SRT in Combination With Pembrolizumab in Patients With Recurrent Prostate Cancer After Radical Prostatectomy

Current guidelines recommend a salvage radiation therapy (SRT) with at least 66 Gy as preferred treatment option in patients with biochemical recurrence (BCR) resp. PSA (prostate-specific antigen) persistence after radical prostatectomy (RP). The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. The optimal timing for a radiation therapy cannot be clearly defined by the available literature. A radiation therapy as early as possible with a PSA level \<0,5 ng/ml seems to be beneficial. The guideline recommendation is based on two non-randomized controlled trials that showed an improved cancer-specific survival and a better local tumor control. A complete biochemical response is to be expected in approx. 60-70% of patients after 12 months. The established imaging modality in patients with BCR used to be computed tomography of the abdomen and bone scintigraphy for the detection of skeletal lesions. The introduction of PSMA PET/CT (prostate-specific membrane antigen positron emission tomography combined with CT) has changed the imaging in patients with recurrent prostate cancer and several studies could show improved oncological results compared to patients undergoing standard treatment without positron emission tomography (PET) positive lesions with a 10% improvement in biochemical recurrence-free survival after 2 years. Immunotherapy alone has not yet proven to be efficacious in prostate cancer as a monotherapy in smaller studies. Several trials could show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating genitourinary malignancies, whereas more studies are needed to uncover the exact underlying mechanism. In brief, radiation therapy of the location of recurrence increases the tumor´s immunogenic potential and a systemic immunological reaction is initiated that leads to an increased activity of the immune system against tumor tissue (abscopal effect). Lately several trials have been evaluating a possible synergistic effect with tolerable side-effects. A trial combining those two treatment regimens in the early treatment of prostate cancer recurrence is not available up to date. The clinical benefit of concomitant androgen deprivation therapy (ADT) is controversial and literature failed to show a clear overall survival benefit for all patients. Several retrospective trials have been evaluating a concomitant ADT and for patients with risk factors like suspicious lymph-nodes in staging diagnostics. Several studies have been evaluating the effect of concomitant ADT though. Shipley et al. could show the addition of 24 months of bicalutamide to SRT resulted in significantly higher rates of long-term overall survival. However, sub-group analyses revealed that this effect counts mainly for patients with PSA of \>0.7 ng/ml before SRT. The GETUG-AFU trial did not find any survival benefit for short term (6 months) ADT additionally to SRT. However, a significant benefit in progression-free survival after 120 months of follow-up time was reported. A combination therapy of pembrolizumab and radiation therapy has not been evaluated before in this patient population. The investigators hypothesize that this combination is more effective than radiation therapy alone due to a radiogenic triggered immunomodulation which increases the anti-tumor effect of pembrolizumab. For patients with BCR or PSA persistence after RP no such treatment regimen has been tested yet.