Alon Lazarovich

Introduction: Current guidelines endorse the use of perioperative chemotherapy (POC) in muscle-invasive bladder cancer (MIBC) to enhance the long-term overall survival (OS) compared to radical cystectomy (RC) alone. This study aims to assess the impact of POC on the OS in frail and morbid (F-M) patients undergoing RC. Methods: A retrospective multicenter study of 291 patients who underwent RC between 2015 and 2019 was performed. Patients with both a Charlson comorbidity index ≥ 4 and Modified Frailty Index ≥ 2 were classified as the F-M cohort. We compared the clinical and pathological characteristics and outcomes of the F-M patients who received POC to those who underwent RC alone. Univariable and multivariable analyses were performed to identify the predictors of the OS. Results: The F-M cohort included 102 patients. POC was administered to 44% of these patients: neoadjuvant (NAC) to 31%, adjuvant (AC) to 19%, and both to 6 (6%). The OS was significantly lower in the F-M cohort compared to in the healthier patients (median OS 42 months, p = 0.02). The F-M patients who received POC were younger, less morbid and had better renal function. Although POC was marginally associated with improved OS in the univariable analysis (p = 0.06), this was not significant in the multivariable analysis (p = 0.50). NAC was associated with improved OS in the univariable analysis (p = 0.004) but not after adjustment for competing factors (p = 1.00). AC was not associated with the OS. Conclusions: POC does not improve the OS in F-M patients undergoing RC. Personalized treatment strategies and further prospective studies are needed to optimize care in this unique vulnerable population.

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Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with “negative” prostate ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with “negative” pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an “intense” prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a “negative” uptake (in the study group), and 45 (46%) had a “positive” uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.