Management of Locally Reccurent Renal Cell Carcinoma Jose A. Karam, MD, FACS Assistant Professor Department of Urology
DefiniAons Defini&ve treatment Aiming for cure Abla&on therapy Radiofrequency abla&on Cryoabla&on Surgery (Open, Laparoscopic, or Robo&c) Par&al nephrectomy Radical nephrectomy
Local recurrence DefiniAons Recurrence of an already treated cancer Loca&on=retroperitoneum The kidney itself Where the kidney is/was (renal fossa) Adrenal gland (same side of the affected kidney) Lymph nodes (same side of the affected kidney)
How oden does a local recurrence happen? With abla&on therapy Less than 10% With par&al nephrectomy Around 5% With radical nephrectomy Less than 3%
How do we find a local recurrence? Rou&ne imaging aper treatment CT scan MRI Symptoms aper treatment Pain Bleeding Fa&gue Weight loss Mass
What to do ader discovery of local recurrence? Check for cancer in other areas Chest Xray or CT chest Careful review of the CT or MRI abdomen/pelvis MRI brain if indicated Bone scan if indicated Consider repeat imaging in 2-3 months if small Consider biopsy if indicated
Possible Scenarios? Local recurrence only (Best case scenario) Local recurrence + distant recurrence (metastasis)
Observa&on Abla&on Surgery Systemic therapy Treatment OpAons?
AUA guidelines EAU guidelines NCCN guidelines Guidelines? No recommenda&ons!!!
How do we decide what treatment? Pa&ent factors: Age Performance status Renal func&on Comorbidi&es Other cancers Wishes and expecta&ons Tumor factors: Size Loca&on Growth rate Biopsy result (if available)
Outline Recurrence aper abla&on Recurrence aper par&al nephrectomy Recurrence aper radical nephrectomy
1- RECURRENCE AFTER ABLATION THERAPY
Local Recurrence ader AblaAon
Local Recurrence ader AblaAon Abla&on is done à local recurrence is <5% of pa&ents Treatment op&ons Observa&on Repeat abla&on Surgery
Surgery For Local Recurrence ader AblaAon : NCI 2001-2007 13 pa&ents (VHL) All had prior radiofrequency abla&on (RFA) 16 par&al nephrectomies All had par&al nephrectomy Average number of tumors removed = 7 Average opera&ng &me ~ 8 hours Average blood loss = 1.5 liters Kowalczyk KJ. J Urol. 2009
Surgery For Local Recurrence ader AblaAon : CCF (Updated) 27 pa&ents (1997-2013) 9 had radiofrequency abla&on (RFA) 18 had cryoabla&on 14 par&al nephrectomy, 12 radical nephrectomy, 1 aborted surgery Median tumor size 3.6 cm Median blood loss ~ 225 ml Clavien III-IV complica&ons 6 (22%) Follow up (median 14.5 months): NED- 67% Recurrence- 8% Lost to follow-up- 25% Jimenez J. J Urol. 2016
Surgery For Local Recurrence ader AblaAon: MD Anderson Experience 2006-2013 14 pa&ents 10 had radiofrequency abla&on (RFA) 4 had cryoabla&on Surgery done ~ 2 years aper abla&on 11 par&al nephrectomy 3 radical nephrectomy Karam JA. BJU Int. 2014
Surgery For Local Recurrence ader AblaAon: MD Anderson Experience Median age at surgery = 65 years Median surgery dura&on ~ 3.5 hours Median blood loss ~275 ml Median size of tumor = 3.1 cm Major complica&ons = 4 pa&ents (all recovered) 1 recurrence only (Pa&ent with VHL) Karam JA. BJU Int. 2014
Local Recurrence ader AblaAon Treatment -Open par&al nephrectomy -Clamp &me = 8 minutes -pt1a (3.8cm) -Clear cell RCC -Grade 2 -Nega&ve margins -NED 38 months postop
2- RECURRENCE AFTER PARTIAL NEPHRECTOMY
Local Recurrence ader ParAal Nephrectomy
Local Recurrence ader ParAal Nephrectomy Incidence ~5% Loca&on Kidney itself-same area of prior treated tumor Kidney itself-different area Around the kidney/lymph nodes/adrenal gland
Local Recurrence ader ParAal Nephrectomy: Mayo Clinic 2003-2012 Pa&ents had prior par&al nephrectomy 48 pa&ents with 68 tumors All local recurrences were treated with cryoabla&on Average tumor size 2.5cm Major complica&ons = 5.7% Average follow up &me = 1.5 years Another recurrence = 9.3% Hegg RM. J Urol. 2013
Local Recurrence ader ParAal Nephrectomy: NCI 1992-2006 Pa&ents (with VHL) had prior par&al nephrectomy 47 pa&ents All local recurrences were treated with repeat par&al nephrectomy Surgery &me = 7.5 hours Blood loss = 1.8 liters Average number of tumors removed = 7 Average size of largest tumor removed = 3.5cm Johnson A. J Urol. 2008
Local Recurrence ader ParAal Nephrectomy: NCI Major complica&ons = 19.6% 3 pa&ents required radical nephrectomy Postopera&ve death = 1 pa&ent Average follow up &me ~5 years Another recurrence that needed surgery= 19.6% 46 pa&ents were s&ll alive Johnson A. J Urol. 2008
Local Recurrence ader ParAal Nephrectomy: MD Anderson 44 pa&ents with local recurrence aper PN 163 controls (no recurrence) Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Pathologic Stage at ini&al par&al nephrectomy pt1a = 20 (40.8%) pt1b = 13 (26.5%) pt3a = 7 (14.2%) pt3b = 3 (6.1%) Histology at ini&al par&al nephrectomy Clear cell = 41 (93.2%) Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability 0.0 0.2 0.4 0.6 0.8 1.0 Surgical Margin Negative (n=193) Positive (n=12) Logrank P-value<0.01 0 2 4 6 8 10 12 14 No. at Risk Negative Positive 193 12 143 5 91 4 52 4 Time (year) 27 2 16 0 6 0 0 0 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability 0.0 0.2 0.4 0.6 0.8 1.0 Under 6 (n=56) 7-9 (n=118) 10-12 (n=16) Logrank P-value<0.01 0 2 4 6 8 10 12 14 No. at Risk Under 6 7-9 10 56 118 16 46 83 9 34 48 3 21 27 2 Time (year) 9 14 0 5 7 0 3 1 0 0 0 0 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability 0.0 0.2 0.4 0.6 0.8 1.0 1 (n=151) 2 (n=15) >2 (n=14) Logrank P-value<0.01 0 2 4 6 8 10 12 14 No. at Risk 1 2 >2 151 15 14 111 9 9 83 6 3 50 4 1 Time (year) 26 2 0 15 1 0 6 0 0 0 0 0 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability 0.0 0.2 0.4 0.6 0.8 1.0 T1a+T1b (n=191) T3a+T3b (n=14) Logrank P-value<0.01 0 2 4 6 8 10 12 14 No. at Risk T1a+T1b T3a+T3b 191 14 145 4 91 3 53 2 Time (year) 28 0 16 0 6 0 0 0 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability 0.0 0.2 0.4 0.6 0.8 1.0 Solitary Kidney No (n=189) Yes (n=18) Logrank P-value<0.01 0 2 4 6 8 10 12 14 No. at Risk No Yes 189 18 140 10 88 7 50 6 Time (year) 27 2 14 2 6 0 0 0 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Variable Hazard RaAo 95% CI P-value Solitary kidney (Yes vs. No) 2.62 1.01 6.81 0.05 PosiAve margins (Yes vs. No) 5.53 2.02 15.13 <0.01 Number of tumors (>2 vs. 1) 16.65 6.52 42.54 <0.01 R.E.N.A.L. score (High vs. Low) 5.53 1.52 20.21 0.01 pt stage (pt3 vs. pt1) 3.44 1.07 11.08 0.04 Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Time between par&al nephrectomy and local recurrence = 24 months (IQR 6-51) Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Salvage surgery Open par&al nephrectomy Open radical nephrectomy Laparoscopic radical nephrectomy Robo&c par&al nephrectomy Salvage radiofrequency abla&on Observa&on Systemic therapy Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson OR &me for salvage surgery = 135.5 minutes (IQR 110.25-241.75) Es&mated blood loss = 575cc (IQR 256.25-850) Pathologic stage at salvage surgery T1 = 13 (26.5%) T3a = 7 (14.3%) T3b = 3 (6.1%) Wood E,, Karam JA, Submiped
Local Recurrence ader ParAal Nephrectomy: MD Anderson Treatment -Laparoscopic radical Nx -pt3a (5.5cm) -ccrcc, Grade 3 -Nega&ve margins -NED 28 months postop
3- RECURRENCE AFTER RADICAL NEPHRECTOMY
Local Recurrence ader Radical Nephrectomy
Local Recurrence ader Radical Nephrectomy
Local Recurrence ader Radical Nephrectomy
Local Recurrence ader Radical Incidence of <5% Nephrectomy
Local Recurrence: USC 11 pa&ents 10 with no metastases at presenta&on Most pa&ents had symptoms Presented 31 months aper ini&al surgery 2 postopera&ve deaths 2 died of cancer at 8 and 22 months 3 died of causes unrelated to cancer recurrence 4 pa&ents were without disease at a follow-up of 35, 46, 48 and 211 months Esrig D. J Urol. 1992
Local Recurrence: MDACC 16 pa&ents with locally recurrent RCC 8 pa&ents received neoadjuvant Rx, 7 of these received addi&onal adjuvant Rx 7 IFNα based 1 IL-2 based Neoadjuvant group - 50% no evidence of cancer Surgery alone group - 25% no evidence of cancer Tanguay S. J Urol. 1996
Local Recurrence: MDACC 15 pa&ents had complete resec&on (of the 16) 12 had clear margins à 6 were free of cancer 12 of the 16 were alive at 2 years aper second surgery Tanguay S. J Urol. 1996
Local Recurrence: Mayo Clinic Itano NB. J Urol. 2000
Sandhu S. BJU Int. 2005 Local Recurrence: Royal Marsden 16 pa&ents (9 year period) 2 - unresectable 2 - residual adrenal recurrence 6 - retroperitoneal LN s 6 - renal bed 1 liver; 1 stomach; 1 spleen 2 - diaphragm 8 pa&ents given neoadjuvant Rx Of 14 resected, 6 Margin + Margin status predicted local and distant DFS (p < 0.05) Median f/u - 1 year Median &me to relapse - 2.4 months Median &me to metastasis - 4.3 months 5 pa&ents remain disease free
Local Recurrence: MD Anderson 1990-2014 Experience 102 pa&ents had surgery for local recurrence 84.3% of the pa&ents à radical nephrectomy at outside ins&tu&ons à subsequently referred to MDACC for local recurrence surgery Thomas AZ,, Karam JA. J Urol. 2015
Local Recurrence: MD Anderson Experience Time from nephrectomy to local recurrence diagnosis was 1.5 years At &me of nephrectomy Median age 55 years 79.4% had open surgery 60.8% were pt3-4 (invading renal vein/vena cava, fat or other organs) 19.6% were pn1 (posi&ve lymph nodes) 13.7% had posi&ve margins Thomas AZ,, Karam JA. J Urol. 2015
Local Recurrence: MD Anderson Experience Area of local recurrence 48% - SoP &ssue/renal fossa 40.2% - Lymph nodes 11.8% - Adrenal gland At &me of local recurrence surgery 41.2% had symptoms 45.1% received neoadjuvant Rx Thomas AZ,, Karam JA. J Urol. 2015
Local Recurrence: MD Anderson Experience Median local recurrence size = 4.5cm Open surgery for 97.1% of pa&ents Major complica&ons = 14.7% Blood loss = 700 ml Median surgery dura&on = 3.5 hours Median hospital stay = 1 week Thomas AZ,, Karam JA. J Urol. 2015
Local Recurrence: MD Anderson Experience 58.8% of pa&ents had cancer relapse aper local recurrence surgery Median &me to second relapse ~ 2 years Median survival aper second relapse ~5.5 years Predictors of worse outcomes aper surgery for local recurrence Posi&ve lymph nodes at &me of ini&al nephrectomy Larger size of local recurrence Thomas AZ,, Karam JA. J Urol. 2015
CSS-by Site of Recurrence Cancer Specific Survival Median CSS (months) ± SE SoP &ssue 93 ± 27 Lymph node 61 ± 12 Adrenal NA Lymph node Adrenal SoP &ssue Months Thomas AZ,, Karam JA. J Urol. 2015
Local Recurrence ader Radical Nephrectomy Treatment -Resec&on of all retroperitoneal masses -Resec&on of renal artery and vein stump -Distal pancreatectomy -Splenectomy -LeP hemicolectomy -LeP adrenalectomy -Omentectomy -Par&al diaphragm resec&on -RPLND à NED 17 months postop
Take Home Messages Local recurrences are rare but can occur aper ini&al treatment Important to follow-up with urologist aper ini&al treatment Best treated in referral medical centers Surgical resec&on in pa&ents with good performance status For recurrence aper abla&on or PN- excellent For recurrence aper radical Nx ~40% cure
Thank you! Jose A. Karam, MD, FACS JAKaram@MDAnderson.org