Cyclophosphamide-associated bladder cancers and considerations for survivorship care: A systematic review

Urol Oncol. 2021 Oct;39(10):678-685. doi: 10.1016/j.urolonc.2021.05.017. Epub 2021 Jun 13.


Purpose: We performed a systematic review to assess the clinical features of cyclophosphamide-associated bladder cancer.

Materials and methods: MEDLINE, Web of Science, and Cochrane Library were searched from inception to August 2020 according to PRISMA guidelines. Studies that associated bladder cancer with prior cyclophosphamide use on an individual level were included.

Results: We identified 121 studies spanning over a 50-year period with 285 patients. The most common malignant indication for cyclophosphamide was lymphoma (25%), while the most common non-malignant indication was ANCA-associated vasculitides (26%). Hematuria and dysuria were the most prevalent symptoms prior to a cyclophosphamide-associated bladder cancer diagnosis, and median age at diagnosis was 55 years. Conventional urothelial carcinoma (UC) was the most common bladder-associated diagnosis (74%), although a broad range of cancer types were represented, notably leiomyosarcoma and squamous cell carcinoma. About half of bladder cancers were muscle invasive at diagnosis and median latency time was 10.0 years; 33% of patients had a bladder cancer related death.

Conclusions: We describe the largest pooled analysis of patients with cyclophosphamide-associated bladder cancer. These bladder cancers have a propensity for younger age at diagnosis, more advanced stage at diagnosis, and variant histology. There was a substantial number of patients with latency time of ≥20 years independent of cumulative cyclophosphamide dose. These findings support consideration of screening and long-term surveillance of cancer survivors with a history of cyclophosphamide therapy for bladder cancer.

Keywords: Cyclophosphamide; Hematuria; Systematic review; Urinary bladder neoplasms.

Publication types

  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Female
  • Humans
  • Male
  • Survival Analysis
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / mortality


  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide