According to the literature, there is a significant correlation of dose escalation and response to treatment for prostate carcinoma [4, 5, 8, 9]. High dose of conventional fractionated radiation schedules or hypofractionation schemes and associated higher rectal doses have evoked the need for improved protection of the rectum during prostate cancer irradiation [7, 9]. Radiotherapy side effects include rectal irritation and bleeding, erectile dysfunction and urinary frequency. Since in conformal radiotherapy, irradiation isodose distribution includes a part of the rectum, displacing irradiated prostate away from anal and rectum, would reduce damage and therefore side effects.
Levy et al. reported on Prospace as an implantable, biodegradable, inflatable, preshaped triangular balloon of commercially used poly(L-lactide-co-epsilon-caprolactone) co-polymer material to provide separation between prostate and rectum . Biocompatibility and degradability of the Prospace in conjunction with local irradiation were evaluated in several in vivo studies . The device was found to be biocompatible in subcutaneously implanted rabbits up to 42 days, in a transperineally implanted dog, up to 12 months and in 8 transperineally implanted pigs, up to 6 months. Since the balloon has been inflated, it remained stable for several months and subsequently the tissues remained separated. In experimental animals, histopathology has shown no systemic or local toxicity. After three months post irradiation evaluation, in pigs that received 15 Gy (3 fractions once per week) the investigators documented the stability of the balloon position without any local or systemic side effects. They also reported that the balloon's preparation ensures no bonding across anatomical interfaces by means of mechanical stability during implantation. In our case the non-rigid registration techniques with sequential CT scans of the pelvis showed also stability of the device . Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated [3–9]. However, there was some indication that genitourinary toxicity was worse for patients treated with dose escalated IMRT techniques, although most studies did not find a significant treatment effect . In our study the GI toxicity was minimal and equivalent to IMRT techniques, while the GU toxicity was slightly worse in accordance with the reported urinary toxicity from IMRT trials. However we have to emphasize that the technique used was conventional 3D conformal and not IMRT, by means of the sparing of the rectum only due to distance achieved from the irradiated area and definitely of the inability of bladder sparing. Although IMRT is the standard technique for prostate irradiation in many RT departments, the balloon implementation would offer a safe dose escalation, in terms of further decreasing mainly the potential rectal toxicity.
Livi L et al. reviewed 100 patients with localized prostate cancer, receiving 80 Gy with a biphasic technique (3DCRT + IMRT) . The median follow-up time was 12 months, while 18% developed acute Grade 2 rectal toxicity, and no patient experienced acute grade 3 or higher rectal symptoms. Acute Grade 2 urinary symptoms were observed in 44% of the patients. Ruy et al. in another trial with 173 patients reported the toxicity on a 3D-CRT trial for prostate carcinoma with a prescription dose of 79.2Gy . The grade III acute toxicity for bladder or bowel was less than 3%, while 54% of patient presented no or grade I toxicity. Michalski in another study, showed remarkably low grade III toxicity (4%), for patients who received 78Gy at the prostatic gland . Ghadjar et al. reported on 102 patients with 80 Gy prescribed dose, delivered with IMRT technique . The study showed 2% grade II GI toxicity and 43% of less than grade III GU toxicity. Mantzinger et al. in EORTC22991 trial with either 3D-CRT or IMRT for intermediate or high risk prostate cancer, reported 0.8% and 6.3% of grade III GI and GU toxicity, respectively . Al-Mamgani et al. reported a significant lower incidence of acute grade II or higher GI toxicity when IMRT was used instead of 3D-CRT (20% vs 61%, respectively), while no significant difference was noted for GU toxicity between the two techniques . Deville et al.  with the use of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon for immobilization, reported maximum GI toxicity of grade 1 and 2 up to 23% and 8%, respectively. In our study the rate of acute toxicity was remarkably low. The reason for this should be the use of Prospace, concerning the GI toxicity and the small field used for the irradiation of the prostatic gland only concerning the GU toxicity (no pelvic fields used). The IIEF−5 questionnaire showed no impact to erectile function related either to Prospace or to radiotherapy, although the position of the balloon was at the anatomical cite of the neurovascular bundle. This fact further indicates the safety of the balloon implementation. However, in our study the number of patients is really low, making the extraction of safe conclusions impossible, even for the evaluation of acute toxicity. Thus we have to emphasize on the implementation method used rather than on the radiation induced morbidity. Moreover, we have to underline the need of a longer follow up, in order to further evaluate the late rectal and urinary radiation induced toxicity.
According to the current literature, PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer . Although in our study the follow-up was short, the PSA nadir was obviously achieved as shown in Table 4, meaning that the response to irradiation was excellent. In any case this should be confirmed with more patients and extended follow-up.
At last but not least, we have the impression that the balloon would be appropriate also for interstitial brachytherapy as monotherapy for the prostate cancer . This would have a potential clinical impact in terms of the potential elimination of the already minimum acute rectal toxicity related to brachytherapy. However, concerning the deviation of US, there must be a correction for the filling of the balloon since the content is water and consequently should be different from the surrounding soft tissues. Moreover, there are publications using HDR brachytherapy as boost after external beam RT, reporting a prescription dose of 40-50Gy for the external beam [41–43]. From our point of view, concerning the brachytherapy boost, our technique would allow the escalation of the dose up to 60Gy for the external beam, but this would need a dosimetric study with more patients.
In conclusion, the Prospace implementation is feasible and the radiation induced toxicity especially for the rectum is minimal, equivalent to IMRT techniques. More patients are needed for the confirmation of the results of the present study, which is on-going.