Can Bacillus Calmette-Guérin (BCG) treat localized prostate cancer?

Abstract

The Bacillus Calmette-Guérin (BCG) vaccine has been used for a century to prevent tuberculosis and non-specific effects of BCG vaccination have provided a degree of protection from other non-mycobacterial pathogens and even some cancers. As such, intravesical BCG instillation is an accepted and well tolerated immunotherapy for non-muscle-invasive bladder cancer. Notably, during BCG instillations there is commonly reflux of urine from the prostatic urethra into the prostatic ducts and most men develop an asymptomatic granulomatous prostatitis in the peripheral zone of the prostate, typically where prostate cancer occurs. In the United States, prostate cancer is the most common diagnosed cancer in men; and most men are diagnosed over age sixty. There are several treatment options for localized intermediate-risk prostate cancer; they include active surveillance, radical prostatectomy, radiotherapy, and androgen deprivation therapy. However, these treatments can cause urinary, sexual, and rectal toxicities; as such, some older men defer treatment and instead choose watchful waiting, which is associated with a worse survival outcome compared to treatment options. We posit that intravesical BCG can target prostate cancer directly by refluxing from the prostatic urethra via ducts into the peripheral zone of the prostate and at that location initiate a robust immunologic anti-tumor response. Moreover, there is evidence that a prior BCG vaccination will augment the immune response from intravesical BCG therapy. Hence, we hypothesize that BCG vaccination followed by intravesical BCG instillation might be a treatment option for localized intermediate-risk prostate cancer, will have limited side effects, and be particularly suited for older men who have chosen watchful waiting. We have suggested how this hypothesis can be safely tested.