The retrospective cohort consisted of 203 patients. After the publication of the initial phase 2 study, there was an increase in the use of neoadjuvant chemotherapy from 48% to 83% (p < 0.001). The distribution of patients into subgroups based on chemotherapy regimen after surgery was as follows: EP (n = 46), IA/EP (n = 63), methotrexate/vinblastine/doxorubicin/cisplatin or gemcitabine/cisplatin (MVAC/GC, n = 11), and other (n = 21). The median number of cycles across regimens was four. Overall, neoadjuvant chemotherapy was associated with a significantly higher rate of pathological complete response (pCR) than initial surgery (49.6% versus 14.5%; p < 0.001). Further, patients who underwent initial surgery had a higher rate of residual NEC than those who received neoadjuvant chemotherapy (74.2% versus 25.5%; p < 0.0001). The proportion of patients who achieved a pCR in the EP versus IA/EP groups was 37% and 60.3%, respectively. An adjusted multivariate logistic model revealed a significant effect of neoadjuvant chemotherapy on pCR (OR = 3.9; 95% CI, 1.6 – 9.6; p = 0.003). IA/EP treatment was the only factor associated with improved downstaging (OR = 3.7; 95% CI, 1.3 – 10.2; p = 0.01). There was no association between the number of cycles and response.
The median follow-up time was 59.7 months (95% CI, 45.5 – 74.5), and the median OS across the cohort was 46.5 mo (95% CI, 35.8 – 72.4). There were 100 deaths overall. Median overall survival (OS) was 86.1 months (95% CI, 57.0 – NA) among patients who received neoadjuvant chemotherapy, 20.6 months (95% CI, 13.9 – 37.6) among those who underwent surgery alone, and 23.5 months (95% CI, 16.2 – NA) among those who underwent surgery followed by adjuvant chemotherapy. The estimated 5-year OS for neoadjuvant chemotherapy followed by surgery, surgery alone, and surgery followed by adjuvant chemotherapy were 57% (95% CI, 48 – 68), 22% (95% CI, 11 – 41), and 30% (95% CI, 14 – 62), respectively. A multivariable-adjusted Cox model demonstrated that neoadjuvant chemotherapy significantly improved OS compared to upfront surgery (HR = 0.3, 95% CI, 0.15 – 0.6; p < 0.001). Furthermore, the NEC regimen (IA/EP or EP) was associated with better median OS than a urothelial regimen (MVAC/GC or others; 145.4 months versus 42.5 months; HR = 0.5; 95% CI, 0.25 – 0.94).
This study strengthens the evidence for using neoadjuvant chemotherapy in patients with NEC-URO. Importantly, the alternating doublet regimen potentially improves tolerability among patients. Limitations of the study include the lack of data regarding adverse events and the effect of non-treatment-related factors on some clinical outcomes, such as the number of dissected lymph nodes.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Alhalabi O, Wilson N, Xiao L, et al. Comparative Effectiveness Analysis of Treatment Strategies for Surgically Resectable Neuroendocrine Carcinoma of the Urinary Tract [published online ahead of print, 2023 Oct 11]. Eur Urol Oncol. 2023;S2588-9311(23)00198-0. doi:10.1016/j.euo.2023.09.004