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Focal Therapy of Prostate Cancer—The Challenge

Focal Therapy of Prostate Cancer—The Challenge

Physicians specializing in urology, as well as industry and the US Food and Drug Administration, face tremendous challenges in the management of prostate cancer. There is conflicting evidence that screening saves lives, and the impact of treatment for localized cancer is small: the number of men needed to screen with prostate-specific antigen (PSA) testing to prevent a death is in the thousands and, at most, 1 man in 20 who is treated will avoid metastasis or death from the disease. The additional challenge is the ubiquity of the disease and the aging of the population; if this were a singular national focus, we could direct a vast proportion of healthcare resources to make a relatively small impact.

My interpretation of the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Prostate Cancer Intervention Versus Observation Trial (PIVOT), and Scandinavian randomized trials (the first two for screening and the latter two for treatment), in combination with the evidence from adjuvant therapy trials, is that the diagnosis and treatment of a high-grade prostate cancer are likely to have a net benefit for the patient, as it is more likely to be a disease that will lead to morbidity and mortality. On the other hand, a low-grade, low-volume tumor most commonly will not progress, and death from this disease is distinctly infrequent regardless of the treatment chosen.

Against this backdrop, we examine focal therapy. The ideal utilization of focal therapy is to treat a smaller prostate cancer in which you can ablate, excise, or render inconsequential a tumor that affects a relatively small fraction of the gland. The problem with this is that most of the time, the tumors that are small and amenable to focal therapies are those that are least likely to harm the patient during his lifetime. On the other hand, high-grade tumors are most often larger tumors (or soon will be larger tumors). It is for these tumors that our evidence suggests the greatest benefit of multimodality therapy (eg, radiation plus hormones or surgery plus adjuvant radiation). As such, the ideal tumor for focal therapy is a tumor that is often left alone, while the tumor we really need to treat is the one for which a focal therapy has a tremendously high bar and, if it is unsuccessful, the patient is at risk for recurrence of an aggressive tumor, progression, and death from the disease.

This is the dilemma of focal therapy. That we have methods to ablate regions of a solid organ in the human body is not a rationale for a treatment: we must ensure that we ultimately provide a benefit to the patient. It will require carefully planned prospective trials with the investment of hundreds of patients and years of follow-up to ensure that we do not allow a treatment modality to usurp our understanding and management of neoplastic disease.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

 
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