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Rationale and Objectives: To evaluate whether a computed tomography (CT)-based computerized decision-support system for muscle-invasive bladder cancer treatment response assessment (CDSS-T) can improve identification of patients who have responded completely to neoadjuvant chemotherapy.Materials and Methods: Following Institutional Review Board approval, pre-chemotherapy and post-chemotherapy CT scans of 123 subjects with 157 muscle-invasive bladder cancer foci were collected retrospectively. CT data were analyzed with a CDSS-T that uses a combination of deep-learning convolutional neural network and radiomic features to distinguish muscle-invasive bladder cancers that have fully responded to neoadjuvant treatment from those that have not. Leave-one-case-out cross-validation was used to minimize overfitting. Five attending abdominal radiologists, four diagnostic radiology residents, two attending oncologists, and one attending urologist estimated the likelihood of pathologic T0 disease (complete response) by viewing paired pre/post-treatment CT scans placed side-by-side on an internally-developed graphical user interface. The observers provided an estimate without use of CDSS-T and then were permitted to revise their estimate after a CDSS-T-derived likelihood score was displayed. Observer estimates were analyzed with multi-reader, multi-case receiver operating characteristic methodology. The area under the curve (AUC) and the statistical significance of the difference were estimated.Results: The mean AUCs for assessment of pathologic T0 disease were 0.80 for CDSS-T alone, 0.74 for physicians not using CDSS-T, and 0.77 for physicians using CDSS-T. The increase in the physicians' performance was statistically significant (P < .05).Conclusion: CDSS-T improves physician performance for identifying complete response of muscle-invasive bladder cancer to neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Sacituzumab govitecan (SG) is a Trop-2-directed antibody–drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups. • With longer follow-up, response rate remains high (28%) in patients with advanced UC treated with sacituzumab govitecan. • Safety profile of sacituzumab govitecan was tolerable with low treatment discontinuation rates (7%). • Although incidence and grade of AEs varied across subgroups, AEs were managed similarly regardless of the UGT1A1 status. • UGT1A1 testing before SG initiation is not currently recommended in advanced UC as patients are closely monitored for AEs. • Other cohorts of the TROPHY-U-01 and TROPiCS-04 trials will continue to inform the impact of UGT1A1 status on safety. [ABSTRACT FROM AUTHOR]

Utilization of molecular imaging in men with recurrent prostate cancer after definitive treatment is rapidly increasing. However, randomized data to guide preferred treatment approaches after molecular imaging are lacking, particularly for men with radiorecurrent, localized-only disease. We sought to evaluate patterns of care in these men, in order to understand the referral patterns and care plans implemented as a result of molecular imaging. From 2018-2020, 822 men were enrolled at a single institution on a prospective study (NCT03396874) assessing the diagnostic performance of 68Ga-PSMA-11 PET (PSMA) in men with biochemical recurrence after initial definitive therapy. Among the 196 (24%) treated with upfront definitive radiation therapy (RT), 58 had an isolated local recurrence and form the cohort for the present analysis. We evaluated the patterns of care including specialty of ordering provider, patterns of consulted specialties after PSMA, and subsequent management. Fifty-eight men had PSMA positive radiorecurrent localized-only disease (n=58/196, 30%). PSMA for these men was most ordered by medical oncology (38%), urology (36%), and radiation oncology (24%). Median PSA at time of PSMA was 4.6 ng/mL. Median interval between initial RT and PSMA was 9 years. After PSMA, 101 consultations were completed, 40 urology (40%), 33 radiation oncology (32%), and 28 medical oncology (28%). Twenty-one percent of men saw all three specialties (n=12), 38% two (n=22), and 41% one (n=24). Thirty-nine men (67%) underwent prostate MRI, and 35 (60%) had a prostate biopsy. In total, 26 men (45%) underwent local therapy, which included salvage RT in 14 men (54%) [brachytherapy (n=9), SBRT (n=5)], cryotherapy/HIFU in 11 men (42%), and salvage prostatectomy for one (4%). Among the 28 patients (48%) not undergoing local therapy, 32% (n=9) were poor local therapy candidates due to poor GU/GI quality of life or prior focal therapy and received systemic therapy alone. Approximately one-third of patients underwent observation (n=19), driven frequently by patient preference rather than local therapy eligibility or age-related comorbidities (n=12/19). Patient management and treatment varied by the specialty ordering the PSMA and subsequent referral patterns. Our data demonstrate significant heterogeneity in the management of patients with PSMA radiorecurrent localized-only prostate cancer. Treatment varied by ordering physician specialty and subsequent referral patterns after PSMA. As molecular imaging becomes more ubiquitous, our data demonstrate the need for multidisciplinary discussion as well as randomized trials in these patients to help guide the optimal treatment approach for this population. [ABSTRACT FROM AUTHOR]