Abstract:In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC.

Purpose Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We investigated the outcomes of patients with localized RPR treated with surgical resection. Methods This was a retrospective single-institutional study of 102 patients with RPR treated with surgery from 1990-2014. Demographics, clinical and pathological features, location of RPR, perioperative complications were reported using descriptive statistics. Recurrence free survival (RFS) and cancer-specific survival (CSS) were studied using univariate and multivariate analyses. Results Median age at RPR diagnosis was 55 years (IQR 49-64). Sixty-two (60.8%) patients were pT3-4 and 20 (19.6%) were pN1. No patients had distant metastatic disease at time of RPR surgery. Median time from nephrectomy to RPR diagnosis was 19 months (IQR 5-38.8). The median size of resected RPR was 4.5cm (IQR 2.7-7). Median follow up after RPR surgery was 32 months (IQR 16-57). Metastatic progression was observed in 60 (58.8%) patients after RPR surgery. Neoadjuvant and salvage systemic therapy were administered in 46 (45.1%) and 48 (47.1%) patients, respectively. On multivariate analysis, pathological nodal stage at original nephrectomy and maximum diameter of RPR were identified as independent risk factors for cancer specific death. Conclusion Clinico-pathological factors at the time of nephrectomy as well as RPR surgery are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR with acceptable complications, and still plays a dominant role in the management of isolated locally recurrent RCC.

Poor overall survival following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma with tumor thrombus is associated with inferior vena cava thrombus above the diaphragm, poor risk group, systemic symptoms or sarcomatoid dedifferentiation. Patients with expected poor overall survival should be considered for preoperative systemic therapy clinical trials.

Objectives To determine the extent of variability in the definitions of the ‘trifecta’ after radical prostatectomy (undetectable PSA, urinary continence and potency) to be found in the literature. To establish a consensus definition of the trifecta in an effort to standardize criteria and reporting. Materials and Methods A systematic review of published articles found in the PubMed database for the period from January 2003 to March 2012 was performed. The search queries included the keywords ‘radical prostatectomy,’ ‘prostatectomy outcome,’ and ‘trifecta’. Results A total of 86 publications were identified of which 14 were used for analysis. Eight different definitions of biochemical recurrence were reported, the most common definition being PSA ≥0.2 ng/mL. The definition of potency was the most variable. Ten different definitions of potency were found, with the most common being ‘having erections sufficient for intercourse with or without a phosphodiesterase‐5 inhibitor’. Nine different definitions of continence were found. The most common definition of continence was ‘wearing no pads’. Only six of the 14 articles used validated questionnaires in their outcome measures. Conclusions The definitions of trifecta reported in the literature are highly variable. We propose the following consensus definition based on our analysis: (1) PSA >0.2 ng/mL with confirmatory value; (2) attainment of erections sufficient for intercourse with or without oral pharmacological agents; (3) wearing zero pads. This consensus definition should be considered when designing studies and reporting outcomes of radical prostatectomy.

OBJECTIVE Renal cell carcinoma with sarcomatoid dedifferentiation(sRCC) is associated with higher stage of presentation and worse survival. The objective of this study was to examine the clinicopathological characteristics associated with overall survival(OS), specifically examining the percentage of sarcomatoid component(PSC). METHODS We reviewed clinicopathologic data for all nephrectomized patients with confirmed sRCC. Histologic slides were re-reviewed by dedicated GU pathologists to ascertain PSC. Patient characteristics were tabulated overall and by disease stage. Cutpoints in the PSC providing a meaningful difference in OS were identified by recursive partitioning analysis(RPA). Factors selected included age group, gender, race, clinical stage, tumor histology, presurgical systemic therapy, lymphovascular invasion, and tumor size. Kaplan-Meier method and log-rank test were used to assess differences in OS. RESULTS Among 186 patients with sRCC, 64(34%) had localized, and 122(66%) had metastatic disease at presentation. Patients had primarily clear cell histology(73%). Median follow-up was 12.1 months(range 0.1–242.2 months). Median OS was 12.6 months (95%CI 10.7–14.9 months). Univariate RPA identified a PSC cutpoint of 10% as prognostically significant. Patients with PSC>10% were at higher risk of death compared to patients with ≤10%(45% vs. 61% 1-year OS;P=0.04). Multivariate RPA revealed that tumor size, presence of metastatic disease, and PSC were significantly associated with OS. Among 4 identified groups, patients with localized disease and tumor size ≤10cm were most likely to be alive at 1 year(89%), and patients with metastatic disease and PSC>40% were least likely to be alive at 1 year(28%;p<0.001). CONCLUSION PSC appears to be a prognostic factor in patients with sRCC, with larger percentage of involvement portending a worse survival, especially in patients with metastatic disease.