Current uro-oncologic thinking is moving towards the addition of early adjuvant therapy In patients with intermediate and high risk PCa. Several factors may contribute to risk, and different studies have defined risk differently, but a pattern emerges: how much cancer is present, is it localized to the prostate, how aggressive are the cells, is there spread to the lymph nodes, is there distant spread?

Low risk: Stage A or B and Gleason grade 6 or less, and PSA 10 or less.

Intermediate risk: Stage A or B, and Gleason grade 7 or PSA 10 to 20

        Gleason (4+3)=7 is a higher risk factor than (3+4)=7 as is or any Gleason grade 5 cancer in the gland.

High risk: Stage A or B and Gleason grade 7 and PSA greater than 10; or Stage A or B and Gleason grade 8 or higher; or Stage C or D,

Primary therapy: Treatment of the cancer in the prostate by surgery, external beam radiation or brachytherapy, (seeds), or cryotherapy.

Hormonal therapy: Treatment to reduce testosterone levels, (which act as "fertilizer" to PCa), by removal of the testicles; use of drugs that block production, (Zolodex/Lupron,etc.); or by drugs that block the action of testosterone, (Casodex/Nilandrone/Eulixin).

Combined Androgen Blockade (CAB): Combination of testosterone reducers and blockers.

Chemotherapy: Use of non-hormonally active drugs against the cancer.

Neoadjuvant therapy: Hormonal or other drug treatment started before primary therapy, and usually continued for a limited period of time.

   Studies have now begun to show that intermediate risk patients may do significantly better, as a group, when long term, (3 years +), adjuvant hormonal therapy is added to their treatment. This is a significant change in treatment philosophy. The patient should participate in the decision as the side effects are not insignificant.

   There are also strong data suggesting much more aggressive early therapy for high risk PCa. In the past many of these patients were not treated aggressively early. Studies now suggest aggressive early treatment with neoadjuvant therapy prior to radiation or surgery, primary therapy by surgery or combined external radiation, and brachytherapy, or cryotherapy, and long term CAB or other regimens will improve long term survival or disease free intervals for many. There are many ongoing research protocols to improve results.

   Recurrent PCa after primary therapy poses many challenges. Evaluation of rising PSA levels may require bone scans, CT/MRI studies, repeat biopsies, or prostascint scans to evaluate the site of recurrence. Hormonal therapy is usually instituted, When recurrence is localized to the prostate bed, secondary treatments such as radiation after surgery, or cryotherapy or salvage prostatectomy after radiation, may be used in addition to hormonal therapy, in hope of achieving a secondary cure.

   Some prostate cancers become resistant to hormonal therapy, (HRPC), again presenting treatment challenges. Secondary hormonal manipulation with cycling of anti-androgens, or addition of ketoconazole or estrogens, (DES), may help. Various chemotherapy regimens using mitoxantrone and prednisone, or taxotere may be effective. Many other protocols with other drugs, including thalidomide are in progress.