AUA 2018: Prognostic Impact of Bleomycin Pulmonary Toxicity on the Outcome of Patients with Testicular Cancer

San Francisco, CA ( Dating back to the 1980’s, bleomycin, etoposide and cisplatin (BEP) chemotherapy has been the standard of care for treatment of patients with metastatic testicular cancer. The pulmonary side effects of bleomycin are well-established. A recent review highlighted that bleomycin toxicity is associated with: (i) cumulative bleomycin dose, (ii) renal function, (iii) age, and (iv) smoking status [1].

However, the prognostic impact of bleomycin pulmonary toxicity, along with the impact of removal of bleomycin from further chemotherapy on overall survival (OS) and progression-free survival (PFS) in testicular cancer patients, remains unclear. As such, Yuki Maruyama, MD and colleagues from Japan presented their findings assessing the prognostic impact of bleomycin toxicity on outcomes among patients with testicular cancer.

The authors identified 52 testis cancer patients who underwent a BEP chemotherapy regimen from 2008 to 2017 at a single institution. Patients receiving chemotherapy at another institution were excluded. A retrospective analysis of both the risk factors and the prognostic effect of bleomycin pulmonary toxicity was performed. Bleomycin pulmonary toxicity was defined as patients who removed bleomycin from their regimen for the presence of pulmonary symptoms or interstitial pneumonia on CT imaging without infection. Patients were subsequently divided into two groups: a bleomycin pulmonary toxicity group and a non- bleomycin pulmonary toxicity group for comparison purposes. The Kaplan-Meier method was used to estimate OS and PFS, and differences were tested using the log-rank test. Predictors of bleomycin pulmonary toxicity were analyzed using logistic regression analysis.

The median age of included patients was 34.2 years and median body mass index (BMI) was 22.8 kg/m2. There were 20 patients who had a smoking history, 37 patients were diagnosed with non-seminoma germ cell tumor, and 20 patients had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified in the bleomycin pulmonary toxicity group and 37 patients were in the non-bleomycin pulmonary toxicity group, respectively. Only BMI < 22 was a predictor of bleomycin pulmonary toxicity on multivariable logistic regression modeling (OR 5.63, 95%CI 1.30-24.3). Interestingly, age or cumulative bleomycin dose did not have a significant impact on the development of bleomycin pulmonary toxicity. The presence of bleomycin pulmonary toxicity had no significant impact on both 5-year OS and PFS:
bleomycin pulmonary toxicity AUA2018
The strength of the current study is the dogmatic tracking of bleomycin toxic events in order to perform this institutional analysis. A possible limitation of the current study is a seemingly lack of power to detect cumulative BEP dose as a predictor of bleomycin pulmonary toxicity, which would intuitively seem like a predictor of toxicity. Certainly, the underlying reasons for low BMI leading to the development of bleomycin pulmonary toxicity deserve further consideration to explain the observed effect. Dr. Maruyama concluded that although bleomycin pulmonary toxicity may cause significant downstream morbidity, it does not appear to influence survival outcomes in this institutional analysis. 

1. Haugnes HS, Olderburg J, Bremnes RM. Pulmonary and cardiovascular toxicity in long-term testicular cancer survivors. Urol Oncol 2015;33(9):399-406.

Presented by: Yuki Maruyama, MD Okayama University, Graduate School of Medicine, Okayama, Japan
Co-Authors: Takuya Sadahira, Yosuke Mitsui, Atsushi Takamoto, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Okayama, Japan

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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