medwireNews: Neoadjuvant chemotherapy prior to radical cystectomy is likely to benefit patients with non-luminal muscle-invasive bladder cancer (MIBC), but not those with luminal tumors, suggests a retrospective analysis.
“MIBC is a heterogeneous disease with noted highly variable responses in patients to [neoadjuvant chemotherapy], including patients who experience little or no benefit to potentially toxic therapy,” explain Yair Lotan (University of Texas Southwestern Medical Center, Dallas, USA) and fellow researchers.
They add, however, that the current data “strongly suggest that classification of patients based on molecular subtypes could inform patient and clinician decision-making regarding the benefit of [neoadjuvant chemotherapy], which could offer an improvement over the current uniform recommendation of [neoadjuvant chemotherapy] for all patients with MIBC.”
The study investigators drew on four cohorts from different institutions to identify 601 patients with MIBC who underwent radical cystectomy, 247 of whom received neoadjuvant chemotherapy prior to surgery while 354 did not. They then used a commercial genomic classifier to determine patients’ molecular subtypes, finding that of those who received neoadjuvant chemotherapy, 68.8% had non-luminal tumors and 31.2% had luminal tumors, with corresponding rates of 58.8% and 41.2% among those who did not receive chemotherapy.
After applying inverse probability treatment weighting, the 3-year overall survival (OS) rate in the non-luminal tumor subgroup was significantly higher among patients who did versus did not receive neoadjuvant chemotherapy, at 71% and 61%, respectively.
By contrast, there was no significant difference in 3-year OS between patients with luminal tumors who were given neoadjuvant chemotherapy and those who were not, at rates of 63% and 65%, respectively.
And multivariable analysis adjusting for age, sex, and clinical stage showed a significant association between use of neoadjuvant chemotherapy and improved OS in patients with non-luminal MIBC (hazard ratio [HR]=0.66), but not those with luminal disease.
A similar pattern of results was seen for cancer-specific survival (CSS), with significantly higher 3-year CSS rates in non-luminal patients who did versus did not receive neoadjuvant chemotherapy, at 77% and 66%, respectively, and an HR in multivariable analysis of 0.59. Meanwhile, CSS was comparable for patients with luminal MIBC regardless of receipt of neoadjuvant chemotherapy.
Lotan et al conclude in The Journal of Urology: “While the cohort in our study was assembled based on available data and is not derived from a clinical trial, it still suggests that if a genomic classifier were used to select patients for [neoadjuvant chemotherapy] in a population with similar subtype distribution, then 60% of patients selected to receive [neoadjuvant chemotherapy] (non-luminal tumors) may have a survival benefit if provided this therapy.”
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