Observation After Cytoreductive Nephrectomy in Patients With Synchronous Not Completely Resected Metastases of Renal Cell Carcinoma.

OBJECTIVE: To determine the time-to-targeted therapy (TTT) in patients with not completely resected low-volume oligometastatic disease who were observed following debulking cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). METHODS: Patients with synchronous mRCC with not completely resected low-volume metastases and in whom observation after CN was a multidisciplinary tumor board recommendation were identified from an approved institutional database. Patient data, International Metastatic Renal Cell Cancer Database Consortium (IMDC) risk, Fuhrman grade, site, and number of sites, time-to-progression (TTP), TTT, and overall survival (OS) were retrospectively analyzed. RESULTS: From 251 synchronous mRCC patients treated since 2006, 40 (15.9 %) were identified who underwent CN with observation as a result of low-volume multiple metastasis considered not completely resectable (19 single site and 21 with ≥2 sites). IMDC risk was favorable in 7, intermediate in 24, and poor in 9 patients. Median TTP was 6 (range 2-30) months and TTT was 16 (range 2-43) months. In 11 patients targeted therapy was further deferred by observation beyond Response Evaluation Criteria in Solid Tumors progression and in 10 patients by additional local therapy of the most rapidly progressing lesion. Median OS was 30 (range 2-71) months. CONCLUSION: In patients with synchronous mRCC and not completely resected low-volume metastasis, the TTT following CN was substantial. Local therapy to control the most rapidly progressing lesion or observation beyond progression was an additional means to defer systemic therapy.

Comparison of pre-treatment MSKCC and IMDC prognostic risk models in patients with synchronous metastatic renal cell carcinoma treated in the era of targeted therapy.

PURPOSE: To compare prognostic performance of MSKCC and IMDC risk models in patients with synchronous mRCC. METHODS: Retrospective analysis of pre-therapeutic MSKCC and IMDC prognostic factors and outcomes in patients with synchronous mRCC treated at a single institute in the targeted therapy era was performed. Cytoreductive nephrectomy (CN) was performed in patients with WHO performance 0-1 and limited metastasis. RESULTS: Of 190 patients, only 2 had favourable risk. Overall, 141 patients received targeted therapy and 97 underwent CN. By MSKCC score, 143 (76.1 %) patients were intermediate risk (median OS 16 months) but only 97 (51.9 %) by IMDC (median OS 23 months). Conversely, 46 of the MSKCC intermediate-risk patients (31.2 %) were IMDC poor risk. Only poor risk by MSKCC and ≥4 IMDC factors had similar poor outcome (median OS 5 months and OS 2 years of 4.1 % and 10.4 %, respectively). Following CN, baseline elevated platelets and neutrophils decreased to normal in 61.5 and 75 %, respectively. This suggests that the primary tumour may influence baseline counts resulting in more IMDC poor risk. In both models, CN status was associated with better OS. CONCLUSION: Patients with synchronous mRCC and poor risk by MSKCC or ≥4 IMDC factors have a short survival expectancy, and CN may not be the primary objective in this population. Conversely, with either MSKCC or IMDC intermediate risk the probability to survive 2 years is 38.6-45.7 %, which suggests that a subgroup of patients live long enough to derive a potential benefit of CN.

Baseline tumor volume in assessing prognosis of patients with intermediate-risk synchronous metastatic renal cell carcinoma.

OBJECTIVE: To analyze if prediction of survival for patients with synchronous metastatic renal cell cancer (mRCC) could be further refined by baseline volume of the primary tumor, the metastases, or the remaining volume after surgery; this study was performed because survival expectancies of patients with intermediate-risk mRCC vary substantially. MATERIAL AND METHODS: The predictive value of the different volumes on overall survival (OS) was analyzed retrospectively in patients with intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk profile and ≤3 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) factors, who received sunitinib in our institute. Tumor volumes were calculated on segmented computed tomography using in-house developed software. A multivariate analysis was performed including number of metastatic sites and baseline tumor burden (TB). RESULTS: A total of 68 patients were included. Median OS for patients without cytoreductive nephrectomy (CN) was 6 months (95% CI: 3.0-8.9mo) vs. 31 months (95% CI: 23.1-38.8mo) for those with CN, respectively. More second-line treatment was given after CN (49% vs. 17%, P = 0.125). There was no correlation between tumor volume and TB measured by Response Evaluation Criteria in Solid Tumors. Of all included clinical and volumetric parameters, remaining volume after CN, CN status and 2 vs. 3 IMDC factors were significantly correlated with OS. In the Cox regression analysis, CN was the only remaining significant parameter (P = 0.003). CONCLUSIONS: None of the baseline volumetric parameters is an independent prognostic factor in patients with intermediate MSKCC risk mRCC with≤3 IMDC factors receiving sunitinib. Only CN status correlated significantly with prognosis. None of the baseline volumes nor TB by Response Evaluation Criteria in Solid Tumors was associated with CN status, suggesting that extent of disease had no significant influence on the decision to perform surgery.

The role of cytoreductive surgery in the era of targeted agents.

PURPOSE OF REVIEW: Two randomized trials were initiated to define the role and sequence of cytoreductive nephrectomy in combination with VEGF-targeted therapy for metastatic renal cell cancer. While these trials will not report before the end of 2016, recent retrospective population-based studies published real-world data on incidence, treatment, prognosis and outcome that may help to better define the role of cytoreductive nephrectomy for this heterogeneous patient population in the targeted therapy era. RECENT FINDINGS: Since the introduction of targeted agents, utilization of cytoreductive nephrectomy has declined. Potentially more patients are being treated with their primary tumours in place. Some countries also observed an additional decline in the incidence of primary metastatic disease. Although large population-based studies consistently demonstrate a survival benefit after cytoreductive nephrectomy, confounding factors preclude definite conclusions. However, patients with a life expectancy of less than 1 year or at least four IMDS risk factors may not benefit from cytoreductive nephrectomy. SUMMARY: Recent retrospective data suggest a more refined use of cytoreductive nephrectomy in the targeted therapy era. With the exception of patients in whom cytoreductive nephrectomy and resection of solitary or oligometastasis may result in cure or delay of systemic therapy, performance, prognostic models and life expectancy estimates help to define the role of cytoreductive nephrectomy in the individual patient.