The Impacts of Intravesical Bacillus Calmette–Guérin (BCG) Therapy on Male Fertility in Non-Muscle-Invasive Bladder Cancer (NMIBC): A Narrative Review
DOI:
https://doi.org/10.59784/glosains.v7i2.678Keywords:
Bacillus Calmette–Guérin, non–muscle-invasive bladder cancer, intravesical therapy, sperm parameters, male fertility, gonadotoxicityAbstract
Background: Intravesical Bacillus Calmette–Guérin (BCG) is the current gold standard adjuvant therapy to reduce both recurrence and progression of non-muscle-invasive bladder cancer (NMIBC). On the other hand, there is a growing concern about its possible effect on male fertility.
Objective: This narrative review provides an analysis of the recent evidence regarding the impact of intravesical BCG therapy on semen quality and overall male fertility parameters in reproductive-age NMIBC patients.
Methods: A targeted literature review was performed for prospective clinical studies assessing semen parameters and reproductive hormones before and after intravesical therapy. A narrative review was conducted that included studies eligible for inclusion (up to date through October 2023) to describe comparative changes in semen quality and endocrine function by comparing BCG-treated men with matched cohorts following exposure.
Results: Intravesical BCG was associated with decreased sperm concentration and motility, in some cases with progression to oligospermia and abnormal sperm morphology including "amorphous" heads, bent necks, and short tails—although results were inconsistent. Although early studies found stable hormonal profiles, recent data have shown increases in follicle-stimulating hormone and testosterone, indicating testicular stress with compensatory feedback mechanisms. Conversely, no adverse reproductive effects were observed with mitomycin C.
Conclusions: Intravesical BCG may transiently interfere with spermatogenesis while endocrine function remains intact. These results underline the importance of fertility counseling and semen cryopreservation before intravesical therapy. This needs to be confirmed in larger studies with longer follow-up periods for reproductive outcomes.
References
Asín, M. A. P.-J., Fernández-Ruiz, M., López-Medrano, F., Lumbreras, C., Tejido, A., San Juan, R., Arrebola-Pajares, A., Lizasoain, M., Prieto, S., & Aguado, J. M. (2014). Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature. Medicine, 93(17), 236–254. https://doi.org/10.1097/MD.0000000000000119
Böhle, A., & Bock, P. R. (2004). Intravesical bacille Calmette-Guerin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology, 63(4), 682–686. https://doi.org/10.1016/j.urology.2003.11.049
Deininger, S., Törzsök, P., Mitterberger, M., Pallauf, M., Oswald, D., Deininger, C., & Lusuardi, L. (2022). From interferon to checkpoint inhibition therapy—A systematic review of new immune-modulating agents in Bacillus Calmette–Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC). Cancers, 14(3), 694.
Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., & Bray, F. (2021). Global cancer observatory: cancer today. Lyon: International Agency for Research on Cancer; 2020. Cancer Tomorrow.
Fuge, O., Vasdev, N., Allchorne, P., & Green, J. S. A. (2015). Immunotherapy for bladder cancer. Research and Reports in Urology, 65–79. https://doi.org/10.2147/RRU.S63447
Garg, M., Sankhwar, S. N., Goel, A., Kumar, M., Singh, B. P., Singh, V., Dalela, D., Kumar, A., & Paul, S. (2014). Effect of intravesical immunotherapy on sperm parameters in young patients with non–muscle-invasive bladder carcinoma: prospective analysis. Clinical Genitourinary Cancer, 12(3), e83–e86. https://doi.org/10.1016/j.clgc.2013.11.012
Green, D. B., Kawashima, A., Menias, C. O., Tanaka, T., Redelman-Sidi, G., Bhalla, S., Shah, R., & King, B. F. (2019). Complications of intravesical BCG immunotherapy for bladder cancer. Radiographics, 39(1), 80–94.
Kliemann, N., Al Nahas, A., Vamos, E. P., Touvier, M., Kesse-Guyot, E., Gunter, M. J., Millett, C., & Huybrechts, I. (2022). Ultra-processed foods and cancer risk: from global food systems to individual exposures and mechanisms. British Journal of Cancer, 127(1), 14–20.
Lamm, D. L., Blumenstein, B. A., Crawford, E. D., Montie, J. E., Scardino, P., Grossman, H. B., Stanisic, T. H., Smith Jr, J. A., Sullivan, J., & Sarosdy, M. F. (1991). A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette–Guerin for transitional-cell carcinoma of the bladder. New England Journal of Medicine, 325(17), 1205–1209.
Low, L. S., Scholtz, D., Leyland, J., & Nair, S. M. (2021). A severe complication of intravesical bacillus Calmette-Guerin: An effect of different strains. Urology Case Reports, 36, 101592. https://doi.org/10.1016/j.eucr.2021.101592
Lutkiewicz, K., Bieleninik, Ł., Kaloeti, D. V. S., & Bidzan, M. (2023). Reproductive health and well-being from a life span perspective. In Frontiers in Psychology (Vol. 14, p. 1289603). Frontiers Media SA.
Marić, T., Fučić, A., & Aghayanian, A. (2021). Environmental and occupational exposures associated with male infertility. Archives of Industrial Hygiene and Toxicology, 72(2), 101.
Matulay, J. T., Soloway, M., Witjes, J. A., Buckley, R., Persad, R., Lamm, D. L., Boehle, A., Palou, J., Colombel, M., & Brausi, M. (2020). Risk‐adapted management of low‐grade bladder tumours: recommendations from the International Bladder Cancer Group (IBCG). BJU International, 125(4), 497–505.
Morales, A., Eidinger, D., & Bruce, A. W. (2017). Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. The Journal of Urology, 197(2S), S142–S145.
Ng, C. F., Enikeev, D., Vasdev, N., Ekin, G., Sousa, A., Leon, J., Guerrero-Ramos, F., Tan, W. S., Kelly, J., & Shariat, S. F. (2022). Background: The efficacy of intravesical chemotherapy maintenance for patients with non-muscle invasive bladder cancer (NMIBC) is inferior compared to intravesical bacillus Calmette–Guerin (BCG). How intravesical chemohyperthermia (CHT) compares with BCG is under investigation. Objective: To compare the oncological outcomes and safety profile between intravesical. Recent Advances in Bladder Cancer Diagnosis and Treatment, 77552758.
Powles, T., Bellmunt, J., Comperat, E., De Santis, M., Huddart, R., Loriot, Y., Necchi, A., Valderrama, B. P., Ravaud, A., & Shariat, S. F. (2022). Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology, 33(3), 244–258. https://doi.org/10.1016/j.annonc.2021.11.012
Raviv, G., Pinthus, J. H., Shefi, S., Mor, Y., Kaufman-Francis, K., Levron, J., Weissenberg, R., Ramon, J., & Madgar, I. (2005). Effects of intravesical chemotherapy and immunotherapy on semen analysis. Urology, 65(4), 765–767.
Redelman-Sidi, G., Glickman, M. S., & Bochner, B. H. (2014). The mechanism of action of BCG therapy for bladder cancer—a current perspective. Nature Reviews Urology, 11(3), 153–162. https://doi.org/10.1038/nrurol.2014.15
Sahin, S., Ulus, I., Canitez, I. O., Yentur, S., Temiz, M. Z., & Semercioz, A. (2025). The effect of intravesical Bacillus Calmette-Guerin (BCG) treatment on sperm parameters in non-muscle-invasive bladder cancer patients. Basic and Clinical Andrology, 35(1), 17. https://doi.org/10.1186/s12610-025-00259-0
Sylvester, R. J., van der MEIJDEN, A. P. M., & Lamm, D. L. (2002). Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. The Journal of Urology, 168(5), 1964–1970.
Van Hoogstraten, L. M. C., Vrieling, A., van der Heijden, A. G., Kogevinas, M., Richters, A., & Kiemeney, L. A. (2023). Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice. Nature Reviews Clinical Oncology, 20(5), 287–304.
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