Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Stage IV prostate cancer is defined by the American Joint Committee on Cancer's TNM classification system:
If you just learned that you or a loved one has advanced prostate cancer, you may have many questions and concerns. By taking the time to research your condition, you've taken a good first step. Here are answers to the most common questions. After looking over these answers, click on other articles in this guide to find in-depth information about treatments, side effects, and other issues that affect you and your family.
T4, N0, M0, any prostate-specific antigen (PSA), any Gleason.
Any T, N1, M0, any PSA, any Gleason.
Any T, any N, M1, any PSA, any Gleason.
Extraprostatic invasion with microscopic bladder neck invasion (T4) is included with T3a.
Treatment selection depends on age, coexisting medical illnesses, symptoms, and the presence of distant metastases (most often bone) or regional lymph node involvement only. The most common symptoms originate from the urinary tract or from bone metastases. Palliation of symptoms from the urinary tract with transurethral resection of the prostate (TURP) or radiation therapy and palliation of symptoms from bone metastases with radiation therapy or hormonal therapy are an important part of the management of these patients. Bisphosphonates are also under clinical evaluation for the management of bone metastases.
The Agency for Health Care Policy and Research (AHCPR) (now the Agency for Healthcare Research and Quality) performed a systematic review of the available randomized clinical trial evidence comparing radiation therapy with radiation therapy and prolonged androgen suppression performed by its Technology Evaluation Center, an evidence-based Practice Center of the Blue Cross and Blue Shield Association.[Level of evidence: 1iiA] Some patients with bulky T2b tumors were included in the studied groups. The meta-analysis found a difference in 5-year overall survival (OS) in favor of radiation therapy plus continued androgen suppression using a luteinizing hormone-releasing hormone (LHRH) agonist or orchiectomy, compared with radiation therapy alone (hazard ratio [HR] = 0.631; 95% confidence interval [CI], 0.479-0.831). This reduction in overall mortality indicates that adjuvant androgen suppression should be initiated at the time of radiation therapy and continued for several years. The optimal duration of therapy and the issue of utility of neoadjuvant hormonal therapy have not been determined.
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]
In a small randomized trial of 98 men who underwent radical prostatectomy plus pelvic lymphadenectomy and were found to have nodal metastases (stage T1-2 N1, M0), immediate continuous hormonal therapy with the LHRH agonist goserelin or with orchiectomy was compared with deferred therapy until documentation of disease progression.[Level of evidence: 1iA]; After a median follow-up of 11.9 years, both OS and prostate cancer-specific survival were superior in the immediate adjuvant therapy arm (P = .04 and P = .004, respectively). At 10 years, the survival rate in the immediate therapy arm was about 80% versus about 60% for the deferred therapy arm. Another trial (RTOG-8531), with twice as many patients in a randomization, showed no difference in OS with early versus late hormonal manipulation.