TY - JOUR
T1 - Carboplatin Induction Chemotherapy in Clinically Lymph Node–positive Bladder Cancer
AU - von Deimling, Markus
AU - Mertens, Laura S.
AU - van Rhijn, Bas W. G.
AU - Lotan, Yair
AU - Spiess, Philippe E.
AU - Daneshmand, Siamak
AU - Black, Peter C.
AU - Pallauf, Maximilian
AU - D'Andrea, David
AU - Moschini, Marco
AU - Soria, Francesco
AU - del Giudice, Francesco
AU - Afferi, Luca
AU - Laukhtina, Ekaterina
AU - Yanagisawa, Takafumi
AU - Kawada, Tatsushi
AU - Teoh, Jeremy Y. -C.
AU - Abufaraj, Mohammad
AU - Ploussard, Guillaume
AU - Roumiguié, Mathieu
AU - Karakiewicz, Pierre I.
AU - Babjuk, Marko
AU - Gontero, Paolo
AU - Xylinas, Evanguelos
AU - Rink, Michael
AU - Shariat, Shahrokh F.
AU - Pradere, Benjamin
N1 - Funding Information: Financial disclosures: Shahrokh F. Shariat certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Philippe E. Spiess serves as a vice-chair of the National Comprehensive Cancer Network guidelines panel for bladder and penile cancer. Maximilian Pallauf has received a research grant from the Austrian Urological Association, support for attending the Austrian Urological Association yearly meeting, speaker honoraria from Astellas, Janssen, and MedMedia, and an honorarium from Spectra for attending an advisory board; he was a board member for the Austrian Urological Association from 2018 to 2021. Shahrokh F. Shariat has received honoraria from Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, and Takeda; has a consulting or advisory role for Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, and Takeda; and participates in speaker bureaus for Astellas, AstraZeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, and Takeda. The remaining authors have nothing to disclose. Publisher Copyright: © 2023 The Author(s)
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.
AB - Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.
KW - Carboplatin
KW - Induction chemotherapy
KW - Oligometastatic
KW - Survival
KW - Urinary bladder neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85150862796&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.euros.2023.02.014
DO - https://doi.org/10.1016/j.euros.2023.02.014
M3 - Article
C2 - 37187719
SN - 2666-1691
VL - 51
SP - 39
EP - 46
JO - European urology open science
JF - European urology open science
ER -