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The probability of nodal and distant metastasis in patients (pts) with very-low, low, and favorable intermediate risk (FIR) prostate cancer (PCa) is considered low. Current NCCN and AUA/ASTRO guidelines do not recommend PSMA PET staging for these men. However, it has been reported that pts assigned to the FIR category are more likely than low-risk pts to have adverse pathological findings (upstaging and upgrading) at radical prostatectomy (RP) with a trend toward shorter recurrence-free survival. Early detection of clinically significant disease, extraprostatic extension, seminal vesicle invasion, N1 or M1 disease may change medical management in FIR pts and improve treatment outcomes. The purpose of this study is to explore whether piflufolastat F 18 PET/CT or PET/MR can detect higher risk disease in men previously assessed as FIR by standard of care methods. We hypothesize that piflufolastat F 18 PET will detect non-organ confined disease or upgrade pts to International Society of Urologic Pathologists (ISUP) grade ≥3 PCa in at least 5% of FIR subjects. This trial will also assess the ability for PET to better assess the volume and extent of the intraprostatic cancers. MIRROR is a phase 4, open label single arm multicenter study designed to evaluate the diagnostic performance and safety of piflufolastat F 18 in men with newly diagnosed FIR PCa. Eligible male pts must be ≥18 years of age, no prior PCa treatment, have a life expectancy of at least 13 months as determined by investigator, and confirmed FIR PCa per 2023 NCCN guidelines. The date of the prostate biopsy should be no sooner that 2 weeks and no later than 3 months prior to piflufolastat F 18 PSMA PET imaging. Participants will receive a single dose of piflufolastat F 18 injection followed by a single PET/CT or PET/MRI from mid-thigh through skull vertex acquired at 1 to 2 hours post-injection. Pts with a positive study scan results suspicious for PCa ISUP grade ≥3 or non-organ confined disease may be asked to undergo additional diagnostic test(s) for PCa and/or RP with pelvic lymph node dissection within 2 to 90 days after study scan to determine a truth standard. Pts will be monitored for up to 12 months to collect information about PCa treatment decisions and PSA results. The primary objective is to determine the detection rate defined as the proportion of participants with PCa in whom piflufolastat F 18 PET detected intraprostatic ISUP grade ≥3 lesions as confirmed by pathology, or in whom piflufolastat F 18 PET detected the presence of either/or extraprostatic extension, seminal vesicle invasion, regional lymph node involvement, distant metastases. Additional objectives include: change in intended patient clinical management, correct localization rate, true detection rate, sensitivity, specificity, PPV & NPV against reference standard. The study is currently open in the US. NCT06074510 TBD. TBD. [ABSTRACT FROM AUTHOR]

Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at three tertiary referral academic institutions between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors <7 cm, no or unilateral hydronephrosis, and no extensive carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) was similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p=0.07), distant failure-free (78 vs 82%, p=0.14), and pelvic nodal failure-free (96 vs 94%, p=0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p=0.02; 66 vs 78%, p<0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/282 (20.2%) TMT patients. This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative. [ABSTRACT FROM AUTHOR]