Neoadjuvant Androgen Receptor Signaling Inhibitors before Radical Prostatectomy for Non-Metastatic Advanced Prostate Cancer: A Systematic Review.
Shahrokh F ShariatPawel RajwaFahad QuhalTatsushi KawadaKensuke BekkuEkaterina LaukhtinaMarkus von DeimlingMarcin ChlostaPierre I KarakiewiczTakahiro KimuraShahrokh F ShariatPublished in: Journal of personalized medicine (2023)
(1) Background: Several phase II studies, including randomized controlled trials (RCTs), assessed the efficacy of adding androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) as a neoadjuvant treatment in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Summarizing the early results of these studies could help in designing phase III trials and patient counseling. (2) Methods: We queried three databases in January 2023 for studies that included PCa patients treated with neoadjuvant ARSI-based combination therapy before RP. The outcomes of interest were oncologic outcomes and pathologic responses, such as pathologic complete response (pCR) and minimal residual disease (MRD). (3) Results: Overall, twenty studies (eight RCTs) were included in this systematic review. Compared to ADT or ARSI alone, ARSI + ADT was associated with higher pCR and MRD rates; this effect was less evident when adding a second ARSI or chemotherapy. Nevertheless, ARSI + ADT resulted in relatively low pCR rates (0-13%) with a high proportion of ypT3 (48-90%) in the resected specimen. PTEN loss, ERG positive, or intraductal carcinoma seem to be associated with worse pathologic response. One study that adjusted for the effects of possible confounders reported that neoadjuvant ARSI + ADT improved time to biochemical recurrence and metastasis-free survival compared to RP alone. (4) Conclusions: Neoadjuvant ARSI + ADT combination therapy results in improved pathologic response compared to either alone or none in patients with non-metastatic advanced PCa. Ongoing phase III RCTs with long-term oncologic outcomes, as well as biomarker-guided studies, will clarify the indication, oncologic benefits, and adverse events of ARSI + ADT in patients with clinically and biologically aggressive PCa.
Keyphrases
- radical prostatectomy
- prostate cancer
- locally advanced
- rectal cancer
- combination therapy
- phase iii
- neoadjuvant chemotherapy
- phase ii
- squamous cell carcinoma
- open label
- lymph node
- clinical trial
- free survival
- systematic review
- radiation therapy
- case control
- small cell lung cancer
- randomized controlled trial
- double blind
- placebo controlled
- case report
- minimally invasive
- cell proliferation
- type diabetes
- stem cells
- study protocol
- pi k akt
- robot assisted
- bone marrow
- signaling pathway