Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?

Abstract

Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy

“…However, between 27% and 53% of all patients undergoing RP or RT develop PSA recurrence [1]. Approximately 30% (20-40%) of patients following RP and 30-50% of males treated with RT will experience BCR within 10 years post-therapy [2]. For several years, PSA has been used for detection of recurrent and progressive disease after primary treatments.…”

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

“…However, the optimal ADT duration is still debated when associated with salvage RT. Interpretation of the RTOG-9601 and GETUG-16 results remains obscure; none of these trials being exclusively on the early intervention of post-operative RT with PSA < 0.5 ng/mL [61]. Other factors considered, including pre-existing comorbidities, particularly cardiometabolic disease, and the applicability of radiation dose escalation, may improve estimation of the optimum time period of ADT in combination with RT for locally advanced PCa.…”

“…Analysis of the quality of life of men receiving cancer treatments may help recognize the intermediate-and long-term effects of such treatments on them. Apalutamide is also tested in the randomized phase III CARLHA 2 GETUG 33 trial (NCT04181203), and also in the two-arm phase II NRG GU006 study (NCT03371719) [61]. In a similar approach, DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801) is exploring the addition of 96 weeks of Darolutamide to RT and ADT, either for primary definitive therapy or in an adjuvant setting for very high-risk PCa (NCT04136353), and RTOG 3506 (STEEL) is studying the addition of 2 years of Enzalutamide with salvage RT and 2 years of ADT when aggressive features are displayed (NCT03809000) [61,68].…”

Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules

“…In the definitive treatment setting, there is robust evidence of the superiority of hypofractionation over standard fractionation in the improvement of disease control [19,20], whereas in the postoperative setting hypofractionation remains a debated issue [21].…”

“…Nevertheless, to date, this treatment approach in the salvage setting must be considered solely investigational [21].…”