NICaN Testicular Germ Cell Tumours SACT protocols

Transcription

1 Reference No: Title: Author(s) Ownership: Approval by: Systemic Anti-Cancer Therapy (SACT) Guidelines for Germ Cell Tumours Dr Audrey Fenton Consultant Medical Oncologist, Dr Vicky Coyle Consultant Medical Oncologist & Dr Bode Oladipo Consultant Medical Oncologist NICaN NICaN Drugs and Therapeutics Committee Approval date: (30/06/16) Operational Date: July 2016 Version No. 3.0 Supercedes 2.0 Links to other policies Next Review: NICaN Testicular Germ Cell Tumours SACT protocols July 2018 Date Version Author Comments September 2011 V1 Dr A Fenton, Dr V Coyle November 2013 V2 Dr A Fenton, Dr V Coyle Gemcitabine oxaliplatin as a palliative treatment for platinum refractory disease added. Endorsed by Health & Social Care Board (HSCB) February 2016 V3 Dr A Fenton, Dr V Coyle, Dr B Oladipo Section on Surveillance included. VeIP regimen added. Page 1 of 10

2 Authorisation of Systemic Anti-Cancer Treatment (SACT) for Germ Cell Tumours Page 2 of 10

3 Staging and risk assessment: Baseline investigations: Routine bloods (FBC, oncology profile) AFP, HCG, LDH both pre-operative values and postoperative values (minimum 7 days post-operatively) Baseline staging CT scan (chest/abdo/pelvis) CT/MRI brain if very high serum HCG/extensive metastatic disease Weekly tumour markers (if raised) to ensure decrease and normalisation if no evidence metastatic disease on baseline CT scan Borderline lymphadenopathy on baseline CT scan and normal markers then consider the following prior to making definitive management plan: o short interval CT scan (at 6 weeks) o PET scan o biopsy Consideration of contralateral testicular biopsy (see follow-up guidelines) Pre-chemotherapy investigations include EDTA clearance before carboplatin or if history of impaired renal function; audiometry before platinum-containing regimens; pulmonary function tests before bleomycincontaining treatment; sperm banking before all chemotherapy (must do viral testing (Hep B & C, HIV (must include Hep B core as well as surface antigen) before arranging sperm banking). Staging and risk groupings: Marsden stage I Confined to testis (IM if raised markers) II A <2cm Infradiaphragmatic lymphadenopathy B 2-5cm C >5cm III A, B, C as above Supradiaphragmatic and infradiaphragmatic lymphadenopathy IV Disseminated disease (lungs, liver, bone) Page 3 of 10

4 IGCCCG criteria Histology NSGCT Prognostic category Good risk Intermediate risk Poor risk Clinical factors Testes/retroperitoneal primary; non-pulmonary visceral metastases; low markers Testes/retroperitoneal primary; no non-pulmonary visceral metastases; intermediate markers Mediastinal primary; nonpulmonary visceral metastases; high markers Markers AFP<1000 HCG<5000 LDH<1.5xULN AFP HCG LDH xULN AFP>10000 HCG>50000 LDH>10 xuln Seminoma Good risk Intermediate risk Testes/retroperitoneal primary; no non-pulmonary visceral metastases Testes/retroperitoneal primary; non-pulmonary visceral metastases Normal AFP Any HCG Any LDH Normal AFP Any HCG Any LDH Page 4 of 10

5 SEMINOMA Stage I seminoma Low risk Stage I seminoma No adverse prognostic features: o Tumour<4cm o No rete testis involvement Active surveillance is standard management option of patients with low-risk Stage I seminoma. Reported relapse rates are <12% in this group, with the majority of relapses occurring in the first two years of follow-up and paraaortic nodes the most common site of relapse. High risk Stage I seminoma Adverse prognostic features: o Tumour>4cm o Rete testis involvement These features are independent prognostic factors identified from surveillance studies, with relapse rates of up to 32% if both features are present. Patients with risk factors are offered adjuvant therapy, particularly if both poor prognostic factors are present Adjuvant treatment options: o Single cycle carboplatin AUC7 (preferred option in NICC) o Paraaortic radiotherapy (Para-aortic strip 20Gy/10#/2weeks) Relapse rates are similar for either strategy (3-4%) but carboplatin is a more practical alternative and is also associated with a lower risk of contralateral testis tumours. There is a risk of malignancy with paraaortic radiotherapy. Paraaortic nodes are the commonest site of relapse after carboplatin, but rarely after radiotherapy. Page 5 of 10

6 Stage II-IV seminoma Seminoma Stage IIA/IIB Treatment options: o Paraaortic and ipsilateral iliac radiotherapy (30 Gy/15#/3 weeks) for patients with stage IIA or IIB disease that can be encompassed within a RT field o Marsden protocol single cycle carboplatin AUC7 followed 4 weeks later by paraaortic radiotherapy (30Gy/15#) Seminoma Stage IIB (large volume) - IV Standard treatment is chemotherapy: o 3 cycles BEP o 4 cycles EP These regimens are of comparable efficacy in good prognosis patients; 4 cycles of EP should be considered in patients at risk of bleomycin lung toxicity (older age, smoking history, history of lung disease) Tumour markers should be checked weekly during treatment CT scan should be performed on completion of treatment o If no residual mass patients should enter surveillance directly (see follow-up guidelines) o Residual masses <3cm should have follow-up imaging as outlined in the follow-up guidelines o Residual mass >3cm PET scan should be performed 4-6 weeks after last cycle of chemotherapy. If negative then patients can enter surveillance directly. If positive then surgical resection or a biospy may be considered. Note resection of post-chemotherapy masses in seminoma is a high risk procedure with increased risk of operative complications from dense tissue fibrosis. Page 6 of 10

7 Relapsed seminoma: Stage I disease: o Limited locoregional relapse radiotherapy and/or chemotherapy as per stage IIA/IIB primary disease o Extensive locoregional relapse or metastatic disease chemotherapy (BEP or EP) Stage II IV disease: o Progressive disease after first-line chemotherapy should be confirmed histologically in the absence of tumour marker elevation, and treated with salvage chemotherapy (TIP) Late relapse (>2 years after completion of first line therapy) Primary management is surgical resection if feasible If surgical resection not feasible, disease should be confirmed histologically and treated with salvage chemotherapy (TIP) If evidence of response to chemotherapy, consider surgical resection of residual masses. NON-SEMINOMA Stage I non-seminoma Low risk Stage I non-seminoma No evidence of lymphovascular invasion Active surveillance is standard management option of patients with low-risk Stage I teratoma. Reported relapse rates are 15-20% in this group, with the majority of relapses occurring in the first two years of follow-up. The most common site is retroperitoneal nodes. High risk Stage I non-seminoma Lymphovascular invasion is the most important prognostic factor for relapse and associated with relapse rates of around 50%. Standard management is two cycles of adjuvant BEP chemotherapy (low dose etoposide). The use of a single cycle of BEP is under investigation. Page 7 of 10

8 Surveillance can be considered but the risk of relapse and need for more intensive chemotherapy must be fully discussed Overall outcomes are similar for both management options Stage IM-IV non-seminoma Specific treatment depends on prognostic classification but in broad terms comprises primary chemotherapy followed by surgery. Good prognosis group: o 3 cycles BEP chemotherapy (3 or 5 day schedule) o 4 cycles of EP can be considered if risk of bleomycin lung toxicity Intermediate/poor prognosis group: o 4 cycles BEP chemotherapy (5 day schedule) Tumour markers should be checked weekly during treatment and after treatment pending restaging scan or surgical resection. CT scan should be performed on completion of treatment o Residual mass >1cm resection of residual masses should be performed. o Tumour markers should be checked weekly while awaiting surgery o Consolidation chemotherapy can be considered if evidence of >10% viable tumour in resected masses (2 cycles VIP) Relapsed non-seminoma: Patients on surveillance after surgery alone who relapse should receive chemotherapy as described above. The long term prognosis of these patients is very good. Progressive disease after first-line chemotherapy should be treated with salvage chemotherapy (TIP preferred option). Consider referral of patients with rapid platinum-refractory relapse and poor prognosis to a supra-regional specialist centre for consideration of high dose chemotherapy and stem cell transplantation. Resection of residual masses after salvage chemotherapy should be considered. Page 8 of 10

9 Late relapse (>2 years after completion of first line therapy) o Primary management is surgical resection if feasible o If surgical resection not feasible, disease should be confirmed histologically and treated with salvage chemotherapy (TIP preferred option) o If evidence of response to chemotherapy, consider surgical resection of residual masses. Consider referral of patients with relapsed after first and second line therapy disease to a supra-regional specialist centre for consideration of high dose chemotherapy and stem cell transplantation, if performance status 0 or 1. Gemcitabine/oxaliplatin can be considered as palliative treatment for patients with platinum-refractory disease. Surveillance All patients should be placed on an individualized surveillance schedule, according to the prior treatment received. This comprises mainly of regular CT or MRI scans, tumour markers monitoring, and clinical assessments, and is outlined in the separate Follow up guidelines for Testicular Cancer document. Patients considered to be at high risk of a contralateral testicular primary cancer should also be offered annual USS of the remaining testis. This high risk population includes patients any of the following: -History of testicular maldescent. -Microcalicfication or microlithiasis in the remaining testis -Infertility -Small volume or atrophic testis -Diagnosed with testicular seminoma at age < 30 years If there is uncertainty regarding the presence of risk factors on the patient s baseline ultrasound a repeat should be requested at one year to specifically clarify testicular volume and presence/absence of microlithiasis. For patients with any risk factor present yearly ultrasound of contralateral testis until aged 55 or beyond if still on 10 years follow up. Page 9 of 10

10 Appendix A: Chemotherapy regimens Carboplatin AUC7 (adjuvant) Carboplatin AUC7 on day 1 only EP (2 day platinum): Cisplatin 50mg/m2 days 1 & 2. Etoposide 165mg/m2 days 1, 2 & 3. EP (5 day platinum): Cisplatin 20mg/m2 days 1 to 5. Etoposide 100mg/m2 days 1 to 5. BEP (adjuvant low dose etoposide): Cisplatin 50mg/m2 days 1 & 2 Etoposide 120mg/m2 days 1, 2 & 3 Bleomycin IU on days 2, 9 & 16 BEP (metastatic 2 day platinum): Cisplatin 50mg/m2 iv infusion days 1 & 2 Etoposide 165mg/m2 days 1, 2 & 3. Bleomycin IU on days 2, 9 & 16 BEP (metastatic - 5 day platinum): Cisplatin 20mg/m2 days 1 to 5. Etoposide 100mg/m2 days 1 to 5. Bleomycin IU on days 2, 9 & 16 TIP: Paclitaxel 175mg/m2 day 1. Cisplatin 20mg/m2 days 1 to 5. Ifosfamide 1000mg/m2 & Mesna 500mg/m2 days 1-5. VeIP: Vinblastine 0.11mg/kg days 1 & 2. Cisplatin 20mg/m2 days 1 to 5. Mesna 120mg/m2 prior to Ifosfamide on day 1 only. Ifosfamide 1.2g/m2 & Mesna 1.2g/m2 days 1 to 5. VIP: Cisplatin 20mg/ m 2 days 1 to 5. Mesna 120mg/m 2 prior to Ifosfamide on day 1 only. Ifosfamide 1.2g/ m 2 & Mesna 1.2g/m2 days 1 to 5. Etoposide 75mg/ m 2 day 1 to 5 GEM-OX: Gemcitabine 1000mg/m2 day 1 and day 8 Oxaliplatin 130mg/m2 day 1. Page 10 of 10