Pathological downstaging as a novel endpoint for the development of neoadjuvant chemotherapy for upper tract urothelial carcinoma

Abstract

Objectives To evaluate whether pathological downstaging (pDS) was more informative in predicting overall survival (OS) than pathological complete response (pCR) in patients treated with neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). Patients and Methods The National Cancer Database was queried for patients with high‐grade cN0M0 disease who had received NAC. pDS was defined as a decrease of at least one stage from cT to pT stage along with pN0, including pCR. A multivariable Cox model predicting OS was generated by fitting alternatively either pDS or pCR, and adjusted for potential confounders. The discrimination of the Cox models for predicting OS was evaluated using Harrell's C‐index. The analyses were repeated in patients diagnosed as having cT2–4N0M0 disease. Results Among 264 patients meeting the inclusion criteria, 72 (27%) and 39 (15%) achieved pDS and pCR, respectively. On multivariable analysis, both pDS (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.13, 0.45; P < 0.001) and pCR (HR 0.37, 95% CI 0.18, 0.79; P = 0.01) were associated with OS. The model including pDS achieved better discrimination with respect to the model including pCR: C‐index 76.4 vs 72.7, respectively. In the 128 patients diagnosed with cT2–4 disease, both pDS (HR 0.19, 95% CI 0.09, 0.40; P < 0.001) and pCR (HR 0.31, 95% CI 0.11, 0.85; P = 0.023) were confirmed as predictors of OS. The model including pDS was confirmed to discriminate better than the model including pCR: C‐index 75 vs 68.9, respectively. Conclusion The study showed that pDS after NAC for UTUC was more informative than pCR when predicting OS. These findings, although requiring prospective validation, can aid in the design of clinical trials seeking to refine the use of chemotherapy and other systemic therapies in this setting.

Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma

“…Recent studies have shown that NAC is associated with higher rates of pDS and pCR and improved RFS, CSS, and OS in patients with locally advanced or node-positive UTUC [15,16]. On the contrary, studies evaluating the role of NAC for localised or cN0M0 UTUC are insufficient [18,19]. To the best of our knowledge, this is the first report to identify the prognostic factors of high-risk UTUC after NAC, and the survival benefit of NAC for high-risk localised disease.…”

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high‐risk upper tract urothelial carcinoma: a multicentre retrospective study

“…2A ). Several studies have suggested that pathological downstaging is a potential endpoint of NAC in UTUC [ 16 , 17 , 28 ]. However, difficulty in making an accurate T stage diagnosis is a strong limitation of pathological downstaging.…”

Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review

“…Based on the observations and results obtained through neoadjuvant chemotherapy in the treatment of bladder carcinoma, several retrospective studies have investigated the role of neoadjuvant therapy in UTUC. Utilizing preoperative cisplatin-based chemotherapy, pathological downstaging as well as lower recurrence rates and better outcomes have been observed (14,(89)(90)(91)(92). To date, no prospective trial has been published on this topic.…”