She began by noting the fact that multiple studies have suggested that the rate of pathologic complete response to NAC in patients with UTUC is significantly lower (9-14%) than in patients who receive NAC for primary bladder cancer (PBC) (~38%). The discrepancy between response rates to NAC for UTUC and PBC are not fully understood but may be related to difficulties in accurate staging for UTUC patients or may be related to differences in tumor biology.
Multiple retrospective studies have shown that NAC for UTUC has efficacy in terms of pathologic downstaging in patients with node-positive or metastatic UTUC. NAC also has been retrospectively shown to improve 5-year cancer-specific survival, as well as 5-year overall survival as compared to observation alone in this patient cohort. Dr. Hoffman-Censits then reviewed the retrospective and prospective data for NAC in patients with lymph node-negative UTUC and showed that there is a 3-10% rate of complete pathologic response, as well as a 30-75% rate of tumor downstaging on final pathologic analysis. Furthermore, there are statistically significant improvements in 5-year overall survival rates for patients who received NAC versus observation alone.
Dr. Hoffman-Censits noted that one of the strengths of NAC versus adjuvant chemotherapy after nephroureterectomy is that surgery will render some patients ineligible for cisplatin-based chemotherapy regimens who would have been candidates pre-operatively. Trials have shown that up to 58% of patients are eligible for cisplatin in the neoadjuvant setting, however, this number declines to as low as 15% in the post-nephroureterectomy group. Because of the apparent benefits of cisplatin-based chemotherapy, she feels that while some patients will be overtreated in the neoadjuvant setting, many patients will be able to receive systemic treatment that they otherwise would be ineligible for in the adjuvant setting after nephroureterectomy.
She then outlined the POUT trial which was a phase III randomized clinical trial evaluating the use of perioperative chemotherapy versus observation in patients with high-grade UTUC. POUT showed a trend towards improved disease-free survival in the perioperative chemotherapy group versus observation alone.
She finished by highlighting ongoing clinical trials of perioperative chemotherapy in UTUC. These include a study from Memorial Sloan Kettering Cancer Center which just recently finished accruing patients to receive perioperative gemcitabine and cisplatin. The primary endpoint of this study will be the rate of <pT2N0 disease after perioperative chemotherapy. Finally, the URANUS trial is a phase II clinical trial that will compare patients with cT2-cT4 high-risk UTUC who are randomized to receive either neoadjuvant gemcitabine/cisplatin or MVAC prior to nephroureterectomy, versus adjuvant chemotherapy regimens after nephroureterectomy. She believes that these trials will lend further data to the field and will hopefully help to better inform us of the role of neoadjuvant chemotherapy for this disease.
Presented by: Jean Hoffman-Censits, MD, Johns Hopkins University, Baltimore, Maryland
Written by: Brian Kadow, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, Pennsylvania at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona