data collection is supported Ensure targets of communicating MDT outcomes to referring team/clinician are met The development and co-ordination of the Supra-network Penile Cancer MDT and its activities. (Including the organisation of an annual meeting to review operational polices and team functionality, ensuring team attendance at meetings and maintaining effective multi-disciplinary working and decision-making processes) Ensure the MDT s activities are audited, case review is undertaken and the results documented. Meetings The Specialist Penile Cancer (SPC) / Supra-Network MDT meets weekly in Southmead Hospital / BUI every Wednesday afternoon with recorded attendance of the core/extended team members and urology clinicians from the 6 other Trusts around the Network and other key MDT members including oncologists, pathologists, radiologists specialist nurses etc Core members or their deputies should achieve > 50% attendance The MDT will be represented by a team member at > two thirds of the NSSG meetings Page 46 of 55

47 Attendance at MDT meetings will be audited annually and presented at the MDT AGM A record of the patients discussed, the source of the referral and the outcome of the discussion/treatment plan are kept and the outcome will be communicated to the referring clinician/team (proforma fax sheet). There are Network cases discussed at this meeting every week with approximately 30 new penile cases discussed per year. Referral of patients to MDT Referrals from within the Local Network and the Supra-network are made via: Faxed proforma to MDT co-ordinator (contact details, copy of proforma) Direct referral to core members of SPCMDT (letter, telephone) Are discussed at next scheduled MDT Meeting. Relevant radiological investigations and pathology specimens should accompany or follow the referral to enable full review Two week wait referrals are not usually received directly by the supra- network MDT, however new suspected penile cancer referrals to the host centre are offered appointments and seen in accordance with the host centre s TWW arrangements All new cases of penile cancer, recurrent disease, patients with Lymph node metastasis or those with high risk of lymph node metastasis should be discussed at the MDT All relevant scans/x-rays and Pathology slides should be reviewed at the MDT and management/follow up recommendations made as per agreed network guidelines, and where supra-network treatment is planned, the relevant scans/x-rays will be forwarded to the admission point Once decided, the management plan/outcome is fast tracked back to referring Team/Centre/Specialist (proforma fax back followed by letter) Where appropriate (i.e. supra-network care/assessment likely or necessary, e.g. Stage 1 penile cancer, recurrence or LN disease) the patient will be offered either a Joint Clinic appointment or meeting with any member of the MDT to be assessed and/or to discuss and arrange further diagnostic tests/treatment Surgical procedures designated as requiring supranetwork care will be carried out on the North Bristol Trust Southmead Hospital site and patients will be offered a choice of elective admission or treatment (outpatient) Dates at the consultation at which treatment is decided Where appropriate, patients may be referred to neighbouring or remote supranetworks or specialist centres (e.g. total penile reconstruction or where core member is unable to provide specific treatment at the due time owing to leave, illness etc. to Mr. David Ralph (London) or Mr. Aivar Bracka (Midlands) as per agreed referral guidelines. Patient Information The MDT will develop and provide written information to patients including: Disease specific information Contact information (patient self-help groups, key worker, hospital, access to MDT) Services information A template information sheet/booklet for use throughout the Supra- network will be developed. Network Guidelines and Audit Page 47 of 55

48 The MDT (supra-network) will meet annually to discuss/ develop/approve/agree: Guidelines (Network) including follow-up protocols Referral guidelines i.e. networks and supranetwork roles (i.e. who can do what, and the named referring teams) and referral to another team Minimum Data Set and who collects which portion (clerical (target times) and clinical). Currently the supra-network MDT uses the dataset (incorporated into the MDT proforma) as agreed and used by the NSSG Audit projects and feedback from completed audits (minuted) including cancer wait times and to be carried out by all MDTs (for Penile Cancer Site) in the Network The audited total number of annual penile cancer referrals and surgical procedures by individual surgeons will be reported and minuted at the AGM. Service Improvement MDT Lead is responsible for including service improvement into MDT function and AGM Process mapping covering key stages of the patient journey will be carried out annually and an action plan for service improvement produced for agreement and action by the MDT and NSSG service improvement leads Where necessary the service improvement lead will instigate a capacity/demand study to substantiate the service improvement action plan. 7. Appendices: 7.1 Appendix 1 Radiotherapy and Oncology Team for the Urology NSSG Dr Amit Bahl Consultant Clinical Oncologist UHB Dr Chris Parker, Consultant Clinical Oncologist, YDH Dr John Graham, Consultant Clinical Oncologist TST Dr Mark Beresford, Consultant Medical Oncologist, RUH Dr Serena Hillman, Consultant Oncologist, NBT Dr Hugh Newman, Consultant Clinical Oncologist, RUH Dr Olivera Frim, Consultant Oncologist, UH Bristol Dr Penny Kehagioglou, Consultant Oncologist, RUH Dr Mohini Varughese, Consultant Oncologist Dr Susie Masson, Consultant Oncologist, UH Bristol Dr Amarnath Challapalli, Consultant Clinical Oncologist, UH Bristol Dr Emma Gray, Consultant Oncologist TST. 7.2 Appendix 2 Page 48 of 55

49 Imaging Guidelines This guidance, proposed by the Network Imaging Group seeks to: Help SSGs, Trusts, disease site multidisciplinary teams and the network, to comply with IOG and QMs Provide a framework for the consistent approach to diagnosis, staging and surveillance - end post code variations in practice Assist radiology departments in controlling demand and managing capacity. Haematuria Diagnosis Macroscopic Microscopic - symptomatic (loin pain, frequency) Without infection, age > 50 Yrs Renal US and plain film or CTU + cystoscopy Flexible cystoscopy plus renal ultrasound Flexible cystoscopy plus renal ultrasound Bladder Cancers Staging Surveillance For patients deemed fit for radical surgery or other radical treatment CT thorax abdomen and pelvis Bone scan - If clinically indicated No routine imaging Kidney Cancers Diagnosis US Staging CT thorax and abdomen MR - If IVC invasion seen on CT to clarify Page 49 of 55

50 upper level Surveillance A. Post nephrectomy TCC B. Post nephrectomy Renal Cell Ca A1. CT upper abdomen and remaining kidney Perform at 6 months and at 3 years B1. CXR at 6/52 and 6/12 Then B2. CT abdomen at 1 year Surveillance B3. For T1 and T2: CXR 6 monthly for 3 years Then Yearly for 5 years B4. For T3 and T4 CXR and US 6 monthly for 3 years CT thorax and abdomen at 1 year and 3 years Then CXR yearly for 10 years B5. For partial nephrectomy CXR and US 6 monthly for 3 years and CT at 2 years. Then CXR and US yearly for 10 years Teratoma and Seminoma Diagnosis US Staging Surveillance A. TERATOMA: ONLY for patients who have a NEGATIVE pelvic staging CT B1. SEMINOMA: For patients who have received adjuvant treatment CT thorax abdomen and pelvis A. CT chest and abdo Performed at 3, 6, 9, 12 and 24 months B1. CXR Page 50 of 55

51 B2. SEMINOMA: For patients who have not received adjuvant treatment Performed 3 monthly for 1 st year and then 6 monthly to 5 years B. B2. CT abdomen Performed at 3, 6, 9, 12 and 24 months Prostate Cancer Diagnosis Only if fit for radical treatment or definite histological diagnosis needed US TRUS (8-10 biopsies in 4 pots - minimum standard) (Gold standard = 8-12 biopsies in 8-12 pots) Radical treatment being considered and/or any of the following: Staging above Gleeson 7 or MRI pelvis Bone scan PSA 10 or above Bilateral disease or if > 50% of biopsies taken are positive Surveillance No routine imaging Techniques Pelvis CT Abdomen +/- Oral and iv contrast 10/10 axial scans, 5/5 if multislice Page 51 of 55

52 Include liver Image on lung, mediastinal and abdominal windows MR Pelvis Axial T1 and T2 5 mm whole pelvis Axial T2 3 mm prostate Coronal T2 3 mm prostate Sagittal T2 4 mm whole pelvis Pathology Guidelines 7.3 Appendix 3 All tumour specimens will be handled and recorded in accordance with the Royal College of Pathologists minimum dataset for prostate Cancer histopathology reports, incorporating the TNM staging 7 edition (2009). The network guidelines for the examination and reporting of urological cancer specimens take into account the following publications: Minimum datasets for histopathology reporting of urological cancers. The Royal College of Pathologists. or TNM classification of malignant tumours (7th edition). UICC (2009) WHO Classification of Tumours. Pathology and Genetics of tumours of the urinary system and male genital organs. IARC Press: Lyon The Pathologist plays a central role in the diagnosis and staging of urological cancers. The information in their reports can help in the planning of future treatment of the patient. All cancer cases should be reviewed by a cancer multi-disciplinary team, which has a Histopathologist as a core member. There should be a nominated lead pathologist for the service but all pathologists reporting urological cancer specimens should participate in the MDT meetings, in an appropriate EQA scheme and in local audit (including an assessment of consistency of reporting as appropriate to the site). Specimens should be reported within an agreed time frame to allow appropriate clinical decision making at a planned MDT meeting. Specimen Types: Page 52 of 55

53 Prostate: Core biopsies, TURP chippings, radical prostatectomies Bladder: Urine cytology, cystoscopic biopsies, cystectomies Ureter: Cystoscopic biopsies, cytology, nephrouretectomy Renal: Transcutaneous core biopsies, partial/complete nephrectomy Testis: Testicular biopsies, orchidectomy Penis: biopsy, partial/complete penectomies. Specimen examination: The local protocol for specimen examination should take into account national guidelines, and should be regularly reviewed and updated by the lead pathologists in consultation with other pathologists who participate in the service delivery. Grading and staging of urological tumours: Tumour grading: Prostate: Gleason scores should be given for all cancers (apart from those undergoing hormone/radiotherapy treatment as the Gleason score has been shown to be unreliable) Bladder/Ureter: The recent WHO grading system has not been widely accepted and it is advisable to continue using the 1973 system (Grades 1-3) in combination with the new system (if local clinicians request this) Renal: Clear cell tumours - Fuhrmann grading system (Grades 1-4) Testis: No grading is used Penis: Usually squamous cell carcinomas graded as well, moderate or poorly differentiated. Tumour staging: TNM classification of malignant tumours (7th edition). Use of ancillary laboratory techniques: All laboratories providing a pathology service in the network must have at least conditional CPA accreditation and ensure participation in an appropriate EQA programme, which demonstrates satisfactory laboratory performance. A wide range of immunohistochemical markers are available within the network. Those which are often used in the reporting of urological tumours include: High molecular weight cytokeratin (for basal cell layer marking in prostatic biopsies) P506S/AMACR (a marker highlighting prostatic adenocarcinomas) PSA (used to confirm prostatic origin) EMA, vimentin, AE 1/3 CK7 and CD117 (classification of renal tumours) Electron microscopy is also useful in differentiating renal oncocytomas from eosinophilic renal cell carcinomas Small biopsies sectioned at multiple levels should yield adequate numbers of spare sections to allow immunostaining of tumour if required It is advisable to keep immunospares on levels of prostatic cores as small atypical foci may not be represented in all levels. Page 53 of 55

54 Audit All pathologists reporting urological cancer specimens should participate in a relevant EQA scheme and local audits (including an assessment of consistency where more than one pathologist participates in service provision). The audits should include: Review of compliance with procedures for specimen examination and reporting Completeness of minimum datasets Diagnostic agreement/disagreement during review of cases for MDTs Review of diagnostic consistency between pathologists using data from cases in EQA circulation or blind circulations. The results of the audit process should be discussed with all pathologists who participate in service delivery. Referral for review or specialist opinion: NICE recommends that diagnostic biopsies are reviewed in the hospital where any definitive surgery is to be carried out. Minimum dataset for reporting: These are based on the minimum dataset for histopathology reports as published by the Royal College of Pathologists ( These have recently been updated and the prostate datasets are due to be published shortly. Prostate (published 2009, shortly to be updated) Bladder biopsy (April 2013) Cystectomy (April 2013) Adult kidney (Nov 2006 due to be updated) Renal pelvis (April 2013) Urethra (Update out for consultation) Testis (May 2014) Penis (Update out for consultation) Urinary tract and testis Adult kidney (Nov 2006) Penis (Nov 2006) Prostate (Oct 2009) Testis (May 2014) Urinary collecting system (Apr 2013) Page 54 of 55

55 7.4 Appendix 4 -END- Page 55 of 55