Study Identifies Patients With Muscle-Invasive Bladder Cancer Who Benefit Most From Neoadjuvant Chemotherapy

Patients with nonluminal tumors with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy prior to radical cystectomy had greater overall survival (OS) at 3 years and better cancer-specific survival (CSS) than those patients who did not receive neoadjuvant chemotherapy, according to a recent study. Additionally, patients with muscle-invasive bladder cancer with luminal tumors derived little to no survival benefits from neoadjuvant chemotherapy prior to radical cystectomy.

The study included a total of 601 patients with muscle-invasive bladder cancer who underwent radical cystectomy and had genomic data available from transurethral resection of bladder tumor samples, combined from 4 bladder cancer cohorts from multiple institutions. There were 247 patients who had been treated with neoadjuvant chemotherapy before radical cystectomy, while 354 underwent radical cystectomy without neoadjuvant chemotherapy. Genomic subtyping classifier (GSC) scores for all specimens were generated using a commercially available clinical-grade whole-transcriptome assay. Patients were stratified based on luminal vs nonluminal (basal, claudin-low, and luminal infiltrated) tumors. The primary end point of the study was OS, and the secondary end point was CSS.

The median follow-up duration was 2.5 years for those in the neoadjuvant chemotherapy groups and 2.9 years in the non-neoadjuvant chemotherapy groups. Patients with luminal tumors who received neoadjuvant chemotherapy had an OS of 82% and 63% at 2 and 3 years respectively, which was comparable to those treated without neoadjuvant chemotherapy (OS of 78% and 65% at 2 and 3 years respectively). However, patients with nonluminal tumors who received neoadjuvant chemotherapy had an OS of 78% and 71%, at 2 and 3 years respectively, while patients with nonluminal tumors who did not receive neoadjuvant chemotherapy had an OS of 69% and 61% at 2 and 3 years respectively.

Results of the multivariable analysis showed that neoadjuvant chemotherapy was associated with significantly improved OS among patients with nonluminal tumors (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.44 to 0.98; P = .04). However, patients with luminal tumors did not experience this benefit (HR, 0.91; 95% CI, 0.50 to 1.63, P = .74).”

There were similar results for CSS, as study authors wrote, “receipt of [neoadjuvant chemotherapy] was not associated with improved outcomes among the luminal subset of patients. In contrast patients with nonluminal tumors were noted to have an 11% survival advantage at 3 years with [neoadjuvant chemotherapy] (77% vs 66%).”

Multivariable analysis supported these findings, showing no benefit of NAC for luminal tumors (HR, 1.11; 95% CI, 0.38 to 0.93; P = .02), while nonluminal tumors benefited significantly (HR, 0.59; 95% CI, 0.38 to 0.93, P = .02).

The study authors concluded that, “based on whole transcriptome profiling, nonluminal tumors received the greatest benefit from [neoadjuvant chemotherapy], while patients with luminal tumors experience little or no survival benefit from [neoadjuvant chemotherapy].” The authors went on to suggest that “utilizing a genome classifier to select [muscle-invasive bladder cancer] patients for [neoadjuvant chemotherapy] could enrich for patients most likely to benefit while identifying patients who may not benefit from additional treatments.”

Source:

Lotan Y, de Jong JJ, Liu VYT, et al. Patients with muscle-invasive bladder cancer with nonluminal subtype derive greatest benefit from platinum based neoadjuvant chemotherapy. J Urol. Published Online March 1, 2022. doi:10.1097/JU.0000000000002261