High-dose radiation employing external beam radiotherapy and high-dose rate brachytherapy with and without neoadjuvant androgen deprivation for prostate cancer patients with intermediate- and high-risk features

Abstract

The role of neoadjuvant androgen deprivation (NAD) in high-risk prostate cancer patients receiving high-dose radiotherapy (RT) remains unstudied. To evaluate the effect of a course of NAD, we reviewed the experiences of three institutions treating these patients with combined RT and high-dose rate brachytherapy (HDR). Of 1260 prostate cancer patients with high-risk features (pretreatment prostate-specific antigen (PSA) X10, Gleason Score (GS) X7, or T stage XT2b), 560 received no NAD (n ¼ 308) or NAD for p6 months (n ¼ 252). Median dose to the prostate from RT and HDR was 42 and 23 Gy, respectively. Average total biologic equivalent prostate dose was 4100 Gy (a/b ¼ 1.2). Median follow-up was 4.3 years. Pretreatment characteristics were similar on v 2 tables for all 560 patients treated with or without NAD including pretreatment PSA (P ¼ 0.11), GS (P ¼ 0.4), and clinical T stage (P ¼ 0.2). Outcomes worsened for patients receiving NAD (5-year distant metastasis (DM) 10 vs 5% (P ¼ 0.04); cause-specific survival (CSS), 93 vs 98% (P ¼ 0.005)).Higher 5-year DM rates and lower CSS occurred in NAD patients with a GS between 8 and 10 (n ¼ 112 (P ¼ 0.03, P ¼ 0.02)), pretreatment PSAX15 (n ¼ 136 (P ¼ 0.03, P ¼ 0.008)), and palpable disease XT2a (n ¼ 434 (P ¼ 0.04, P ¼ 0.02)). The only two significant risk factors for DM on Cox multivariate analysis were GS (P ¼ 0.003, HR 2.8) and NAD (P ¼ 0.03, HR 2.7). AD given before definitive high-dose RT did not benefit prostate cancer patients with intermediate-and high-risk features. We favor the use of concurrent/adjuvant AD over prolonged NAD for prostate cancer patients for whom AD is clinically indicated.

Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

“…The median number of patients accrued per institution was 8 (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and the average was 9 patients. The average monthly accrual for the study was 5.9 patients.…”

“…There have been multiple updates of their results. (8,(14)(15)(16)(17)(18) They have continued to dose escalate using increasingly larger fractions of HDR treatment ranging from 5.5-6.5 Gy × 3 to 8.25-11.5 Gy × 2 combined with 46 Gy of external beam radiotherapy. The most recent update showed the treatment is well tolerated with favorable biochemical outcomes.…”

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer

“…8,[13][14][15]19 It was our choice to treat the boost before EBRT for the following reasons; first at the start of SBRT, patients were naive from acute toxicities linked to EBRT; second at the start of the EBRT, prostate cancer cells were exposed at high radiation dose (BED2 109.25 Gy). Up to date, there is no larger studies on HDR-like prostate cancer treatment.…”

“…[4][5][6][7] Until now, hypofractionation with high dose rate has been utilized by high dose rate brachytherapy (HDR-BRT), establishing itself as a viable and safe approach as monotherapy or boost after EBRT. [8][9][10][11][12][13][14][15] The HDR-BRT has the advantage of better accuracy to the dose delivered and avoidance of complications secondary to organ movement compared to EBRT. In intermediate-and high-risk disease, HDR-BRT alone may not deliver adequate dose to periprostatic tissues.…”

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

“…There were too few high-risk patients treated without ADT (n = 2) to do a meaningful comparison of outcomes without vs. with ADT (Figure-2). Vargas et al (27) observed worse DMFS, prostate-cancer specific survival, and OS in patients with a Gleason score 8-10, palpable disease, and a PSA ≥15 ng/mL who received ADT. It is possible that patients who received ADT may have had a history of congestive heart failure or myocardial infarction, accounting for the poor outcomes with ADT in that report (28).…”