An older randomized study comparing radical prostatectomy at diagnosis to expectant therapy (careful observation with therapy as needed) in stage I and stage II cancers did not show a statistically significant difference in survival; however, the trial of 95 patients was not large enough to exclude a small but medically significant difference in OS, nor did it include information to measure time to progression, cancer-specific survival, or quality of life.
Often, baseline rates of PSA changes are thought to be markers of tumor progression. Even though a tumor marker or characteristic may be consistently associated with a high risk of prostate cancer progression or death, it may be a very poor predictor and therefore of very limited utility in making therapeutic decisions. For example, baseline PSA and rate of PSA change were associated with subsequent metastasis or prostate cancer death in a cohort of 267 men with clinically localized prostate cancer who were managed by watchful waiting in the control arm of a randomized trial comparing radical prostatectomy to watchful waiting.[8,9] Nevertheless, the accuracy of classifying men into groups whose cancer remained indolent versus those whose cancer progressed was poor at all examined cut points of PSA or PSA rate of change.
The role of adjuvant hormonal therapy in patients with locally advanced disease has been analyzed by the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality). Most patients have more advanced disease, but patients with bulky T2b to T2c tumors were included in the study groups that were re-evaluating the role of adjuvant hormonal therapy in patients with locally advanced disease. Randomized clinical trial evidence comparing radiation therapy to radiation therapy with prolonged androgen suppression has been published. The meta-analysis found a difference in 5-year OS in favor of radiation therapy plus continued androgen suppression (LHRH agonist or orchiectomy) compared to radiation therapy alone (HR = 0.631; 95% CI, 0.479-0.831).[Level of evidence: 1iiA]
Likewise, a meta-analysis of seven randomized controlled trials comparing early (adjuvant or neoadjuvant) to deferred hormonal treatment (LHRH agonists and/or antiandrogens) in patients with locally advanced prostate cancer, whether treated by prostatectomy, radiation therapy, or watchful waiting, showed improved overall mortality (RR = 0.86; 95% CI, 0.82-0.91).[Level of evidence: 1iiA]
Bicalutamide has not been shown to improve OS in patients with localized or locally advanced prostate cancer. The Early Prostate Cancer (EPC) program is a large, randomized, placebo-controlled, international trial that compared bicalutamide (150 mg orally per day) plus standard care (radical prostatectomy, radiation therapy, or watchful waiting, depending on local custom) with standard care alone for men with nonmetastatic localized or locally advanced prostate cancer (T1-2, N0, NX; T3-4, any N; or any T, N+). Less than 2% of the 8,113 men had known node disease. At a median follow-up of 7.4 years, there was no difference in OS between the bicalutamide and placebo groups (about 76% in both arms [HR = 0.99; 95% CI, 0.91-1.09; P = .89]).[Level of evidence: 1iA]