Clinical Impact of the CARMENA Trial on Cytoreductive Nephrectomy Practices in the USA: A Difference-in-differences Analysis.

BACKGROUND AND OBJECTIVE: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA. METHODS: Patients were identified in the National Cancer Database from 2004 to 2020. A quasiexperimental difference-in-differences analysis was used to test the primary outcome, as follows: the change in CN rate was assessed among metastatic clear cell renal cell carcinoma (ccRCC) patients diagnosed before versus after 2018, while using the localized nephrectomy (LN) rate performed in the setting of nonmetastatic ccRCC as a control group. KEY FINDINGS AND LIMITATIONS: The difference-in-differences analysis identified a statistically significant decrease in CN rate after CARMENA (ß-coefficient [standard error]: -0.06 [0.025], p = 0.028), with a 10.2% absolute and a 31.8% relative rate reduction when compared with the counterfactual (expected) value (34.7% â†’ 21.9% [actual] vs 32.1% [expected]). Primarily, relative differences in CN and LN rates before and after 2018 may be attributable to additional factors, aside from CARMENA publication, not tested in this quasiexperimental model. CONCLUSIONS AND CLINICAL IMPLICATIONS: CN rates decreased significantly after the publication of the CARMENA trial in 2018, with a minimal difference in regional or demographic practice patterns. Overall, the publication of the CARMENA trial results is seemingly associated with substantial alteration of clinical practice in the USA, with relatively broad and nonspecific adoption across facilities, regions, and demographics. PATIENT SUMMARY: For decades, the immediate surgical removal of the kidney tumor (cytoreductive nephrectomy) was a mainstay of metastatic kidney cancer treatment. In 2018, the CARMENA study showed that patients treated with systemic therapy alone had similar outcomes to patients who underwent cytoreductive nephrectomy first. In this study, we show that fewer cytoreductive nephrectomies were performed after the CARMENA trial results were published.

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.