Renal fossa recurrence after nephrectomy for renal cell carcinoma: prognostic features and oncological outcomes.

OBJECTIVES: To describe the clinicopathological features associated with increased risk of renal fossa recurrence (RFR) after radical nephrectomy (RN) and to describe the prognostic features associated with cancer-specific survival (CSS) among patients with RFR treated with primary locally directed therapy, systemically directed therapy or expectant management. PATIENTS AND METHODS: The records of 2 502 patients treated with RN for unilateral, sporadic, localized renal cell carcinoma (RCC) between 1970 and 2006 were reviewed. CSS after RFR was estimated using the Kaplan-Meier method. Associations with the development of RFR and CSS after RFR were evaluated using Cox proportional hazards regression models. RESULTS: A total of 33 (1.3%) patients developed isolated RFR (iRFR) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases after RN (study cohort, N = 63). The median follow-up for the series was 9.0 years after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced pathological stage (pT2: hazard ratio [HR] 4.36, P = 0.004; pT3/4: HR 4.39, P = 0.003) and coagulative necrosis (HR 2.71, P = 0.006) were independently associated with increased risk of iRFR. The median time to recurrence was 1.5 years after RN among the 33 patients with iRFR, and 1.4 years among all patients. Overall, the median CSS was 2.5 years after diagnosis of iRFR, 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. After primary locally directed therapy (surgery, ablation or radiation), systemic therapy or expectant management, the 3-year CSS rates among patients with iRFR were 63%, 50% and 13% (P = 0.001) and were 64%, 50% and 28% (P = 0.006) among all patients, respectively. On multivariable analysis, when compared with observation, locally directed therapies were associated with a significantly decreased risk of death from RCC (HR 0.26, P < 0.001). CONCLUSIONS: Renal fossa recurrence is a rare event after RN for RCC and portends a poor prognosis, even in the absence of synchronous metastases. Development of iRFR is associated with advanced stage and aggressive tumour biology. Patients who underwent primary locally directed therapy had superior CSS compared with those treated with expectant management, supporting the use of aggressive local treatment in carefully selected patients with RFR. Future research is needed to determine the optimum role and sequencing of combined therapy in patients with this rare entity.

Decreased Skeletal Muscle Mass is Associated with an Increased Risk of Mortality after Radical Nephrectomy for Localized Renal Cell Cancer.

PURPOSE: We evaluate the association between severe skeletal muscle deficiency or sarcopenia, and disease progression, cancer specific mortality and all cause mortality in patients with localized renal cell carcinoma treated with radical nephrectomy. MATERIALS AND METHODS: The baseline lumbar skeletal muscle index of 387 patients treated with radical nephrectomy for nonmetastatic renal cell carcinoma between 2000 and 2010 was measured on preoperative computerized tomography. Sarcopenia was classified according to gender specific consensus definitions as male-skeletal muscle index less than 55 cm(2)/m(2) and female-skeletal muscle index less than 39 cm(2)/m(2). Progression-free, cancer specific and overall survival was estimated with the Kaplan-Meier method. Associations with progression, cancer specific mortality and all cause mortality were summarized with hazard ratios. RESULTS: Of 387 patients 180 (47%) had sarcopenia. Patients with sarcopenia were older, more likely to be male (77% vs 56%, p <0.001), to have a smoking history (67% vs 55%, p=0.02), and to have nuclear grade 3 or greater disease (67% vs 60%, p=0.05), but were otherwise similar to patients without sarcopenia. Median postoperative followup was 7.2 years. Patients with sarcopenia had inferior 5-year cancer specific survival (79% vs 85%, p=0.05) compared to those without sarcopenia, as well as significantly worse 5-year overall survival (65% vs 74%, p= 0.005). As a continuous variable, increasing skeletal muscle index was linearly associated with a decreased risk of cancer specific mortality and all cause mortality. Moreover, on multivariable analysis sarcopenia was associated with increased cancer specific mortality (HR 1.70, p=0.047) and all cause mortality (HR 1.48, p=0.039). CONCLUSIONS: Sarcopenia is independently associated with cancer specific mortality and all cause mortality after radical nephrectomy for renal cell carcinoma. These findings underscore the importance of assessing skeletal muscle index for risk stratification, patient counseling and treatment planning.

Standardizing the Definition of Biochemical Recurrence after Radical Prostatectomy-What Prostate Specific Antigen Cut Point Best Predicts a Durable Increase and Subsequent Systemic Progression?

PURPOSE: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression. MATERIALS AND METHODS: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test. RESULTS: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92). CONCLUSIONS: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy.

Complications and Outcomes Associated With Surgical Management of Renal Cell Carcinoma Involving the Liver: A Matched Cohort Study.

OBJECTIVE: To assess the safety and utility of more aggressive surgical resection of renal cell carcinoma involving the liver at the time of nephrectomy. MATERIALS AND METHODS: We identified 34 cases at our institution where patients underwent simultaneous nephrectomy and hepatic resection for direct hepatic invasion (n = 17) or metastatic renal cell carcinoma (n = 21). Perioperative outcomes and complication rates were compared with a matched referent cohort (n = 68) undergoing simultaneous nephrectomy and resection of non-hepatic locally invasive or metastatic disease. RESULTS: Of the 34 cases, 17 (50%) patients underwent hepatic resection for pT4 liver involvement and 21 (62%) patients underwent simultaneous nephrectomy and hepatic metastasectomy. Deep vein thrombosis occurred more frequently following hepatic resection (15% vs 1%, P = .02); however, no significant differences were noted in Clavien grade 3-4 complications (12% vs 3%, P = .10) or perioperative mortality (3% vs 0%, P = .67). Two-year cancer-specific and overall survival for patients undergoing hepatic resection and non-hepatic resection were 40% and 29% (hazard ratio: 0.72, P = .2) and 40% and 28% (hazard ratio: 0.80, P = .30), respectively. CONCLUSION: In carefully selected patients, hepatic resection at the time of nephrectomy is associated with a higher risk of deep vein thrombosis and may be associated with a trend toward an increased risk of short-term Clavien IV complications; however, perioperative and overall mortality are comparable with those in matched patients undergoing surgical resection of locally advanced or metastatic disease involving non-hepatic organs.

Oncologic surveillance in bladder cancer following radical cystectomy: A systematic review and meta-analysis.

PURPOSE: The existing guidance on bladder cancer surveillance following radical cystectomy is limited and variable. Additionally, the effect of surveillance on mortality is debatable. Herein, we perform a systematic review to evaluate the characteristics of alternative oncologic surveillance protocols and determine the association of detection of asymptomatic vs. symptomatic recurrences on mortality. METHODS: An electronic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases was performed from 1970 to 2015. In all, 3 reviewers independently assessed the 1,729 candidate studies for eligibility and abstracted data based on an a priori established protocol. Outcomes were pooled using random effects meta-analysis. RESULTS: We identified 7 studies for inclusion that were uncontrolled and thereby represented a body of evidence at high risk of bias; 5 studies developed surveillance protocols using a methodology similar to that of established guidelines. The majority proposed a pathologic stage-stratified approach, but ended surveillance for all patients at 5 years. Detection of asymptomatic recurrences was associated with a nonsignificant reduction in mortality (relative risk = 0.78; 95% CI: 0.58-1.04). This effect became statistically significant when upper and lower urinary tract recurrences were included in the analyses (relative risk = 0.69; 95% CI: 0.59-0.79). CONCLUSIONS: Only sparse evidence supports alternative oncologic surveillance protocols for bladder cancer following radical cystectomy. The majority of existing protocols proposed similar strategies to those recommended by published guidelines. Detecting asymptomatic recurrences may lead to a reduction in overall mortality, which could provide a rationale for surveillance.

Concordance of Pathologic Features Between Metastatic Sites and the Primary Tumor in Surgically Resected Metastatic Renal Cell Carcinoma.

OBJECTIVE: To evaluate the concordance of pathologic features in metastatic renal cell carcinoma (RCC) between the primary nephrectomy and metastasectomy specimens. METHODS: Primary nephrectomy (n = 454) and matched metastasectomy specimens (n = 680) from patients treated between 1970 and 2009 for RCC were re-reviewed by 1 urologic pathologist in a blinded fashion. RCC histologic subtype, grade, coagulative necrosis, and the presence of sarcomatoid differentiation were compared between the primary and the metastatic tumor with kappa statistics. RESULTS: Concordance with the primary tumor was observed for subtype in 647 (95%, kappa = 0.71) of the metastases, for grade in 411 (60%, kappa = 0.35), necrosis in 460 (68%, kappa = 0.32), and sarcomatoid differentiation in 643 (95%, kappa = 0.60). Upgrading was observed in 100%, 63%, and 13% of patients with grades 1, 2, and 3 primary tumors, respectively (no patient had a grade 1 metastatic lesion). Metastatic tumors treated with metastasectomy within 30 days of nephrectomy (n = 145) had similar rates of concordant subtype, necrosis, and sarcomatoid differentiation to those undergoing metastasectomy beyond 30 days from nephrectomy (P >.05 for all), but had higher rates of concordant grade (71% vs 58%, P = .003). Pre-metastasectomy exposure to systemic targeted or immunotherapy was not associated with a change in concordance of histopathologic features. CONCLUSION: Among 454 surgically managed metastatic RCC patients, we observed a high degree of concordance for histologic subtype and sarcomatoid differentiation, and varying degrees of discordance for grade and coagulative tumor necrosis, between primary and metastatic tumors. Further investigation is warranted to understand the biologic and therapeutic implications of these observations.

Evaluation of current surveillance guidelines following radical cystectomy and proposal of a novel risk-based approach.

BACKGROUND: Evidence supporting surveillance guidelines after radical cystectomy (RC) are lacking. Herein, we evaluate the ability of the National Comprehensive Cancer Network (NCCN) guidelines and the European Association of Urology (EAU) guidelines to capture recurrences and provide an alternative approach that balances risks of recurrence with non-bladder cancer death. METHODS: We identified 1,797 patients who had M0 urothelial carcinoma who underwent RC at our institution between 1980 and 2007. The success of current guidelines to capture recurrences was assessed by calculating the percentage of recurrences detected during the recommended follow-up time: the NCCN--2 years and the EAU--5 years. An alternative protocol was created using Weibull distributions, which estimate when a patient׳s risk of non-bladder cancer death exceeds their risk of recurrence. RESULTS: At a median follow-up of 10.6 years (interquartile range : 6.8-15.2), a total of 714 patients recurred. Of these, 491 (68.7%) would have been detected by the NCCN guidelines and 642 (89.8%) by the EAU guidelines. Using a risk-adapted approach, vastly different surveillance durations were appreciated. For example, for patients older than 80 years with pT0Nx-0 or pTa/CIS/1Nx-0 disease, recurrence risk to any location never exceeded their risk of non-bladder cancer death, whereas for patients aged 60 years and younger with pT3/4Nx-0 or pTanyN+disease, risk of abdominal/pelvis recurrence remained greater than their risk of non-bladder cancer death for>20 years. CONCLUSIONS: The duration of post-RC follow-up recommended by the NCCN and the EAU does not comprehensively capture recurrences. A surveillance algorithm based on the interaction between recurrence risk and competing health factors individualizes recommendations and may improve capture of recurrences and resource allocation.

Oncologic Surveillance After Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach.

PURPOSE: The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death. PATIENTS AND METHODS: We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (< 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence. RESULTS: At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age. CONCLUSION: We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation.