Adjuvant Therapy

For patients undergoing radical prostatectomy, if the margins are positive, the follow-up options include radiation therapy or observation. Although there is no high-level evidence to recommend adjuvant radiation therapy at this time, if a patient undergoes aradical prostatectomy and microscopically positive margins are found radiation therapy can reasonably follow after recuperation from surgery. Alternatively, close observation until the development of a detectable PSA is acceptable. If adjuvant radiation therapy is considered, it should be administered prior to the PSA rising above 1.5 ng/mL. Adjuvant antiandrogen therapy is not a standard treatment at this time although in the largest randomized trial to date using the antiandrogen bicalutamide alone at high dose (150 mg) there are indications of a delay in recurrence. No improvement in survival has been demonstrated and longer follow up is needed. If positive lymph nodes are found after radical prostatectomy, either androgen ablation or observation until the PSA becomes detectable is acceptable.In patients for whom the initial intervention is expectant management and who have a life expectancy of less than 10 years, a clinical examination is recommended every 6 to 12 months. Surveillance has been shown to offer 10-year survival rates and quality-adjusted life expectancy similar to radical prostatectomy or radiotherapy. The decision to initiate treatment is driven primarily
by the onset of symptoms. However, patients with high-risk disease may have a better 5-year overall and disease specific survival with active intervention than with observation until symptomatic. For those with a life expectancy of 10 or more years, and who therefore might benefit from definitive local therapy, appropriate surveillance includes a PSA determination and DRE every 6 months, along with a repeat prostate biopsy approximately 1 year after the original diagnosis. Repeat biopsy is recommended to determine whether higher-grade elements are evolving, which may influence prognosis and, hence, the decision to continue observation or proceed to definitive local therapy. Following the initial recommended repeat biopsy, subsequent biopsies may be performed at the observing physician's discretion. As previously discussed, studies remain in progress to identify appropriate trigger points after choosing deferred treatment when interventions with curative intent may still be reliably successful. For those patients initially treated with intent to cure, the serum PSA level should be measured every 6 months for the first 5 years and then rechecked annually. For recurrence after radical prostatectomy, Pound et al. found that 45% of patients recurred within the first two years, 77% within the first five years and 96% by nine years. Because local recurrence may result in substantial morbidity and can, in rare cases, occur in the absence of a PSA elevation, an annual DRE is also appropriate to monitor for prostate cancer recurrence as well as for colorectal disease. Similarly, after radiation therapy, the monitoring of serum PSA level is recommended every 6 months for the first 5 years and then rechecked annually. A digital rectal exam is recommended at least annually.Bone scans are appropriate when patients develop symptoms orwhen the PSA level is increasing rapidly. In one study, the probability of a positive bone scan for a patient not on androgendeprivationtherapy after radical prostatectomy was < 5% unless the PSA increased to 40-45ng/mL. Therefore, particularly in the androgen-dependent state, periodic bone scans as part of routine surveillance do not contribute significantly to the tests outlined above and subsequently are not recommended.

Salvage Work-up and Primary Salvage Therapy

Post-Surgery Patients

Patients who have undergone a radical prostatectomy and experience a biochemical recurrence fall into two groups: those whose PSA level fails to fall to undetectable levels after surgery and those with a persistently elevated or rising PSA level (based on twolaboratory determinations). For those whose PSA level does not fall to undetectable levels with evidence of persistent local tumor, treatment options include radiation therapy (preferred) with or without androgen ablation, or androgen ablation alone. If there is no evidence of persistent local tumor, patients with low risk of metastasis whose surgical margins are positive and seminal vesicles negative, radiotherapy to attempt to eradicate local residual disease is recommended and preferred. Less preferred options were androgen ablation alone or observation. Patients with detectable postoperative PSA levels, negative margins, and positive seminal vesicles are at high risk of disseminated disease and therefore observation or androgen ablation is recommended. Radiotherapy was not endorsed for this group.Patients who develop an undetectable PSA that becomes >0.3ng/mL and rising on two or more determinations may be candidates for further local therapy. A work-up may include a bone scan, a transrectal anastamotic biopsy, and a CT or MRI scan. Currently available Prostascint scans (Cytogen Corporation, Princeton NJ) may be considered but are not generally recommended at this time.If the tests are negative for distant or nodal disease, radiation therapy with or without androgen ablation (preferred), observation, or androgen ablation alone is acceptable. Patients with a rising PSA value more than 24 months after prostatectomy, a PSA doubling time of < 10 months, and a Gleason score of less than 8 with no involvement of the seminal vesicles are more likely to have local rather than distant disease failure and therefore salvage radiation therapy is encouraged. Due to the lack of curative therapy, the unpredictable course of advanced prostate cancer in some patients, and the morbidity of some treatments, androgen ablation (preferred), or observation remains an alternative for patients in this category with metastatic disease or positive lymph nodes.