Complex case Presentations

Case Presentations April 2016 Lisa M Pickering

Case presentations: chromophobe renal carcinoma 60 year old man. ECOG PS 0 No significant comorbodities August 2009: L radical nephrectomy Chromophobe renal cell carcinoma Sarcomatoid features G2 pt3an0m0 Leibovich score: 6 Adjuvant SORCE trial: (sorafenib 1 or 3 years v placebo)

Case presentations: chromophobe renal carcinoma One year later August 2010: Routine CT Retroperitoneal lymph node relapse Hb 109 g/l, Alb 27 g/l

Case presentations: chromophobe renal carcinoma One year later August 2010: Routine CT Retroperitoneal lymph node relapse Hb 109 g/l, Alb 27 g/l Resected 6/11 retroperitoneal LN positive for chromphobe RCC. No extracapsular spread Taken off trial SHOULD HE HAVE ANY FURTHER THERAPY? 1. Pazopanib 2. Sunitinib 3. Different systemic therapy 4. Radiotherapy 5. Surveillance

Panel discussion

Case presentations: chromophobe renal carcinoma One year later August 2010: Routine CT Retroperitoneal lymph node relapse Hb 109 g/l, Alb 27 g/l Resected 6/11 retroperitoneal LN positive for chromphobe RCC. No extracapsular spread Taken off trial WE CHOSE: 1. Pazopanib 2. Sunitinib 3. Different systemic therapy 4. Radiotherapy 5. Surveillance

Case presentations: chromophobe renal carcinoma Four years later (March 2014) Six months after previous CT scan Symptomatic dysphagia Mediastinal lymph node relapse Note: Four years to relapse despite apparent high risk features MANAGEMENT OPTIONS 1. Pazopanib 2. Sunitinib 3. Radiotherapy 4. Resection 5. Surveillance

Panel discussion Resectable Arguments to reseque?

Case presentations: chromophobe renal carcinoma Four years later (March 2014) Six months after previous CT scan Symptomatic dysphagia Mediastinal lymph node relapse Note: Four years to relapse despite apparent high risk features WE CHOSE: 1. Pazopanib 2. Sunitinib 3. Radiotherapy 4. Resection (Renal cell carcinoma) 5. Surveillance

Case presentations: chromophobe renal carcinoma 6 weeks later (May 2014) First surveillance scan after surgery No recurrence Does he need any further therapy? POSSIBLE OPTIONS 1. Pazopanib 2. Sunitinib 3. Other systemic therapy 4. Radiotherapy 5. Surveillance

Panel discussion

Case presentations: chromophobe renal carcinoma 6 weeks later (May 2014) First surveillance scan after surgery No recurrence Does he need any further therapy? WE CHOSE: 1. Pazopanib 2. Sunitinib 3. Other systemic therapy 4. Radiotherapy 5. Surveillance

Case presentations: chromophobe renal carcinoma Another 6 weeks later (July 2014) Dysphagia++ Repeat CT scan Mediastinal lymph node recurrence No other sites of disease

Case presentations: chromophobe renal carcinoma Another 6 weeks later (July 2014) Dysphagia++ Repeat CT scan Mediastinal lymph node recurrence No other sites of disease MANAGEMENT OPTIONS 1. Pazopanib 2. Sunitinib 3. Other systemic therapy 4. Radiotherapy 5. Re-resection

Panel discussion

Case presentations: chromophobe renal carcinoma Another 6 weeks later (July 2014) Dysphagia++ Repeat CT scan Mediastinal lymph node recurrence No other sites of disease WE CHOSE: 1. Pazopanib 2. Sunitinib 3. Other systemic therapy 4. Radiotherapy 5. Re-resection

Case presentations: chromophobe renal carcinoma 12 weeks later (October 2014) Clinically improved Repeat CT scan Mediastinal lymph node reduction

Case presentations: chromophobe renal carcinoma January 2015 Sunitinib 50mg 4 / 2 Ongoing symptomatic benefit Radiological: incremental response Toxicities from treatment: supportive measures insitgated POSSIBLE MANAGEMENT STRATEGIES 1. Dose reduction 2. Schedule alteration 3. Change to pazopanib 4. Change to axitinib 5. Surgery 6. Radiotherapy 7. Treatment interruption

Panel discussion

Case presentations: chromophobe renal carcinoma January 2015 Sunitinib 50mg 4 / 2 Ongoing symptomatic benefit Radiological: incremental response Toxicities from treatment: supportive measures insitgated WE CHOSE: 1. Dose reduction 2. Schedule alteration 3. Change to pazopanib 4. Change to axitinib 5. Surgery 6. Radiotherapy 7. Treatment interruption

Case presentations: chromophobe renal carcinoma By September 2015 Further clinically improvement Complete resolution of disease and no new sites Ongoing toxicities on 37.5mg 2/1

Case presentations: chromophobe renal carcinoma By September 2015 Further clinically improvement Complete resolution of disease and no new sites Ongoing toxicities on 37.5mg 2/1 OPTIONS 1. Dose reduction 2. Schedule alteration 3. Change to pazopanib 4. Change to axitinib 5. Surgery 6. Radiotherapy 7. Treatment interruption

Panel discussion

STAR Trial, UK CLRN Ph II/III RCT Controlled-trials.com ISRCTN 06473203 mrcc N = 1000 Clear cell predominant First line ECOG PS 0/1c R A N D O M I S E Sunitinib or Pazopanib Conventional Schedule Sunitinib or Pazopanib Interrupted Schedule 1 Endpoint: PFS 2 Endpoints: OS, ORR, duration of response, safety, QoL

Complex Case Discussion Axel Bex The Netherlands Cancer Institute Division of Surgical Oncology Urology Amsterdam, The Netherlands

Male, 64 years Previous history : DVT due to factor V Leiden disease 07/ 2008 Bilateral renal tumours considered sporadic given his age of 56 years at diagnosis and absent family history ct1b cn0 cm0 right kidney 4.5 cm located in mid to lower pole in the hilar area R.E.N.A.L. complexity score 8 (medium) ct1a cn0 left kidney 2.9 cm R.E.N.A.L. complexity score 5 (low)

Panel discussion Idea on diagnosis Biopsy? Which side to start with?

08/ 2008 after multidisciplinary tumour board Open partial nephrectomy right kidney with trial-based sentinel node and locoregional lymph node dissection and radiofrequency ablation (RFA) after biopsy of the left kidney pt1b pn0 cm0 clear-cell RCC Fuhrman grade 3 right kidney, margin microscopically positive Biopsy left kidney clear-cell RCC Fuhrman grade 3

10/2010 26 months after surgery Metachronous solitary lung metastasis and mediastinal lymph node ipsilateral pulmonary artery LN station 10

Panel discussion Need for biopsy? Surgery? Medical treatment?

10/2010 26 months after surgery Metachronous solitary lung metastasis and mediastinal lymph node ipsilateral pulmonary artery LN station 10 12/2010: metastasectomy of a 1.2 cm solitary clear-cell metastasis and hilar lymph node dissection with a single lymph node metastasis

01/2013 52 months after initial surgery 24 months after metastasectomy Suspected bilateral recurrence

Panel discussion Need for biopsy? Surgery? Medical treatment?

01/2013 52 months after initial surgery 24 months after metastasectomy Suspected bilateral recurrence Multidisciplinary decision to perform repartial nephrectomy on the right kidney and a percutaneous RFA left 03/2013: partial nephrectomy right kidney for a clear-cell recurrence, Fuhrman grade 2, margin positive!

Panel discussion What to do? Nephrectomy right kidney and RFA left kidney in a previously metastatic patient with high-risk of progression? Bilateral RFA?

Multidisciplinary tumour board What to do? Nephrectomy right kidney and RFA left kidney in a previously metastatic patient with high-risk of progression? Bilateral RFA? bilateral RFA

08/2015 56 months after previous (first) metastasectomy 23 months after RFA for local recurrences 0.8 cm new pulmonary lesion 10/2015: video assisted thoracoscopic metastasectomy (VATS) for a 6 mm clear-cell metastasis

01/2016 gross hematuria after exercise Multifocal contrast enhancing lesions in the rght renal pelvis, ureter and in the bladder at the orifice 02/2016 TUR-B and attempted ureterorenoscopy: clear-cell RCC

Next options? Locoregional recurrence 27 months after RFA for a previous local recurrence but only 5 months after last metastasectomy for distant disease CT chest and abdomen 04/2016: no evidence of further systemic disease. Serum creatinine 108 µmol/l, GFR (MDRD-4) 60 ml/min/1.7 Consider rapid progression and start systemic therapy? Nephroureterectomy for local control and delay of systemic therapy?

Panel discussion Please help Dr Bex.

Case Presentations April 2016 B Rini

RCC in a Solitary Kidney 60 year-old-man, ECOG 0 Congenital solitary left kidney PMH: Hypertension, controlled with medication to 130/85 mmhg; no other PMH Dec. 2009: 2 month history of painless hematuria 5 kg weight loss in the past month

RCC in a Solitary Kidney Abd-US: hypoechoic area (4 x 3 x 3.2 cm) within the left kidney CT-Scan: Abd: diffuse infiltrative mass (5 cm) involving the upper pole of the left kidney; renal vein thrombus, perinephric lymph nodes; Thorax: bilateral indeterminate 2-5 mm pulmonary nodules

Panel discussion 1) partial nephrectomy 2) kidney biopsy to confirm clear cell RCC, then neoadjuvant VEGFR TKI 3) radical nephrectomy + hemodialysis

RCC in a Solitary Kidney Renal biopsy -> clear cell carcinoma, Fuhrman grade 2/4 (March - July 2010) phase II clinical trial with sunitinib (Jul 10): PR with 30% volume reduction. No lung changes. (Jul 10): Surgery: Partial left nephrectomy + vein thrombectomy Pathology: clear cell histology, grade 2/4, pt3, neg. margins Post-Op complications: ARF + fluid overload (No HD required); ARF resolved

RCC in a Solitary Kidney Follow up 6 months (Jan 11) CT: 1.7 cm non-occlusive thrombus Left RV. Lung nodules stable

Panel discussion 1) thrombectomy 2) restart sunitinib 3) radical nephrectomy + hemodialysis

RCC in a Solitary Kidney (Mar 11) Surgery: tumor thrombus resection + RV replacement with tubularized pericardial graft (Jul 11) CT: Renal hilar, pelvis, RV and soft tissue infiltration with tumor recurrence. No disease elsewhere. No viable resection possible

RCC in a Solitary Kidney (Jul 11) Sunitinib 50mg PO (4/2 schedule) with mild treatment-related skin toxicity. (Dec 11): Stable Disease. Sunitinib alteration to 2/1 schedule due to grade 2-3 HFS. Hypertension medication adjustment. (June 14) Locoregional PD with Post-renal failure due to left ureteric obstruction Percutaneous nephrostomy tube placed.

Panel discussion 1) Switch to axitinib 2) radical nephrectomy + hemodialysis 3) Other

RCC in a Solitary Kidney (June 14) STOP Sunitinib. Start Axitinib 5 mg bid. (August 14) Last Visit Clinically well. ECOG 0-1 CT Scan: stable disease.

RCC in a Solitary Kidney June 14: Axitinib 5mg BID -> 6mg BID; well tolerated with initial regression. Oct 15: Pt with progression in kidney causing renal failure requiring dialysis. Only gross disease is in solitary remaining kidney

Panel discussion 1) Radical nephrectomy NED/dialysis 2) Change systemic therapy to nivolumab

RCC in a Solitary Kidney 11/24/2015: Left open radical nephrectomy, removal left JJ ureteral stent, RPLND pathology revealed 11cm clear cell renal cell carcinoma, grade 3/4, pt3an0mx with negative margins, two lymph nodes were negative. April 2016

Panel discussion Please help Dr Rini.

Case Presentations April 2016 JJ Patard

Case presentation: bilateral and multifocal renal tumors 56 yrs old man No personal medical past history No familial kidney disease past history Incidental diagnosis of bilateral renal tumors Normal chest CT scan

Case presentation: bilateral and multifocal renal tumors 1 large hyper vascular hilar tumor in the right kidney RENAL score 11p At least 2 tumors in the left kidney RENAL Score 6 a Serum creatinin: 0.80 mg/dl MDRD GFR: 100 ml/min

Panel discussion Clear cell RCC? Oncocytoma? Papillary RCC? Chromophobe carcinoma? Other?

Panel discussion Role of biopsy? Is it reliable in case of multiple tumors? Will it change surgical strategy? Once surgery is decided, what to do? Double left partial nephrectomy first? Right partial nephrectomy first? Right radical nephrectomy first?

Case presentation: bilateral and multifocal renal tumors In the real life, the patient underwent a left renal biopsy six month earlier Result: Oncocytoma, an expectant follow-up had been advised The tumors have grown and the patient is asking for a second medical opinion Question to the panel: is the previous diagnosis of oncocytoma going to change your surgical management?

bilateral and multifocal renal tumors, practical management We started by left partial nephrectomy There were indeed 5 renal tumors ++ All the tumors were excised with negative margins WIT: 25 minutes No significant post op morbidity Serum creatinine at discharge: 0.95 mg/dl (MDRD GFR: 82 ml/min) Panel discussion; the limits of pre op imaging in case of multiple small renal tumors

bilateral and multifocal renal tumors, histological results left side Tumor 1 Tumor 2 Tumor 3 Tumor 4 Final Histological pathology (Pr N Rioux Leclercq): hybrid tumor (oncocytoma + chromophobe carcinoma) Question to the panel: will it change your mind for right side management?

bilateral and multifocal renal tumors, right side management We decided a partial nephrectomy WIT 30 minutes Estimated Blood loss: 800 ml Non intra operative complications Day 1 Gross haematuria Malaise, tachycardia, Hb: 7 g/dl Peri renal drainage > 400 ml Questions to the panel: Immediate re operation for surgical haemostasis? Immediate total nephrectomy? CT +- embolization? Blood transfusion and expectant management?

bilateral and multifocal renal tumors, panel discussion: BHD syndrome

bilateral and multifocal renal tumors, panel discussion: BHD syndrome Oncocytic hybrid tumors 50% chromophobe RCCs 34% Clear cell RCCs 9% Oncocytomas 5% Papillary RCCs 2%