Management of Locally Reccurent Renal Cell Carcinoma. Jose A. Karam, MD, FACS Assistant Professor Department of Urology
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1 Management of Locally Reccurent Renal Cell Carcinoma Jose A. Karam, MD, FACS Assistant Professor Department of Urology
2 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
3 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)
4 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%
5 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
6 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
7 Possible Scenarios? Local recurrence only (Best case scenario) Local recurrence + distant recurrence (metastasis)
8 Observa&on Abla&on Surgery Systemic therapy Treatment OpAons?
9 AUA guidelines EAU guidelines NCCN guidelines Guidelines? No recommenda&ons!!!
10 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)
11 Outline Recurrence aper abla&on Recurrence aper par&al nephrectomy Recurrence aper radical nephrectomy
12 1- RECURRENCE AFTER ABLATION THERAPY
13 Local Recurrence ader AblaAon
14 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
15 Surgery For Local Recurrence ader AblaAon : NCI 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
16 Surgery For Local Recurrence ader AblaAon : CCF (Updated) 27 pa&ents ( ) 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
17 Surgery For Local Recurrence ader AblaAon: MD Anderson Experience 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
18 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
19 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
20 2- RECURRENCE AFTER PARTIAL NEPHRECTOMY
21 Local Recurrence ader ParAal Nephrectomy
22 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
23 Local Recurrence ader ParAal Nephrectomy: Mayo Clinic 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
24 Local Recurrence ader ParAal Nephrectomy: NCI 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
25 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
26 Local Recurrence ader ParAal Nephrectomy: MD Anderson 44 pa&ents with local recurrence aper PN 163 controls (no recurrence) Wood E,, Karam JA, Submiped
27 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
28 Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability Surgical Margin Negative (n=193) Positive (n=12) Logrank P-value< No. at Risk Negative Positive Time (year) Wood E,, Karam JA, Submiped
29 Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability Under 6 (n=56) 7-9 (n=118) (n=16) Logrank P-value< No. at Risk Under Time (year) Wood E,, Karam JA, Submiped
30 Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability (n=151) 2 (n=15) >2 (n=14) Logrank P-value< No. at Risk 1 2 > Time (year) Wood E,, Karam JA, Submiped
31 Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability T1a+T1b (n=191) T3a+T3b (n=14) Logrank P-value< No. at Risk T1a+T1b T3a+T3b Time (year) Wood E,, Karam JA, Submiped
32 Local Recurrence ader ParAal Nephrectomy: MD Anderson Recurrence Free Survival Probability Solitary Kidney No (n=189) Yes (n=18) Logrank P-value< No. at Risk No Yes Time (year) Wood E,, Karam JA, Submiped
33 Local Recurrence ader ParAal Nephrectomy: MD Anderson Variable Hazard RaAo 95% CI P-value Solitary kidney (Yes vs. No) PosiAve margins (Yes vs. No) <0.01 Number of tumors (>2 vs. 1) <0.01 R.E.N.A.L. score (High vs. Low) pt stage (pt3 vs. pt1) Wood E,, Karam JA, Submiped
34 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
35 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
36 Local Recurrence ader ParAal Nephrectomy: MD Anderson OR &me for salvage surgery = minutes (IQR ) Es&mated blood loss = 575cc (IQR ) Pathologic stage at salvage surgery T1 = 13 (26.5%) T3a = 7 (14.3%) T3b = 3 (6.1%) Wood E,, Karam JA, Submiped
37 Local Recurrence ader ParAal Nephrectomy: MD Anderson Treatment -Laparoscopic radical Nx -pt3a (5.5cm) -ccrcc, Grade 3 -Nega&ve margins -NED 28 months postop
38 3- RECURRENCE AFTER RADICAL NEPHRECTOMY
39 Local Recurrence ader Radical Nephrectomy
40 Local Recurrence ader Radical Nephrectomy
41 Local Recurrence ader Radical Nephrectomy
42 Local Recurrence ader Radical Incidence of <5% Nephrectomy
43 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
44 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
45 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
46 Local Recurrence: Mayo Clinic Itano NB. J Urol. 2000
47 Sandhu S. BJU Int 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 months Median &me to metastasis months 5 pa&ents remain disease free
48 Local Recurrence: MD Anderson 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
49 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
50 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
51 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
52 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
53 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
54 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
55 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
56 Thank you! Jose A. Karam, MD, FACS
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