Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

“…The probability of lymph node involvement based on the Roach equation [34] was >30% for half of our patients. It is generally considered that whole pelvic irradiation may have potential benefit for these HR patients [35]. In our population, however, potential lymph-node metastasis was controlled by ADT alone, without irradiation.…”

Whole-pelvis Radiotherapy in the Radiation Treatment of Intermediate- and High-risk Prostate Cancer: How to Improve the Therapeutic Ratio of a Potentially Effective but still Unsatisfactory Treatment?

“…Truthfully, the suspicion that the commonly adopted Genitourinary Tumor Group (GETUG) [2] and Radiation Therapy Oncology Group (RTOG) [3] guidelines, limiting the cranial border of WPRT to S1/S2 and L5/S1 interspace, respectively, may lead to a suboptimal coverage of the lymph-nodal area to be prophylactically irradiated, contributing therefore to the lack of a convincing benefit deriving from WPRT, is not new [4]. Accordingly, the ongoing RTOG 0924 trial [5], investigating the benefit of WPRT in addition to high-dose radiotherapy and androgen deprivation therapy (ADT) in the radiation treatment of unfavorable intermediate-risk and favorable high-risk prostate carcinoma, set the upper limit of WPRT at the superior border of L4/L5, in order to adequately include, as suggested by surgical analyses of lymph-nodal drainage [6], also the common iliac and lower para-aortic nodes.…”

“…This is indeed a key point, since it has to be definitively proven that ADT could render a suboptimal radiation dose curative. More importantly, while it is probably true that ADT+radiotherapy is superior to ADT alone [4], the opposite hypothesis, that WPRT alone is less effective than WPRT+ADT, is highly debatable and as yet unproven. The widespread availability of intensity-modulated and imageguided radiation therapy providing more comprehensive coverage of tumor targets while reducing the doses to the healthy surrounding tissues [4] allows the delivery of WPRT doses in the range of 50 Gy to 54 Gy, if not higher, with more than acceptable toxicity [8].…”

“…More importantly, while it is probably true that ADT+radiotherapy is superior to ADT alone [4], the opposite hypothesis, that WPRT alone is less effective than WPRT+ADT, is highly debatable and as yet unproven. The widespread availability of intensity-modulated and imageguided radiation therapy providing more comprehensive coverage of tumor targets while reducing the doses to the healthy surrounding tissues [4] allows the delivery of WPRT doses in the range of 50 Gy to 54 Gy, if not higher, with more than acceptable toxicity [8]. Doses to pelvic nodes higher than those more commonly used at present (45 Gy) could reduce the need for concomitant ADT in intermediate risk patients [9], and could theoretically increase the efficacy of WPRT in the subset of those high-risk patients in whom WPRT has thus far proved to be ineffective [4].…”

“…The time appears ripe for a standardization of WPRT irradiation fields in order to fully encompass not only the obturator, internal and external iliac, and presacral but also the perirectal, common iliac, and lower para-aortic nodes [4]. Equally undelayable is the inclusion, in any future phase 3 trial evaluating the possible benefit of prophylactic WPRT, of an arm investigating WPRT delivered at doses significantly greater than 45 Gy and in the range of 50 Gy to 54 Gy, but without the additional confounding bias of ADT, in order to ultimately assess the real cost/benefit profile of this extremely promising, but thus far unsatisfactory, therapeutic approach.…”