TY - JOUR
T1 - Comparative Effectiveness Analysis of Treatment Strategies for Surgically Resectable Neuroendocrine Carcinoma of the Urinary Tract
AU - Alhalabi, Omar
AU - Wilson, Nathaniel
AU - Xiao, Lianchun
AU - Lin, Yiyun
AU - Khandelwal, Jaanki
AU - Moussa, Mohammad Jad
AU - Msaouel, Pavlos
AU - Navai, Neema
AU - Gao, Jianjun
AU - Kamat, Ashish M.
AU - Pilie, Patrick
AU - Shah, Amishi Y.
AU - Goswami, Sangeeta
AU - Matin, Surena
AU - Kovitz, Craig
AU - Holla, Vijaykumar
AU - Guo, Charles
AU - Czerniak, Bogdan
AU - Logothetis, Christopher
AU - Corn, Paul G.
AU - Dinney, Colin P.N.
AU - Campbell, Matthew T.
AU - Hansel, Donna E.
AU - Tannir, Nizar M.
AU - Siefker-Radtke, Arlene O.
N1 - Publisher Copyright:
Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - BACKGROUND: Neoadjuvant chemotherapy (neoCTX) has been recommended as the optimal strategy in surgically resectable neuroendocrine carcinoma (NEC) of the urinary tract (NEC-URO). OBJECTIVE: To determine the systemic therapy regimen and timing, which are most active against NEC-URO. DESIGN, SETTING, AND PARTICIPANTS: We used our institutional historical clinical and pathological database to study 203 patients (cT2, 74%; cT3/4a, 22%; and cTx, 4%) with surgically resectable NEC-URO between November 1985 and May 2020. A total of 141 patients received neoCTX and 62 underwent initial radical surgery, 24 of whom received adjuvant CTX (adjCTX). INTERVENTION: Neoadjuvant CTX with etoposide/cisplatin (EP), an alternating doublet of ifosfamide/doxorubicin (IA) and EP, dose-dense methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), gemcitabine/cisplatin (GC), or others. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), downstaging rate, and pathological complete response using a multivariable model adjusting for tumor- and patient-related factors. RESULTS AND LIMITATIONS: Downstaging rate was significantly improved with neoCTX versus initial surgery (49.6% vs 14.5%, p < 0.0001), stage cT2N0 versus cT3/4N0 (44% vs 25%, p = 0.01), or presence of carcinoma in situ (47% vs 28%, p = 0.01). Downstaging was greatest with IA/EP (65%) versus EP (39%), MVAC/GC (27%), or others (36%, p = 0.04). After adjusting for age and Eastern Cooperative Oncology Group performance status, IA/EP was still associated with improved downstaging (odds ratio = 3.7 [1.3-10.2], p = 0.01). At a median follow-up of 59.7 mo, 5-yr OS rates for neoCTX followed by surgery, surgery alone, and surgery followed by adjCTX were 57%, 22%, and 30%, respectively. An NEC regimen (IA/EP or EP) versus a urothelial regimen (MVAC/GC or others) was associated with improved survival (145.4 vs 42.5 mo, hazard ratio = 0.49, 95% confidence interval: 0.25-0.94). CONCLUSIONS: Neoadjuvant CTX remains the standard-of-care treatment for NEC-URO with an advantage for NEC regimens over traditional urothelial regimens. IA/EP improves pathological downstaging at the time of surgery compared with EP, but is reserved for younger and higher function patients. PATIENT SUMMARY: In this report, we looked at the outcomes from invasive neuroendocrine carcinoma of the urinary tract in a large US population. We found that the outcomes varied with treatment strategy. We conclude that the best outcomes are seen in patients treated with chemotherapy prior to surgery and regimens tailored to histology and tolerance.
AB - BACKGROUND: Neoadjuvant chemotherapy (neoCTX) has been recommended as the optimal strategy in surgically resectable neuroendocrine carcinoma (NEC) of the urinary tract (NEC-URO). OBJECTIVE: To determine the systemic therapy regimen and timing, which are most active against NEC-URO. DESIGN, SETTING, AND PARTICIPANTS: We used our institutional historical clinical and pathological database to study 203 patients (cT2, 74%; cT3/4a, 22%; and cTx, 4%) with surgically resectable NEC-URO between November 1985 and May 2020. A total of 141 patients received neoCTX and 62 underwent initial radical surgery, 24 of whom received adjuvant CTX (adjCTX). INTERVENTION: Neoadjuvant CTX with etoposide/cisplatin (EP), an alternating doublet of ifosfamide/doxorubicin (IA) and EP, dose-dense methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), gemcitabine/cisplatin (GC), or others. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), downstaging rate, and pathological complete response using a multivariable model adjusting for tumor- and patient-related factors. RESULTS AND LIMITATIONS: Downstaging rate was significantly improved with neoCTX versus initial surgery (49.6% vs 14.5%, p < 0.0001), stage cT2N0 versus cT3/4N0 (44% vs 25%, p = 0.01), or presence of carcinoma in situ (47% vs 28%, p = 0.01). Downstaging was greatest with IA/EP (65%) versus EP (39%), MVAC/GC (27%), or others (36%, p = 0.04). After adjusting for age and Eastern Cooperative Oncology Group performance status, IA/EP was still associated with improved downstaging (odds ratio = 3.7 [1.3-10.2], p = 0.01). At a median follow-up of 59.7 mo, 5-yr OS rates for neoCTX followed by surgery, surgery alone, and surgery followed by adjCTX were 57%, 22%, and 30%, respectively. An NEC regimen (IA/EP or EP) versus a urothelial regimen (MVAC/GC or others) was associated with improved survival (145.4 vs 42.5 mo, hazard ratio = 0.49, 95% confidence interval: 0.25-0.94). CONCLUSIONS: Neoadjuvant CTX remains the standard-of-care treatment for NEC-URO with an advantage for NEC regimens over traditional urothelial regimens. IA/EP improves pathological downstaging at the time of surgery compared with EP, but is reserved for younger and higher function patients. PATIENT SUMMARY: In this report, we looked at the outcomes from invasive neuroendocrine carcinoma of the urinary tract in a large US population. We found that the outcomes varied with treatment strategy. We conclude that the best outcomes are seen in patients treated with chemotherapy prior to surgery and regimens tailored to histology and tolerance.
KW - Cisplatin
KW - Etoposide
KW - Ifosfamide
KW - Large cell carcinoma
KW - Neuroendocrine
KW - Neuroendocrine carcinoma
KW - Small cell carcinoma
KW - Systemic therapy
KW - Urothelial cancer
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U2 - 10.1016/j.euo.2023.09.004
DO - 10.1016/j.euo.2023.09.004
M3 - Article
C2 - 37833193
AN - SCOPUS:85178651043
SN - 2588-9311
VL - 6
SP - 611
EP - 620
JO - European Urology Oncology
JF - European Urology Oncology
IS - 6
ER -