The end of watchful waiting?

Early-stage, localized (clinical stage T1 or T2) prostate cancer has been managed with “watchful waiting”, radiation therapy, or surgery plus or minus adjuvant hormonal therapy. The end of watchful waiting may soon be at hand.

Each of the above treatment modalities has potential adverse consequences. For example, surgical removal of the prostate gland can result in erectile dysfunction and urinary incontinence Accordingly, men newly diagnosed with early-stage prostate cancer and their physicians have faced difficult treatment decisions and have wondered if the outcome justified the treatment, given the slow growing nature of prostate cancer in many cases, particularly in septuagenarians and octogenarians with the disease.

But a recently published study in the New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1011967) shows that radical prostatectomy in men under 65 with early-stage prostate cancer is significantly more effective than watchful waiting. The Scandinavian Prostate Cancer Group Study (SPCG-4) in Sweden, Finland, and Iceland compared outcomes of 695 patients <75 years of age with newly-diagnosed early-stage prostate cancer randomized to treatment by either watchful waiting (n = 348) or radical prostatectomy (n = 347).

Cumulative incidence of death from prostate cancer at 15 years was 14.6% for patients treated with radical prostatectomy and 20.7% for patients managed by watchful waiting.

The study also demonstrated that adjuvant local or systemic treatment of patients with extracapsular growth of prostate cancer may result in improved outcomes.

Importantly, radical prostatectomy provided significantly longer overall survival, longer prostate cancer-specific survival, and lower risk of distant metastases in men who were <65 years of age at the time of diagnosis. At 15 years after radical prostatectomy, men who were enrolled at <65 years of age with prostate cancer experienced an approximate 50% reduction in the endpoints of overall mortality, prostate cancer death, and distant metastases.

Following radical prostatectomy, men <65 with low-risk prostate cancer experienced a reduction in death by any cause, a reduction in prostate cancer death, and a decrease in distant metastases. The findings on men initially diagnosed with low-risk prostate cancer at all ages in the study suggest that some of these tumors, if not surgically removed, may progress.

In contrast, men at least 65 years of age who were diagnosed with any risk level of early-stage prostate cancer and treated with radical prostatectomy demonstrated no significant benefits in overall survival, prostate-specific survival, or reduction in distant metastases. The lack of clarity in effects of treatments in the older patients, however, may be due to lack of statistical power in the study and/or competing causes of death.

Based on the long-term data from SPCG-4, watchful waiting is no longer an option for men under 65 with early-stage prostate cancer. An aggressive approach involving surgery is recommended for these younger men. In older men with early stage prostate cancer, however, the watch-and-wait approach still can be considered as an option, at least until relative benefits of treatment modalities for the older population of patients are clarified.