Downstaging and Survival Associated with Neoadjuvant Immunotherapy Before Radical Cystectomy for Muscle-invasive Bladder Cancer.

BACKGROUND: Neoadjuvant cisplatin-containing chemotherapy before radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). However, a large proportion of patients are ineligible for cisplatin. Single-arm phase 2 neoadjuvant immunotherapy trials have reported promising tumor response rates, but interpretation is limited owing to lack of a comparator arm. OBJECTIVE: To compare rates of pathologic downstaging and overall survival between patients receiving neoadjuvant immunotherapy (NAI), neoadjuvant chemotherapy (NAC), or no neoadjuvant therapy (NNAT). DESIGN, SETTING, AND PARTICIPANTS: We identified 18 483 patients in the National Cancer Data Base who were diagnosed with clinically localized MIBC and underwent radical cystectomy from 2014 to 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Nearest-neighbor propensity-score caliper matching was used to create three demographically similar and equally sized cohorts stratified by NAT receipt. Logistic regression was used to examine the association of treatment received with pathologic downstaging to pT0N0 and pT < 2N0. Cox proportional-hazards regression was used to assess the association of treatment received with overall survival (OS). RESULTS AND LIMITATIONS: Propensity score matching yielded three equally sized cohorts without significant differences in baseline characteristics (n = 840). The NAI group had a higher rate of pathologic downstaging to pT0N0 than the NNAT group and a similar rate to the NAC group (NNAT 6.7% vs NAC 26.4%, odds ratio 5.0, 95% confidence interval [CI] 2.9-8.3; NAI 22.5%, odds ratio 4.0, 95% CI 2.4-7.1). The NAI group had better OS than the NNAT group and similar OS to the NAC group (NAC: hazard ratio 0.62, 95% CI 0.42-0.92; NAI: hazard ratio 0.68, 95% CI 0.46-0.97, with NNAT as the reference). The primary limitation is selection bias from confounding by clinical indication. CONCLUSIONS: NAI is a promising alternative to NAC for patients with clinically localized MIBC, as evidenced by similar pathologic downstaging rates and OS benefits in comparison to no NAT. Phase 3 trials should be conducted to test the noninferiority of NAI to NAC. PATIENT SUMMARY: We compared outcomes for patients with muscle-invasive bladder cancer according to whether they received chemotherapy, immunotherapy, or no medical therapy before surgical removal of their bladder. We found that preoperative immunotherapy improved patient survival and regression of the cancer stage in comparison to no medical therapy, similar to the outcomes seen with preoperative chemotherapy. Randomized clinical trials are needed to confirm these findings.

Selecting patients for magnetic resonance imaging cognitive versus ultrasound fusion biopsy of the prostate: A within-patient comparison.

Objectives: To compare overall agreement between magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) and MRI cognitive fusion biopsy (CB) of the prostate and determine which factors affect agreement for prostate cancer (PCa) who underwent both modalities in a prospective within-patient protocol. Patients and Methods: From August 2017 to January 2021, patients with at least one Prostate Imaging Reporting & Data System (PI-RADS) 3 or higher lesion on multiparametric MRI underwent transrectal FB and CB in a prospective within-patient protocol. CB was performed for each region of interest (ROI), followed by FB, followed by standard 12 core biopsy. Patients who were not on active surveillance were analysed. The primary endpoint was agreement for any PCa detection. McNemar's test and kappa statistic were used to analyse agreement. Chi-square test, Fisher's exact test and Wilcoxon rank sum test were used to analyse disagreement across clinical and MRI spatial variables. A multivariable generalized mixed-effect model was used to compare the interaction between select variables and fusion modality. Statistics were performed using SAS and R. Results: Ninety patients and 98 lesions were included in the analysis. There was moderate agreement between FB and CB (k = 0.715). McNemar's test was insignificant (p = 0.285). Anterior location was the only variable associated with a significant variation in agreement, which was 70% for anterior lesions versus 89.7% for non-anterior lesions (p = 0.035). Discordance did not vary significantly across other variables. In a mixed-effect model, the interaction between anterior location and use of FB was insignificant (p = 0.411). Conclusion: In a within-patient protocol of patients not on active surveillance, FB and CB performed similarly for PCa detection and with moderate agreement. Anterior location was associated with significantly higher disagreement, whereas other patient and lesion characteristics were not. Additional studies are needed to determine optimal biopsy technique for sampling anterior ROI.