EBRT.[3,4,25,26,27] Hormonal therapy (LHRH agonist or orchiectomy) should be considered in addition to EBRT.[5,5,6,9,12,14,16,28,29] Although the RTOG-9413 trial showed an increased progression-free survival at 4 years for patients with a 15% estimated risk of lymph node involvement who received whole-pelvic radiation therapy as compared with prostate-only radiation therapy, OS and PSA failure rates were not significantly different.[30,31][Level of evidence: 1iiDiii] Definitive radiation therapy should be delayed until 4 to 6 weeks after transurethral resection to reduce incidence of stricture. Radiation therapy designed to decrease exposure of normal tissues using methods such as computed tomography (CT)-based 3-D conformal treatment planning is under clinical evaluation.
In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b-T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of an LHRH-agonist plus long-term flutamide (250 mg orally three times per day) with or without EBRT. Nineteen percent of the men had tumor stage T2 and 78% had T3. At 10 years, both overall mortality (29.6% vs. 39.4%; 95% CI for the difference, 0.8%-8.8%) and the prostate cancer-specific mortality (11.9% vs. 23.9%; 95% CI for the difference, 4.9%-19.1%) favored combined hormonal and radiation therapy.[Level of evidence: 1iiA]
While flutamide might not be considered a standard hormonal monotherapy in the setting of T2 or T3, nonetheless, it is interesting to see that radiation therapy provided a DFS or tumor-specific survival advantage even though this monotherapy was applied. This analysis rests on the assumption that flutamide does not shorten life expectancy and cancer-specific survival. Radiation therapy was not delivered by current standards of dose and technique.
Hormonal manipulations (orchiectomy or LHRH agonist).[Level of evidence: 1iiA]
Radical prostatectomy, with or without pelvic lymphadenectomy (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. In a randomized trial of 425 men with pathologic T3, N0, M0 disease, postsurgical EBRT (60 Gy-64 Gy to the prosthetic fossa over 30-32 fractions) was compared to observation.[36,37] After a median follow-up of about 12.5 years, OS was better in the radiation therapy arm; hazard ratio of death equaled 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%, respectively. The role of preoperative (neoadjuvant) hormonal therapy is not established.[38,39] Also, the morphologic changes induced by neoadjuvant androgen ablation may even complicate assessment of surgical margins and capsular involvement.
Careful observation without further immediate treatment.[41,42]