Following radical treatment of localized prostate cancer, up to 30% of patients may relapse. At relapse, PET/CT using PSMA, Choline or Fluciclovine plays a major role in defining the site of relapse and therefore could modify radiotherapy prescription in terms of indication, dose or volume. We will discuss the role of PET/CT-guided radiotherapy as a salvage treatment in different clinical situations: prostate bed relapse, pelvic lymph node relapse, distant metastases and relapse in a previously irradiated region.
Following prostatectomy, salvage prostate bed radiotherapy is advocated if the PSA rises above 0.2 ng/ml, and ideally below 0.5 ng/ml. In approximately 50% of cases, PSMA PET/CT can determine the site of relapse, frequently within the prostate bed. Is there a role for radiotherapy-dose intensification in macroscopic prostate bed relapse? As shown in the SAKK 09/10 trial, increasing the total dose to the prostate bed up to 70 Gy increases toxicity rates but does not improve biochemical relapse-free survival. However, retrospective series suggest that boosting the dose to the macroscopic nodule could improve biochemical control without increasing toxicity. Another intensification strategy is to combine salvage radiotherapy and radiosensitizing drugs such as novel androgen-receptor targeting agents. Ongoing trials will help determine the best strategy of radiotherapy in macroscopic prostate bed relapses.
Other frequent sites of relapse following radical treatment are pelvic lymph nodes. High dose radiotherapy targeting oligoreccurent pelvic lymph nodes, using SBRT or elective pelvic nodal irradiation may increase tumor control at the cost of limited toxicity. The Oligopelvis GETUG P12 trial is a randomized phase 3 trial that compares 6-months Androgen –Depriving Therapy (ADT) alone to ADT + elective pelvic radiotherapy. The STORM PEACE 5 trial will determine if a boost dose to the PET/CT defined lymph nodes can increase tumor control. Early toxicity results of the STORM PEACE 5 trial did not show any increased toxicity and efficacy results are eagerly awaited.
Prostate cancer may also relapse distantly to non-pelvic lymph nodes, bones or less frequently to visceral sites. Randomized phase 2 trials such as SABR-Comet, Oriole or Stomp, showed that SBRT targeting oligorecurrent metastases could delay the introduction of systemic treatments and increase progression-free survival. Several randomized phase 3 studies are ongoing, in order to prove that adding metastases-targeted SBRT to systemic treatment can improve survival.
The rather recent advent of PET-CT tracers lead also to the discovery of local relapses within previously irradiated areas, such as the prostate or the prostate bed. In order to delay the need for a systemic treatment for these local relapses, salvage local therapies (surgery, cryotherapy, HIFU…) have been developed. More recently salvage reirradiation using brachytherapy or SBRT was shown to be feasible despite manageable toxicity, in small series of patients. Ongoing phase I/II trials will help determine the best radiotherapy strategies in theses clinical situation (dose, fractionation) and should provide prospective evidence of efficacy.
To conclude, the development of novel PET/CT radiotracers completely changed staging of prostate cancer. However, the potential benefits of novel PET/CT radiotracers to improve the efficacy of radiotherapy remain to be determined in prospective randomized phase 3 trials.