External-beam radiation therapy (EBRT) with or without hormonal therapy

The Blue Cross and Blue Shield Association Technology Evaluation Center, an evidence-based practice center of the Agency for Healthcare Research and Quality (AHRQ), performed a systematic review of the available randomized clinical trial evidence comparing radiation therapy with radiation therapy and prolonged androgen suppression.[40][Level of evidence A1] Some patients with bulky T2b tumors were included in the studied groups.

The Blue Cross and Blue Shield Association Technology Evaluation Center, an evidence-based practice center of the Agency for Healthcare Research and Quality (AHRQ), performed a systematic review of the available randomized clinical trial evidence comparing radiation therapy with radiation therapy and prolonged androgen suppression.[40][Level of evidence A1] Some patients with bulky T2b tumors were included in the studied groups.

The meta-analysis found a difference in 5-year OS in favor of radiation therapy plus continued androgen suppression using an LH-RH agonist or orchiectomy compared with radiation therapy alone (HR, 0.63; 95% CI, 0.48–0.83).

In a randomized, prospective clinical trial, 18 months of androgen suppression with an LH-RH agonist appears to have provided results that were similar to 36 months with respect to OS and disease-specific survival.[55][Level of evidence A1] In the trial, 630 men with stage II to stage IVA cancer (clinical stage T3–T4, or PSA >20 ng/ml, or Gleason score >7) received 70 Gy of radiation in 35 fractions alone plus a total of either 18 or 36 months of goserelin acetate.

In a randomized, prospective clinical trial, 18 months of androgen suppression with an LH-RH agonist appears to have provided results that were similar to 36 months with respect to OS and disease-specific survival.[55][Level of evidence A1] In the trial, 630 men with stage II to stage IVA cancer (clinical stage T3–T4, or PSA >20 ng/ml, or Gleason score >7) received 70 Gy of radiation in 35 fractions alone plus a total of either 18 or 36 months of goserelin acetate.

With a median follow-up of 9.4 years, OS was nearly identical in each study arm (62% at 10 years; HRdeath, 1.02; 95% CI, 0.81–1.29, P = .8), as was prostate cancer–specific survival (HRprostate death, 0.95; 95% CI, 0.58–1.55, P = .8).

In a randomized, prospective clinical trial, 18 months of androgen suppression with an LH-RH agonist appears to have provided results that were similar to 36 months with respect to OS and disease-specific survival.[55][Level of evidence A1] In the trial, 630 men with stage II to stage IVA cancer (clinical stage T3–T4, or PSA >20 ng/ml, or Gleason score >7) received 70 Gy of radiation in 35 fractions alone plus a total of either 18 or 36 months of goserelin acetate.

Global quality of life was nearly identical on both study arms, but sexual activity and interest in sex was moderately better in the 18-month arm.[55][Level of evidence A3]

The optimal duration of neoadjuvant hormonal therapy has been studied. In a randomized trial (TROG 96.01 [ACTRN12607000237482]) of 818 men with locally advanced (T2b, T2c, T3, and T4), nonmetastatic cancer treated with radiation therapy (i.e., 66 Gy in 2 Gy daily fractions to the prostate and seminal vesicles but not including regional nodes). Patients were randomly assigned to radiation therapy alone, 3 months of neoadjuvant androgen deprivation therapy (NADT) (goserelin 3.6 mg SQ each month plus flutamide 250 mg PO tid) for 2 months before and during radiation, or 6 months of NADT for 5 months before and during radiation.[54][Level of evidence A1]

The optimal duration of neoadjuvant hormonal therapy has been studied. In a randomized trial (TROG 96.01 [ACTRN12607000237482]) of 818 men with locally advanced (T2b, T2c, T3, and T4), nonmetastatic cancer treated with radiation therapy (i.e., 66 Gy in 2 Gy daily fractions to the prostate and seminal vesicles but not including regional nodes). Patients were randomly assigned to radiation therapy alone, 3 months of neoadjuvant androgen deprivation therapy (NADT) (goserelin 3.6 mg SQ each month plus flutamide 250 mg PO tid) for 2 months before and during radiation, or 6 months of NADT for 5 months before and during radiation.[54][Level of evidence A1]

After a median follow-up of 10.6 years, there were no statistically significant differences between the radiation alone group and the radiation plus 3 months of NADT group.

The optimal duration of neoadjuvant hormonal therapy has been studied. In a randomized trial (TROG 96.01 [ACTRN12607000237482]) of 818 men with locally advanced (T2b, T2c, T3, and T4), nonmetastatic cancer treated with radiation therapy (i.e., 66 Gy in 2 Gy daily fractions to the prostate and seminal vesicles but not including regional nodes). Patients were randomly assigned to radiation therapy alone, 3 months of neoadjuvant androgen deprivation therapy (NADT) (goserelin 3.6 mg SQ each month plus flutamide 250 mg PO tid) for 2 months before and during radiation, or 6 months of NADT for 5 months before and during radiation.[54][Level of evidence A1]

However, the 6-month NADT arm showed better prostate cancer-specific mortality and overall mortality than radiation alone; 10-year all-cause mortality 29.2% versus 42.5% (HR, 0.63; 95% CI, 0.48–0.83, P = .0008).

The duration of neoadjuvant hormonal therapy was tested in another trial (RTOG-9910 [NCT00005044]) of 1,489 eligible men with intermediate-risk prostate cancer (T1b–4, Gleason score 2–6, and PSA >10 but ≤100 ng/mL; T1b–4, Gleason score 7, and PSA <20; or T1b–1c, Gleason score 8–10, and PSA <20) and no evidence of metastases. The men were randomly assigned to receive short-course neoadjuvant–androgen suppression (an LH-RH agonist plus bicalutamide or flutamide for 8 weeks before and 8 weeks during radiation therapy) or long-course neoadjuvant-androgen suppression (28 weeks before and 8 weeks during radiation therapy). Both groups received 70.2 Gy radiation in 39 daily fractions to the prostate and 46.8 Gy to the iliac lymph nodes.[56][Level of evidence A1]

The duration of neoadjuvant hormonal therapy was tested in another trial (RTOG-9910 [NCT00005044]) of 1,489 eligible men with intermediate-risk prostate cancer (T1b–4, Gleason score 2–6, and PSA >10 but ≤100 ng/mL; T1b–4, Gleason score 7, and PSA <20; or T1b–1c, Gleason score 8–10, and PSA <20) and no evidence of metastases. The men were randomly assigned to receive short-course neoadjuvant–androgen suppression (an LH-RH agonist plus bicalutamide or flutamide for 8 weeks before and 8 weeks during radiation therapy) or long-course neoadjuvant-androgen suppression (28 weeks before and 8 weeks during radiation therapy). Both groups received 70.2 Gy radiation in 39 daily fractions to the prostate and 46.8 Gy to the iliac lymph nodes.[56][Level of evidence A1]

After a median of 9.4 years, 10-year prostate specific mortality, the primary end point, was low in both study arms: 5% versus 4% (HR, 0.81; 95% CI, 0.48–1.39).[56][Level of evidence A1]

The duration of neoadjuvant hormonal therapy was tested in another trial (RTOG-9910 [NCT00005044]) of 1,489 eligible men with intermediate-risk prostate cancer (T1b–4, Gleason score 2–6, and PSA >10 but ≤100 ng/mL; T1b–4, Gleason score 7, and PSA <20; or T1b–1c, Gleason score 8–10, and PSA <20) and no evidence of metastases. The men were randomly assigned to receive short-course neoadjuvant–androgen suppression (an LH-RH agonist plus bicalutamide or flutamide for 8 weeks before and 8 weeks during radiation therapy) or long-course neoadjuvant-androgen suppression (28 weeks before and 8 weeks during radiation therapy). Both groups received 70.2 Gy radiation in 39 daily fractions to the prostate and 46.8 Gy to the iliac lymph nodes.[56][Level of evidence A1]

No statistically significant differences in overall mortality or in locoregional disease progression were found.[56][Level of evidence A1]

The duration of neoadjuvant hormonal therapy was tested in another trial (RTOG-9910 [NCT00005044]) of 1,489 eligible men with intermediate-risk prostate cancer (T1b–4, Gleason score 2–6, and PSA >10 but ≤100 ng/mL; T1b–4, Gleason score 7, and PSA <20; or T1b–1c, Gleason score 8–10, and PSA <20) and no evidence of metastases. The men were randomly assigned to receive short-course neoadjuvant–androgen suppression (an LH-RH agonist plus bicalutamide or flutamide for 8 weeks before and 8 weeks during radiation therapy) or long-course neoadjuvant-androgen suppression (28 weeks before and 8 weeks during radiation therapy). Both groups received 70.2 Gy radiation in 39 daily fractions to the prostate and 46.8 Gy to the iliac lymph nodes.[56][Level of evidence A1]

There was also no apparent differential effect of androgen suppression duration among any of the risk-group subsets.