Recurrent Prostate Cancer Treatment
Likewise, after radiation therapy with curative intent, persistently elevated or rising PSA may be a prognostic factor for clinical disease recurrence. However, reported case series have used a variety of definitions of PSA failure. Criteria have been developed by the American Society for Therapeutic Radiology and Oncology Consensus Panel.[11,12] The implication of the various definitions of PSA failure for overall survival (OS) is not known, and as in the surgical series, many biochemical relapses (rising PSA alone) may not be clinically manifested in patients treated with radiation therapy.[13,14]
Hormonal Therapy for Recurring Disease
Intermittent versus continuous androgen suppression therapy
The majority of men who are treated for recurrence after initial local therapy are asymptomatic, and the recurrence is detected by a rising PSA. It is possible that intermittent androgen deprivation therapy (IAD) can be used as an alternative to continuous androgen deprivation (CAD) therapy (ADT) in an attempt to improve quality of life and decrease the amount of time during which the patient experiences the side effects of hormonal therapy, without decreasing the survival rate.
- This important clinical question was addressed in a "noninferiority" designed, randomized, controlled trial with 1,386 men who had rising PSA levels (>3 ng/ml, with serum testosterone >5 nmol/L) more than 1 year after primary or salvage radiation therapy for localized prostate cancer.[Levels of evidence: 1iiA, 1iiB, 1iiC]
- The ADT arm consisted of 8-month treatment cycles with an LH-RH agonist (combined with a nonsteroidal antiandrogen for at least the first 4 weeks) that was reinstituted if the PSA level exceeded 10 ng/ml. The study was powered to detect (with 95% confidence) an 8% lower OS rate in the IAD group compared with the CAD group at 7 years.
- After a median follow-up of 6.9 years (maximum follow-up 11.2 years), OS in the two groups was nearly identical, and the study was stopped (median survival 8.8 vs. 9.1 years; hazard ratio [HR]death of 1.02; 95% confidence interval [CI], 0.86–1.21). This fulfilled the prospective criterion of noninferiority.
- In a retrospective analysis, prostate cancer-specific mortality was also similar in the two arms (HR, 1.18; 95% CI, 0.90–1.55; P = 0.24). In addition, IAD was statistically significantly better than CAD in several quality-of-life domains, such as hot flashes, desire for sexual activity, and urinary symptoms. Patients on the IAD study arm received a median of 15.4 months of treatment versus 43.9 months on the CAD arm.
- The study does not address the unanswered question about whether the initiation of any ADT for an elevated PSA after initial local therapy extends survival compared with delay until clinically symptomatic progression. Of note, 59% of all deaths were unrelated to prostate cancer, and only 14% of all patients died of prostate cancer.