Thompson, R. Houston

Objective To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node ( RPLN ) recurrence of renal cell carcinoma ( RCC ) using a multicentre international cohort. Patients and Methods In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pT any N any M0 disease. Progression‐free ( PFS ) and cancer‐specific survival ( CSS ) were estimated using the Kaplan–Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. Results The median (interquartile range, IQR ) age at resection was 57.0 (50.0–62.5) years. The median ( IQR ) time to RPLN recurrence after nephrectomy was 12.6 (6.9–39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5–24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7–44.2] months) ( P = 0.66). The median ( IQR ) size of the RPLN recurrence before resection was 2.6 (1.9–5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median ( IQR ) follow‐up after RPLN resection for patients alive at last follow‐up was 28.0 (13.7–51.2) months. During follow‐up, 26 patients developed RCC recurrence, at a median ( IQR ) of 9.9 (4.0–18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3‐ and 5‐year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). Conclusion Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.

Objective To evaluate how many patients could have undergone partial nephrectomy ( PN ) rather than radical nephrectomy ( RN ) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter‐observer agreement. Patients and Methods Pre‐ and post‐systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated. Results The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment ( P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate‐complexity κ was 0.611 vs a high‐complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8‐times higher after treatment with axitinib. Conclusions There is considerable variability in inter‐observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori .

ObjectivesTo evaluate the differences in estimated glomerular filtration rate decline by urinary diversion type (incontinent diversion vs continent diversion) and preoperative estimated glomerular filtration rate among patients undergoing radical cystectomy and urinary diversion.MethodsWe evaluated 1383 patients treated with radical cystectomy between 1980–2006 who had a preoperative estimated glomerular filtration rate of 45‐89 mL/min/1.73 m2. Estimated glomerular filtration rate was estimated using Chronic Kidney Disease Epidemiology Collaboration equations, and patients were stratified by preoperative estimated glomerular filtration rate into chronic kidney disease 2 (estimated glomerular filtration rate 60–89 mL/min/1.73 m2) and chronic kidney disease 3a (estimated glomerular filtration rate 45–59 mL/min/1.73 m2). Multiple definitions of estimated glomerular filtration rate decline were evaluated: (i) 10‐point decline in estimated glomerular filtration rate; (ii) 20% decline in estimated glomerular filtration rate; and (iii) 10% decline in estimated glomerular filtration rate. Time to estimated glomerular filtration rate decline was compared using the Kaplan–Meier method stratified by diversion type. Cox regression models were used to evaluate the association of diversion type with estimated glomerular filtration rate decline risk.ResultsIn total, 74% (1021/1383) of patients underwent incontinent diversion and 26% (362/1383) underwent continent diversion. Preoperative chronic kidney disease 2 and chronic kidney disease 3a were noted among 59% and 41% of patients who underwent incontinent diversion, versus 74% and 26% with continent diversion. Median follow up after RC was 11.2 years. The rate of estimated glomerular filtration rate decline in patients with incontinent diversion versus continent diversion was similar when stratified by preoperative chronic kidney disease 2 and preoperative chronic kidney disease 3a, regardless of estimated glomerular filtration rate decline definition. On multivariable analysis, continent diversion was not associated with estimated glomerular filtration rate decline for patients with preoperative chronic kidney disease 3a.ConclusionsThe risk of estimated glomerular filtration rate decline over 10 years was not significantly different after incontinent diversion versus continent diversion among patients with preoperative chronic kidney disease 2 or chronic kidney disease 3a. Continent diversion does not appear to confer an independently increased risk of estimated glomerular filtration rate decline in patients with preoperative chronic kidney disease 3a.

ObjectiveTo review our experience with radical cystectomy for small cell carcinoma of the bladder, to compare outcomes with a cohort of patients with urothelial carcinoma, and to determine the effect of adjuvant chemotherapy and pathology re‐review in this setting.MethodsAmong 2427 patients who underwent radical cystectomy, 68 patients had small cell carcinoma of the bladder. Patients with small cell carcinoma of the bladder were compared with an unmatched cohort of 1146 patients with urothelial carcinoma, and were then matched (1:2) based on TNM stage. Survival was estimated using the Kaplan–Meier method, and Cox models were used to evaluate association of clinicopathological features with outcome.ResultsAmong the 68 small cell carcinoma of the bladder patients, 37 (54%) were found to have small cell carcinoma of the bladder only after pathology re‐review. Patients with small cell carcinoma of the bladder had a higher rate of advanced (pT3/4) tumor stage (84% vs 46%; P < 0.0001) and pN+ disease (37% vs 20%; P = 0.001) compared with patients with urothelial carcinoma. When matched for stage and lymph node status, no significant difference in 5‐year cancer‐specific survival was observed between the two groups (27% vs 29%; P = 0.64). Among small cell carcinoma of the bladder patients, those receiving adjuvant chemotherapy had improved 5‐year overall survival compared with patients who did not receive adjuvant chemotherapy (43% vs 20%; P = 0.03), and a trend toward superior cancer‐specific survival (40% vs 23%; P = 0.07).ConclusionsSmall cell carcinoma of the bladder is often an unrecognized pathological entity, which is associated with a higher rate of locally advanced and N+ disease. However, although when matched for pathological features, survival outcomes appear similar to urothelial carcinoma. Small cell carcinoma of the bladder patients receiving adjuvant chemotherapy had improved overall survival and cancer‐specific survival, and these results require further investigation.

Objective To evaluate the clinical and radiographic predictors of the need for partial or circumferential resection of the inferior vena cava ( IVC ) requiring complex vascular reconstruction during venous tumour thrombectomy for renal cell carcinoma ( RCC ). Patients and Methods Data were collected on 172 patients with RCC and IVC (levels I– IV ) venous tumour thrombus who underwent radical nephrectomy with tumour thrombectomy at the Mayo Clinic between 2000 and 2010. Preoperative imaging was re‐reviewed by one of two radiologists blinded to details of the patient's surgical procedure. Univariable and multivariable associations of clinical and radiographic features with IVC resection were evaluated by logistic regression. A secondary analysis was used to assess the ability of the model to predict histological invasion of the IVC by the tumour thrombus. Results Of the 172 patients, 38 (22%) underwent IVC resection procedures during nephrectomy. Optimum radiographic thresholds were determined to predict the need for IVC resection based on preoperative imaging included a renal vein diameter at the renal vein ostium ( RV o) of 15.5 mm, maximum anterior–posterior ( AP ) diameter of the IVC of 34.0 mm and AP and coronal diameters of the IVC at the RV o of 24 and 19 mm, respectively. On multivariable analysis, the presence of a right‐sided tumour (odds ratio 3.3; P = 0.017), an AP diameter of the IVC at the RV o of ≥24.0 mm (odds ratio 4.4; P = 0.017), and radiographic identification of complete occlusion of the IVC at the RV o (odds ratio 4.9; P < 0.001) were associated with a significantly increased risk of IVC resection. The c‐index for the model was 0.81. Conclusions We present a multivariable model of the radiographic features associated with the need for IVC resection during tumour thrombectomy. Pending external validation, this model may be used for preoperative planning, patient counselling and planned involvement of vascular surgical colleagues in anticipation of the need for complex vascular repair.

Purpose The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide guidelines for surveillance after surgery for renal cell carcinoma (RCC). Herein, we assess the ability of the guidelines to capture RCC recurrences and determine the duration of surveillance required to capture 90%, 95%, and 100% of recurrences. Patients and Methods We evaluated 3,651 patients who underwent surgery for M0 RCC between 1970 and 2008. Patients were stratified as AUA low risk (pT1Nx-0) after partial (LR-partial) or radical nephrectomy (LR-radical) or as moderate/high risk (M/HR; pT2-4Nx-0/pTanyN1). Guidelines were assessed by calculating the percentage of recurrences detected when following the 2013 and 2014 NCCN and AUA recommendations, and associated Medicare costs were compared. Results At a median follow-up of 9.0 years (interquartile range, 5.7 to 14.4 years), a total of 1,088 patients (29.8%) experienced a recurrence. Of these, 390 recurrences (35.9%) were detected using 2013 NCCN recommendations, 742 recurrences (68.2%) were detected using 2014 NCCN recommendations, and 728 recurrences (66.9%) were detected using AUA recommendations. All protocols missed the greatest amount of recurrences in the abdomen and among pT1Nx-0 patients. To capture 95% of recurrences, surveillance was required for 15 years for LR-partial, 21 years for LR-radical, and 14 years for M/HR patients. Medicare surveillance costs for one LR-partial patient were $1,228.79 using 2013 NCCN, $2,131.52 using 2014 NCCN, and $1,738.31 using AUA guidelines. However, if 95% of LR-partial recurrences were captured, costs would total $9,856.82. Conclusion If strictly followed, the 2014 NCCN and AUA guidelines will miss approximately one third of RCC recurrences. Improved surveillance algorithms, which balance patient benefits and health care costs, are needed.