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 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/5
Y1 - 2023/5
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
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U2 - 10.1016/j.euros.2023.02.014
DO - 10.1016/j.euros.2023.02.014
M3 - Article
C2 - 37187719
AN - SCOPUS:85150862796
SN - 2666-1691
VL - 51
SP - 39
EP - 46
JO - European Urology Open Science
JF - European Urology Open Science
ER -