Clinical results of EBRT

2.4.1. Clinical results of conventional EBRT

The results of several large single-institution comparison between radical prostatectomy (RP) and EBRT were reported.

Investigators from Cleveland Clinic Foundation, USA analyzed 1,682 patients with clinical stage T1 and T2 disease treated with either RP or RT. They reported that the 8-year biochemical relapse free survival (bRFS) rates for RP and conventional EBRT less than 72 Gy were 72% and 34%, respectively, and conventional EBRT less than 72 Gy was inferior to RP in the 8-year bRFS rate (Fig 1)[6].

Figure 1. Biochemical relapse-free survival by treatment modality: RT to doses < 72 Gy, RT to doses > or = 72 Gy, and RP for all (A), favorable (B), and unfavorable patients(C).

(Cited from Kupelian PA et al.[5])

Figure 1. Biochemical relapse-free survival by treatment modality: RT to doses < 72 Gy, RT to doses > or = 72 Gy, and RP for all (A), favorable (B), and unfavorable patients(C).

D'Amico et al. reported a retrospective cohort study of 2635 patients with either RP or RT of median dose to 70.4 Gy (95% CI, 69.3-70.4 Gy) [7]. Eight-year bRFS rates for low-risk (T1c, T2a, PSA < or = 10 ng/ml, and Gleason score (GS) < or = 6) patients were 88% and 78% for RP and RT, respectively. Eight-year bRFS rates for intermediate-risk (T2b or GS 7 or PSA > 10 and < or = 20 ng/ml) patients with < 34% positive prostate biopsies were 79% and 65% for PR and RT, respectively. Eight-year bRFS rates were 36% versus 35% for intermediate-risk patients with at least 34% positive prostate biopsies and 33% versus 40% for high-risk (T2c or PSA > 20ng/ml or GS > or = 8) patients treated with RP versus those treated with RT, respectively. In conclusion, in their retrospective cohort study, intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. For the meanwhile, Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of bRFS that were not found to be significantly different.

2.4.2. Clinical results of 3D-CRT

Above-mentioned investigators from Cleveland Clinic Foundation reported that 3D-CRT more than 72 Gy was superior to Conventional EBRT less than 72 Gy and very similar to RP in the 8-year bRFS (6). Eight-year bRFS rate were 86% versus 86% (p = 0.16) for favorable-risk (T1 to T2a, GS < or = 6, PSA < or = 10 ng/ml) patients and 62% versus 61% (p = 0.96) for unfavorable-risk (T2b to T2c, GS > or = 7, PSA > 10 ng/ml) patients with RP versus those treated with RT > or = 72 Gy (Fig 1). Several study also have demonstrated that doses in excess of 70 to 72 Gy are associated with a reduction in the risk of recurrence compared with lower doses [8-12].

2.4.3. Clinical results of IMRT

Investigators from Memorial Sloan Kettering Cancer Center (MSKCC) reported their experience in 1002 patients treated with IMRT of 86.4 Gy [13]. They reported 7-year bRFS rates for low, intermediate, and unfavorable risk group patients as 98.8%, 85.6%, and 67.9%, respectively. In this report, they concluded that high dose IMRT to 86.4 Gy for localized prostate cancer resulted in excellent clinical outcomes with acceptable toxicity.

2.4.4. Clinical results of combined with Androgen Deprivation Therapy (ADT) and EBRT

Thus far, there have been five phase III randomized controlled trials for high-risk prostate cancer that compared radiotherapy alone with radiotherapy and ADT [14-18]. In all of these trials, ADT improved bRFS. In three of these four trials, ADT improved both overall survival (OS) and cause-specific survival (CSS).

From above-mentioned results, combining ADT with radiotherapy should be recommended in the high-risk group.

For intermediate-risk prostate cancer, two studies were published. Investigators from Brigham and Women's Hospital reported their randomized trial that consisted of 206 patients [19]. Two months each of total androgen blockade given before, during, and after radiotherapy for a total of 6 months. After a median follow-up of 4.52 years, ADT had improved 5-year bRFS, CSS, and OS. The Trans-Tasman Radiation Oncology Group (TROG) 96.01 study consisted of 802 patients, who were randomized to radiotherapy alone, 3 months, or 6 months of neoadjuvant hormones with radiotherapy. Five-year bRFS was significantly improved in the 3-month and 6-month arms as compared to the control arm. Although the 6-months arm showed significantly improved 5-year CSS, the 3-month arm was not significantly improved.

The thing to note is that these trials used doses less than 72 Gy that would be considered suboptimal by today's standard. Whether the benefit of ADT remains in the current era of dose escalation is currently unclear.

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