Prostate Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage III Prostate Cancer Treatment
Hormonal manipulations (orchiectomy or luteinizing hormone-releasing hormone [LH-RH] agonist)
Hormonal manipulations (orchiectomy or LH-RH agonists) may be used in the treatment of stage III prostate cancer.[Level of evidence: 1iiA]
Antiandrogen monotherapy has also been evaluated in men with locally advanced prostate cancer as an alternative to castration.
Evidence (orchiectomy vs. LH-RH agonist):
- In a randomized equivalence study involving 480 men with locally advanced (T3 and T4) disease, those who were treated with castration had a median OS of 70 months, whereas those treated with bicalutamide (150 mg/day) had a median OS of 63.5 months (HR,1.05; 95% CI, 0.81–1.36); these results failed to meet the prespecified criteria for equivalence.[Level of evidence: 1iiA]
Immediate versus deferred hormonal therapy
In patients who are not candidates for or who are unwilling to undergo radical prostatectomy or radiation therapy, immediate hormonal therapy has been compared with deferred treatment (i.e., watchful waiting or active surveillance with hormonal therapy at progression).
Evidence (immediate vs. deferred hormonal therapy):
- A randomized trial looked at immediate hormonal treatment (orchiectomy or LH-RH analog) versus deferred treatment in men with locally advanced or asymptomatic metastatic prostate cancer.[Level of evidence: 1iiA]
- Initial results showed better OS and prostate cancer-specific survival with the immediate treatment. This subsequently lost statistical significance as was recorded in abstract form.
- The incidence of pathologic fractures, spinal cord compression, and ureteric obstruction were also lower in the immediate treatment arm.
- In another trial, 197 men with stage III or stage IV prostate cancer were randomly assigned to receive bilateral orchiectomy at diagnosis or at the time of symptomatic progression (or at the time of new metastases that were deemed likely to cause symptoms).[Level of evidence: 1iiA]
- No statistically significant difference in OS was seen over a 12-year period of follow-up.
- In the EORTC-30891 trial, 985 patients newly diagnosed with prostate cancer, stage T0–4, N0–2, M0, and a median age of 73 years were randomly assigned to receive androgen deprivation, either immediately or on symptomatic disease progression. The study was designed to demonstrate the noninferiority of deferred treatment as compared with immediate treatment in relation to OS.[Level of evidence: 1iiA]
- At a median follow-up of 7.8 years, approximately 50% of the patients in the deferred treatment group had initiated androgen deprivation.
- The median OS in the immediate treatment group was 7.4 years, and, in the deferred treatment group, it was 6.5 years, corresponding to a mortality HR of 1.25 (95% CI, 1.05–1.48), which failed to meet the criteria for noninferiority.
Intermittent versus continuous androgen suppression
When used as the primary therapy for patients with stage III or stage IV prostate cancer, androgen suppression with hormonal therapy is usually given continuously until there is disease progression. Some investigators have proposed intermittent androgen suppression as a strategy to attain maximal tumor cytoreduction followed by a period without therapy to allow tumor repopulation by hormone-sensitive cells. Theoretically, this strategy might provide tumor hormone responsiveness for a longer period of time. An animal model suggested that intermittent androgen deprivation (IAD) could prolong the duration of androgen dependence of hormone-sensitive tumors.