Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma with Synchronous and Metachronous Nodal Disease.

INTRODUCTION: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND). METHODS: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. Histology was grouped as papillary, chromophobe, unclassified, and rare subtypes. Retrospective evaluation identified 2.5% (n = 40) of patients with nodal disease at time of nephrectomy (synchronous-ND) and 1.1% (n = 18) with metachronous nodal disease limited to the retroperitoneum (metachronous-ND). Patients' demographics and tumor characteristics were recorded and evaluated by univariate and multivariate cox regression models. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Patients who underwent tumor DNA sequencing during their clinical course were considered for genomic analysis. RESULTS: OS trended toward longer in metachronous-ND (51 vs 105 months; P = .2), though 23% of patients with synchronous-ND were recurrence-free at 45 months median follow-up. In multivariate analysis, rare histologies were associated with decreased OS (P = .030) and metachronous-ND with improved OS (P = .036). RFS and OS after S-LND was 15 and 96 months, respectively. Late onset of metachronous-ND/recurrence was associated with improved OS (P = .008). Genetic alterations in SETD2, TP53, B2M, and FGFR3 were exclusively seen in synchronous-ND, and tumor mutation burden (TMB) was also higher in patients with synchronous-ND (P = .016). CONCLUSIONS: Patients with metachronous-ND tend to have prolonged OS compared to synchronous-ND, but a substantial portion of patients with synchronous-ND still enter a durable disease-free state following LND. S-LND can likewise provide long-term survival, particularly in patients with longer time to metachronous nodal recurrence. Synchronous-ND was associated with SETD2, TP53, and NF2 alteration as well as higher TMB.

Benign splenic lesions in BAP1-tumor predisposition syndrome: a case series.

BAP1-Tumor Predisposition Syndrome (TPDS) is caused by germline variants in BAP1 and predisposes to solid tumors. After observation of a radiologically malignant-appearing splenic mass with benign pathology in a patient with BAP1-TPDS, we sought to retrospectively characterize splenic lesions in individuals with BAP1-TPDS seen at a comprehensive cancer center. A dedicated radiology review for splenic abnormalities was performed. We identified 37 individuals with BAP1-TPDS, 81% with a history of cancer. Of 33 individuals with abdominal imaging, 10 (30%) had splenic lesions, and none were shown to be malignant on follow-up. Splenectomy in an individual with suspected splenic angiosarcoma showed a benign vascular neoplasm with loss of nuclear staining for BAP1 in a subset of cells. Benign splenic lesions appear to be common and potentially BAP1-driven in individuals with BAP1-TPDS; confirmation of these findings could lead to more conservative management and avoidance of splenectomy.

Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

INTRODUCTION: Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database. METHODS: The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis. RESULTS: A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC. CONCLUSIONS: In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.

Microwave ablation of cT1a renal cell carcinoma: oncologic and functional outcomes at a single center.

PURPOSE: Percutaneous ablation is an established alternative to surgical intervention for small renal masses. Radiofrequency and cryoablation have been studied extensively in the literature. To date, series assessing the efficacy and safety of microwave ablation (MWA) are limited. We present a cohort of 110 renal tumors treated with MWA. METHODS: A review of the medical record between January 2015 and July 2019 was performed, retrospectively identifying 101 patients (110 tumors). All ablations were performed by a single board-certified urologist/interventional radiologist. Demographic information, intraoperative, postoperative, and follow-up surveillance data were recorded. RESULTS: Median (IQR) age was 69.7 years (60.8-77.0); 27 (24%) were female. Median (IQR) BMI was 27.0 (25.1-30.2) and Charleston Comorbidity Index was 5.0 (4.0-6.0). 82 tumors were biopsy-confirmed renal cell carcinoma/oncocytic neoplasms. Median (IQR) tumor size was 2.0 cm (1.5-2.6). Median (IQR) RENAL nephrometry score was 6.0 (5.0-8.0). Technical success was achieved in all patients and all but one patient were discharged on the same day. Median (IQR) eGFR at baseline and 1 year were 71.9 mL/min/1.73 m2 (56.5-82) and 63.0 mL/min/1.73 m2 (54.0-78.2); the difference was -5.3 (p = 0.12). Two Clavien-Dindo type-I complications, one type-II complication, and one type-III complication were experienced in this cohort. Median radiographic follow-up was 376.5 days with 2 tumors (2.4% of RCC/oncocytic neoplasms) having recurred to date. CONCLUSIONS: MWA is a safe and efficacious treatment option for small renal masses with minimal adverse events and low rates of recurrence in this cohort of 101 patients. Continued follow-up is needed to assess long-term outcomes.