Effect of Obesity and Overweight Status on Complications and Survival After Minimally Invasive Kidney Surgery in Patients with Clinical T2-4 Renal Masses.

Objective: To evaluate the effect of obesity and overweight on surgical, functional, and survival outcomes in patients with large kidney masses after minimally invasive surgery. Materials and Methods: Within a multicenter multinational dataset, patients found to have ≥cT2 renal mass and treated with minimally invasive (laparoscopic or robotic) kidney surgery (radical or partial nephrectomy) during the period 2003 to 2017 were abstracted. They were stratified according to the body mass index classes as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Mixed models and Cox proportional hazard regression tested differences in complication rates, estimated glomerular filtration rate (eGFR) change over time, overall mortality (OM), and disease recurrence (DR) rates. Results: Of 812 patients, 30.6% were normal weight, 42.7% were overweight, and 26.7% obese. Overweight (odds ratio 0.82, 95% confidence interval [CI]: 0.51-1.31, p = 0.406) and obese patients (OR: 0.81, 95% CI: 0.44-1.47, p = 0.490) experienced similar complication rates than normal weight. Moreover, no statistically significant differences in eGFR were found for overweight (p = 0.129) or obese (p = 0.166) patients compared to normal weight. However, higher OM rates were recorded in overweight (hazard ratio [HR] 3.59, 95% CI: 1.03-12.51, p = 0.044), as well as in obese, patients (HR 7.83, 95% CI: 2.20-27.83, p = 0.002). Similarly, higher DR rates were recorded in obese (HR 2.76, 95% CI: 1.40-5.44, p = 0.003) patients. Conclusions: Obese and overweight patients do not experience higher complication rates or worse eGFR after minimally invasive kidney surgery, which therefore can be deemed feasible and safe also in this subset of patients. Nevertheless, obese and overweight patients seem to carry a higher risk of OM, and therefore, they should undergo a strict follow-up after surgery.

Robotic partial nephrectomy versus radical nephrectomy in elderly patients with large renal masses.

BACKGROUND: Recent evidence suggests that the "oldest old" patients might benefit of partial nephrectomy (PN), but decision-making for this subset of patients is still controversial. Aim of this study is to compare outcomes of robotic partial (RPN) or radical nephrectomy (RRN) for large renal masses in patients older than 65 years. METHODS: We identified 417≥65 years old patients who underwent RRN or RPN for cT1b or ≥cT2 renal mass at 17 high volume centers. Propensity score match analysis was performed adjusting for age, ASA≥3, pre-operative eGFR, and clinical tumor size. Predictors of complications, functional and oncological outcomes were evaluated in multivariable logistic and Cox regression models. RESULTS: After propensity score analysis, 73 patients in the RPN group were matched with 74 in the RRN group. R.E.N.A.L. Score (9.6±1.7 vs. 8.6±1.7; P<0.001), and high complexity (56 vs. 15%; P=0.001) were higher in the RRN. Estimated blood loss was higher in the RPN group (200 vs. 100 mL; P<0.001). RPN showed higher rate of overall complications (38 vs. 23%; P=0.05), but not major complications (P=0.678). At last follow-up, RPN group showed better functional outcomes both in eGFR (55.4±22.6 vs. 45.7±15.7 mL/min; P=0.016) and lower eGFR variation (9.7 vs. 23.0 mL/min; P<0.001). The procedure type was not associated with recurrence free survival (RFS) (HR: 0.47; P=0.152) and overall mortality (OM) (0.22; P=0.084). CONCLUSIONS: RPN in elderly patients with large renal masses provides acceptable surgical, and oncological outcomes allowing better functional preservation relative to RRN. The decision to undergo RPN in this subset of patients should be tailored on a case by case basis.

Robotic versus laparoscopic radical nephrectomy: a large multi-institutional analysis (ROSULA Collaborative Group).

OBJECTIVE: To compare the outcomes of robotic radical nephrectomy (RRN) to those of laparoscopic radical nephrectomy (LRN) for large renal masses. METHODS: This was a retrospective analysis of RRN and LRN cases performed for large (≥ cT2) renal masses from 2004 to 2017 and collected in the multi-institutional international database (ROSULA: RObotic SUrgery for LArge renal masses). Peri-operative, functional, and oncologic outcomes were compared between each approach. Descriptive analyses were performed and presented as medians with interquartile ranges. Inverse probability of treatment weighting-adjusted multivariable analyses were used to identify predictors of peri-operative complications. Kaplan-Meier analysis and Cox regression models were used to assess survival outcomes. RESULTS: A total of 941 patients (RRN = 404, LRN = 537) were identified. There was no difference in terms of gender, age, and clinical tumor size. Over the study period, RRN had an annual increase of 11.75% (95% CI [7.34, 17.01] p < 0.001) and LRN had an annual decline of 5.39% (95% CI [-6.94, -3.86] p < 0.001). Patients undergoing RRN had higher BMI (27.6 [IQR 24.8-31.1] vs. 26.5 [24.1-30.0] kg/m2, p < 0.01). Operative duration was longer for RRN (185.0 [150.0-237.2] vs. 126 [90.8-180.0] min, p < 0.001). Length of stay was shorter for RRN (3.0 [2.0-4.0] vs. 5.0 [4.0-7.0] days, p < 0.001). RRN cases presented more advanced disease (higher pathologic staging [pT3-4 52.5 vs. 24.2%, p < 0.001], histologic grade [high grade 49.3 vs. 30.4%, p < 0.001], and rate of nodal disease [pN1 5.4 vs. 1.9%, p < 0.01]). Surgical approach did not represent an independent risk factor for peri-operative complications (OR 1.81 95% CI [0.97-3.39], adjusted p = 0.2). The main study limitation is the retrospective design. CONCLUSIONS: This study represents the largest known multi-center comparison between RRN and LRN. The two procedures seem to offer similar peri-operative outcomes. Notably, RRN has been increasingly utilized, especially in the setting of more advanced and surgically challenging disease without increasing the risk of peri-operative complications.

STAT5A/B Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair.

Purpose: The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy.Experimental Design: Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in prostate cancer cells, xenograft tumors, and patient-derived prostate cancers ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing prostate cancer xenograft tumors.Results: Stat5a/b is critical for Rad51 expression in prostate cancer via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of Stat5a/b suppressed HR DNA repair while not affecting NHEJ DNA repair. Pharmacologic Stat5a/b inhibition potently sensitized prostate cancer cell lines and prostate cancer tumors to radiation, while not inducing radiation sensitivity in the neighboring tissues.Conclusions: This work introduces a novel concept of a pivotal role of Jak2-Stat5a/b signaling for Rad51 expression and HR DNA repair in prostate cancer. Inhibition of Jak2-Stat5a/b signaling sensitizes prostate cancer to radiation and, therefore, may provide an adjuvant therapy for radiation to reduce radiation-induced damage to the neighboring tissues. Clin Cancer Res; 24(8); 1917-31. ©2018 AACR.