Neoadjuvant Chemotherapy Significantly Improves OS for Low-Risk, Basal Bladder Cancer

Jonathan Duplisea, MD

Treatment with neoadjuvant chemotherapy prior to radical cystectomy significantly improved overall survival (OS) compared with cystectomy alone for patients with the basal subtype of muscle-invasive bladder cancer (MIBC), according to findings from a 165-patient study presented at the 2017 SUO Annual Meeting.

In the study, OS was dramatically improved with neoadjuvant chemotherapy for patients with basal tumors, regardless of whether they had high-risk or low-risk MIBC (P <.0001). In a multivariate analysis correcting for age, male gender, and stage, there was an 86.5% reduction in the risk of death with the addition of neoadjuvant chemotherapy compared with cystectomy alone for patients with the basal subtype (HR, 0.135; 95% CI, 0.0454-0.399; P <.0001). There was no survival advantage when looking at the luminal (P = .5768) or p53-like subtypes (P = .9754) with neoadjuvant chemotherapy.

“There was a significant survival advantage noted in basal tumors that received neoadjuvant chemotherapy. This held true in a multivariate analysis that was statistically significant,” Jonathan Duplisea, MD, a urology fellow at the University of Texas MD Anderson Cancer Center, said during a presentation of the results. “In this particular cohort of patients, survival of low-risk patients is improved by neoadjuvant chemotherapy. This benefit appears to be confined to basal tumors.”

Neoadjuvant chemotherapy is known to play a role in the treatment of MIBC prior to cystectomy; however, widespread adoption of this treatment strategy has not occurred, with some papers finding that around 20% of patients end up getting neoadjuvant chemotherapy. Commonly cited reasons for this lack of adoption are concerns about the toxicity and not wanting to delay surgery.

The trial included 165 patients with MIBC who were treated with radical cystectomy with or without neoadjuvant chemotherapy at MD Anderson or the University of British Columbia. Patients were classified as high or low clinical risk, based on hydroureteronephrosis, clinical T3a to T4b disease, histologic evidence of lymphovascular invasion (LVI), and micropapillary or neuroendocrine features at the time of transurethral resection. Whole genome analysis was performed on transurethral resection specimens classifying them as luminal, basal, or p53-like.

Patients were a median age of 65 years (range, 35-89), with 68% classified as high risk and 32% as low risk. In terms of disease state and clinical features, 27% had ≥T3b disease, LVI was identified in 21% of patients, hydroureteronephrosis in 29%, and 16% had variant histology. There was relatively even distribution of the subtypes, with 30% basal, 39% p53-like, and 31% luminal. “Importantly, there were no differences in the subtypes with respect to age, sex, and stage,” Duplisea noted.

Across all enrolled patients, there was a distinct OS advantaged in patients with clinically high-risk disease with neoadjuvant chemotherapy compared with radical cystectomy alone, with a 49% reduction in the risk of death in the neoadjuvant arm after more than 200 months of follow-up (HR, 0.511; 95% CI, 0.297-0.876; P = .015). Additionally, an improvement in OS was also seen with neoadjuvant chemotherapy in the low-risk population (HR, 0.101; 95% CI, 0.0135-0.758; P = .026).

Looking at subtype and clinical risk stratification, in the high-risk patients with basal tumors, there was a distinct survival advantage, Duplisea noted. With nearly 300 months of follow-up, 25% of patients in the neoadjuvant chemotherapy arm remained alive versus none in the surgery-alone group (P = .0014). In the low-risk, basal population, 100% of patients who received neoadjuvant chemotherapy remained alive compared with approximately 20% of those who did not receive neoadjuvant therapy (P = .0082).

“If we did not know the subtypes of these patients, they would have been classified as low-risk, and not received chemotherapy using our risk-stratified approach,” Duplisea said. “Despite the small number that we had, once we dissected everything down in terms of risk stratification and subtype, we believe that the definition of high-risk should be emended to include the basal subtype,” he concluded.

Duplisea J, Metcalfe M, Sundi D, et al. Combining clinical risk features and intrinsic molecular subtypes to refine selection criteria for neoadjuvant chemotherapy in patients with muscle invasive bladder cancer. Abstract presented at: 2017 SUO Annual Meeting; November 29-December 1, 2017; Washington, DC. Oral abstract podium #4.