“No Turning Bax” in the Combined Battle against Prostate Cancer:

Abstract

Prostate cancer is the most commonly diagnosed cancer in men in the United States with more than 218,000 cases detected each year (2). Although widespread serum prostate-specific antigen (PSA) screening has enabled detection of the disease at earlier stages (3–6), prostate cancer still accounts for more than 27,000 deaths each year (2). Radiation therapy or surgery is the standard treatment and is effective for most, but not all (7, 8). Men who have locally advanced prostate cancer at diagnosis, defined as stage T2c-4 but with PSA <150 ng/mL, are particularly at risk for treatment failure (9). Consequently, this is a subset of patients for whom hormonal manipulation is often combined with radiation therapy to try to achieve the best chance of cure. Hormonal ablation is most commonly achieved by administering an antiandrogen (e.g., flutamide) and a gonadotropin (e.g., goserelin), which together achieve androgen deprivation and apoptosis of the cancer cells. This strategy is not without cost, as androgen deprivation is associated with erectile dysfunction, osteopenia (10, 11), and hot flashes (12), as well as potentially increased risk of diabetes (13, 14) and hypertension (15, 16). Accurately predicting which patients require that the radiation therapy be supplemented by long-term androgen deprivation or may avoid treatment without such side effects would be of great help (17). RTOG Protocol 92-02 was a clinical trial that attempted to help define the optimal duration of androgen deprivation when combined with radiation therapy (18, 19). Patients with stage T2c-4 prostate cancer and PSA <150 were given androgen ablation 2 months before and for 2 months during radiation therapy for a total of 4 months of androgen ablation. Patients were then randomly assigned to either the group that received no additional androgen deprivation (short-term AD-RT arm) or 24 months of androgen deprivation (long-term AD-RT). The LTAD-RT arm showed improved disease-free survival, an improvement that was particularly marked in patients with histologically aggressive disease (i.e., those with Gleason score of 8–10). RTOG 92-02 has therefore influenced the current standard of care for treating high-grade prostate cancer, which now consists of androgen deprivation in conjunction with radiation therapy for treating prostate cancer of high grade, stage, or PSA.