Recent Advances in Prostate Cancer Treatment

Imaging plays a vital role in detecting the recurrence of prostate cancer (PCa) to guide the choice of salvage therapy. Gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography (⁶⁸Ga-PSMA-11 PET/CT) is useful for detecting PCa recurrence. We assessed the pattern of PCa recurrence stratified by serum prostate-specific antigen level and type of primary local treatment in men with biochemical recurrence (BCR) after primary local therapy with radical prostatectomy or external beam radiotherapy (EBRT) using ⁶⁸Ga-PSMA-11 PET/CT. We reviewed patients imaged with ⁶⁸Ga-PSMA-11 PET/CT for the localization of the site of PCa recurrence. We determined the site and number of lesions due to PCa recurrence at different PSA levels. A total of 247 men (mean age of 65.72 ± 7.51 years and median PSA of 2.70 ng/mL (IQR = 0.78–5.80)) were included. ⁶⁸Ga-PSMA-11 PET/CT detected the site of recurrence in 81.4% of patients with a median number of lesions per patient of 1 (range = 1–5). ⁶⁸Ga-PSMA-11 PET/CT positivity was 43.6%, 75.7%, 83.3%, 90.0%, and 95.8% at PSA levels of <0.5, 0.5–1.0., 1.1–2.0, 2.1–5.0, and 5.0–10.0, respectively. The most common site of recurrence was in the prostate gland/bed at all PSA levels. Pelvic, extra-pelvic, and combined pelvic and extra-pelvic sites of recurrence were seen in 118, 50, and 33 patients, respectively. The risk of extra-pelvic recurrence increases with rising PSA levels. ⁶⁸Ga-PSMA-11 PET/CT has a high lesion detection rate for biochemical recurrence of PCa in patients previously treated with primary local therapy. Full article

Background: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. Methods: Radical prostatectomy (RP) was performed on 108 PCa stage pT2–pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. Results: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = −2.0% d⁻¹ (AUC = 0.85 (95% CI, 0.78–0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 − CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). Conclusion: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period. Full article

Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC. Full article