Stage III Prostate Cancer Treatment
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.
Evidence (intermittent vs. continuous androgen suppression):
- A systematic review of all five randomized trials addressing this issue found no reliable data on the relative effectiveness of intermittent versus continuous androgen suppression on OS, prostate cancer-specific survival, disease progression, or quality of life.[Level of evidence: 1iiA]
- All five trials were small and had short follow-up. Intermittent therapy remains under evaluation.
- In a subsequent randomized trial, 626 men with clinically advanced prostate cancer (T3–T4, M0–M1, PSA ≥4) that responded to an initial 3-month induction course of cyproterone acetate plus an LH-RH analog were randomly assigned to either continue the regimen or cease treatment until there was evidence of progression.[Level of evidence: 1iiA]
- After 100 months of follow-up (median 51 months), there was no difference in OS (HR, 0.99; 95% CI, 0.80–1.23; P = .84) for continuous androgen deprivation versus IAD.
- Quality of life between the two treatment strategies was similar, but IAD was associated with lower rates of hot flashes and gynecomastia.
- Replication of these findings is important, and there are ongoing trials such as SWOG-9346 to address this further.
Radical prostatectomy with or without EBRT
Radical prostatectomy may be used with or without EBRT (in highly selected patients). Because about 40% to 50% of men with clinically organ-confined disease are found to have pathologic extension beyond the prostate capsule or surgical margins, the role of postprostatectomy adjuvant radiation therapy has been studied.
Evidence (radical prostatectomy with or without EBRT):
- In a randomized trial of 425 men with pathologic T3, N0, M0 disease, postsurgical EBRT (60–64 Gy to the prostatic fossa over 30–32 fractions) was compared with observation.[38,39]
- After a median follow-up of about 12.5 years, OS was better in the radiation therapy arm; HRdeath of 0.72 (95% CI, 0.55–0.96; P = .023). The 10-year estimated survival rates were 74% and 66% in the radiation therapy and control arms, respectively.
- The 10-year estimated metastasis-free survivals were 73% and 65% (P = .016).[Level of evidence: 1iiA]
- Short-term complication rates were substantially higher in the radiation therapy group: overall complications were 23.8% versus 11.9%, rectal complications were 3.3% versus 0%, and urethral stricture was 17.8% versus 9.5%.
- The role of preoperative (neoadjuvant) hormonal therapy is not established.[40,41] Also, the morphologic changes induced by neoadjuvant androgen ablation may even complicate assessment of surgical margins and capsular involvement.