RESUMO
OBJECTIVE: To assess the long-term safety of nerve-sparing radical prostatectomy (NSRP) in men with high-risk prostate cancer (PCa) by comparing survival outcomes, disease recurrence, the need for additional therapy, and perioperative outcomes of patients undergoing NSRP to those having non-NSRP. PATIENTS AND METHODS: We included consecutive patients at a single, academic centre who underwent open RP for high-risk PCa, defined as preoperative prostate-specific antigen level of > 20 ng/mL and/or postoperative International Society of Urological Pathology Grade Group 4 or 5 (i.e., Gleason score ≥ 8) and/or ≥pT3 and/or pN1 assessing the RP and lymph node specimen. We calculated a propensity score and used inverse probability of treatment weighting to match baseline characteristics of patients with high-risk PCa who underwent NSRP vs non-NSRP. We analysed oncological outcome as time-to-event and calculated hazard ratios (HRs). RESULTS: A total of 726 patients were included in this analysis of which 84% (n = 609) underwent NSRP. There was no evidence for the positive surgical margin rate being different between the NSRP and non-NSRP groups (47% vs 49%, P = 0.64). Likewise, there was no evidence for the need for postoperative radiotherapy being different in men who underwent NSRP from those who underwent non-NSRP (HR 0.78, 95% confidence interval [CI] 0.53-1.15). NSRP did not impact the risk of any recurrence (HR 0.99, 95% CI 0.73-1.34, P = 0.09) and there was no evidence for survival being different in men who underwent NSRP to those who underwent non-NSRP (HR 0.65, 95% CI 0.39-1.08). There was also no evidence for the cancer-specific survival (HR 0.56, 95% CI 0.29-1.11) or progression-free survival (HR 0.99, 95% CI 0.73-1.34) being different between the groups. CONCLUSION: In patients with high-risk PCa, NSRP can be attempted without compromising long-term oncological outcomes provided a comprehensive assessment of objective (e.g., T Stage) and subjective (e.g., intraoperative appraisal of tissue planes) criteria are conducted.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Recidiva Local de Neoplasia/patologia , Prostatectomia/efeitos adversos , Estudos Longitudinais , Gradação de TumoresRESUMO
Many human cancers manifest the capability to circumvent attack by the adaptive immune system. In this work, we identified a component of immune evasion that involves frequent up-regulation of fragile X mental retardation protein (FMRP) in solid tumors. FMRP represses immune attack, as revealed by cancer cells engineered to lack its expression. FMRP-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, FMRP's immunosuppression was multifactorial, involving repression of the chemoattractant C-C motif chemokine ligand 7 (CCL7) concomitant with up-regulation of three immunomodulators-interleukin-33 (IL-33), tumor-secreted protein S (PROS1), and extracellular vesicles. Gene signatures associate FMRP's cancer network with poor prognosis and response to therapy in cancer patients. Collectively, FMRP is implicated as a regulator that orchestrates a multifaceted barrier to antitumor immune responses.