Intra Operative Single Dose-Radiotherapy (SDRT) in Prostate Cancer
Intra Operative Radiotherapy (IORT) has the capability to increase the radiation dose with very limited or no increase of toxicity as a result of the target exposition during the surgical procedure. For this reason, IORT can be used in various settings of gastro-intestinal, gynecological and genito-urinary tumours aiming at dose intensification and consequently at increasing tumour control rate.
IORT can be delivered using dedicated linear accelerator producing electron beams, X-rays sources delivering low-energy radiation or high dose-rate brachytherapy units through catheters positioned in the tumour bed and loaded with iridium-192. In particular, electrons generated by linacs are used for gastro-intestinal cancers and brachytherapy sources can be conveniently used for IORT procedures in gynecological and genito-urinary tumours.
The rationale for dose escalation with IORT in prostate cancer is based on the demonstration of a dose–response relationship and a low α/β value in the radiobiological linear quadratic model. IORT is considered to significantly reduce the risk of relapse since locally advanced/high-risk prostate cancer is associated with significant risk of relapse when treated with radical prostatectomy alone, the risk being the highest when the margins are positive. IORT has been explored in high-risk prostate cancers in combination with radical prostatectomy and post-operative external beam radiotherapy to improve local control via dose escalation.
The initial study on IORT (SDRT) in prostate cancer came from Japan, where patients with localized tumors were treated through a perineal IORT approach without prostatectomy. Nine patients of 14 patients achieved local control and none of the 14 patients developed any serious complications of the bladder, urethra or rectum. However, the study suggested that single doses of 3300 cGy by IORT alone or 2500 cGy as a boost in conjunction with external radiotherapy can be curative for prostatic cancer with minimal morbidity.
Recently IORT in combination with radical prostatectomy and regional lymph node dissection before or after the surgical procedure was used as a boost dose prior to prostate removal in most cases. When a single-shot radiation strategy was adopted, a dose of 18–21 Gy was delivered.
The diameter and bevel end angle of the applicators were selected based on target dimensions, considering a margin of at least 5 mm around the prostate and the necessity to reach the target underneath the pubic arch while sparing the bladder. The electron beam energy, between 9 and 12 MeV, depended on the depth of the target and the position of the rectum, which should be spared.
Therefore, patient selection seems to be varied in the various studies. In terms of post-surgical early and late side effects, IORT for prostate cancer has resulted as an acceptable procedure. But clinical trials with long follow-up are needed to assess the real efficacy of IORT in locally advanced prostate cancer. Encouraging local control and acceptable toxicity has been demonstrated.
The best candidates for SDRT WITH IORT possibly combined with EBRT, could be the patients staged T3N0 with high risk for positive margins. In the future, multicenter studies should be designed to better clarify the real role of SDRT for dose escalation in locally advanced prostate cancer patients.