The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer

BJU Int. 2024 Jul;134(1):119-127. doi: 10.1111/bju.16319. Epub 2024 Mar 12.

Abstract

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection.

Patients and methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression.

Results: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses.

Conclusion: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Keywords: cN+; induction chemotherapy; pathology; survival; urinary bladder neoplasms.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Cisplatin / administration & dosage
  • Cystectomy* / methods
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Induction Chemotherapy*
  • Lymph Node Excision
  • Lymph Nodes / pathology
  • Lymphatic Metastasis*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / mortality
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Gemcitabine
  • Cisplatin
  • Methotrexate
  • Deoxycytidine