Unfortunately, most prospective clinical trials assessing NAC regimens have historically excluded HS, instead focusing on pure urothelial carcinoma, as this makes up the majority of patients diagnosed with MIBC. Furthermore, pathologic response to NAC has been a commonly employed surrogate endpoint in clinical trials, but it is unclear how HS impacts prognosis when stratified by pathologic response to NAC compared with PUC. Accordingly, available guidelines provide little guidance on risk-stratified approaches to NAC in patients with HS.
In this study, we addressed this knowledge gap using the SEER database. Patients diagnosed with MIBC between 2004-2020 who received NAC followed by RC were included. We sought to assess how pathologic response to NAC impacts post-RC survival in patients with HS compared to PUC. For our analysis, pathologic response to NAC was classified as complete response (ypT0N0), partial response (<ypT2N0), and non-response (ypT2-4 or ypN+).
Concordant with prior literature, patients with HS exhibited lower rates of partial and complete response as compared to the PUC patients. Accordingly, patients with PUC had worse post-RC survival compared to PUC. Patients with HS had uniformly worse overall survival even after controlling for pathologic response, with the most notable discrepancy in partial responders (i.e., partial responders with PUC had significantly better overall survival compared with partial responders with HS). Patients with neuroendocrine/small cell differentiation exhibited inferior overall survival when compared with PUC across the spectrum of pathologic response to NAC.
These findings have significant clinical implications. First, they help guide patient counseling with respect to post-RC prognosis in patients with HS and may guide risk-stratified approaches to adjuvant therapy intensification in HS subgroups. Second, these data inform the appropriate use of pathologic response as a surrogate endpoint in clinical trials incorporating patients with HS. While these data do not help definitively answer the question of whether NAC is beneficial for individual HS, they help contextualize prognosis in this often-overlooked patient population.
Written by: Seth L. Teplitsky,1,2 Patrick J. Hensley1
- Department of Urology, University of Kentucky College of Medicine, Lexington, KY, USA
- Department of Urology, Duke University, Durham, NC, USA