The relationship between HRD score based on GSS algorithm and clinicopathological characteristics, genomic mutations and prognosis in patients with high-risk and metastatic hormone-sensitive prostate cancer / 现代泌尿外科杂志

【Objective】 To statistically analyze the relationship between homologous recombination repair deficiency (HRD) score and clinicopathological characteristics, genomic mutations in patients with high-risk and metastatic hormone-sensitive prostate cancer (mHSPC) and the prognostic predictive value in mHSPC. 【Methods】 A total of 127 patients diagnosed with high-risk prostate cancer and mHSPC, treated at the Department of Urology of Chinese PLA General Hospital during Dec.2021 and Nov.2023 were enrolled.Homologous recombination repair (HRR) gene sequencing was performed, and the genomic scar score (GSS) algorithm were conducted to calculate the HRD score.The relationship between HRD scores and clinicopathological features, genomic alterations, and prognosis were analyzed. 【Results】 The median HRD score was 1.6(0.8, 5.2), 30(23.6%) patients’ HRD scores ≥10, and 11(8.7%) patients’ HRD scores ≥20.Clinicopathological features, including ISUP classification ≥4 (P=0.044) and metastatic status (P=0.008) were associated with high HRD score.Patients with mutations in the BRCA, TP53 and MYC systems had significantly higher HRD score than those with wild-type genes (P<0.05).In mHSPC, the risk of biochemical recurrence was 12.836 times higher in patients with HRD score ≥20 than in those with <20 [OR:12.836 (1.332-124.623), P=0.028]. 【Conclusion】 Baseline HRD score was lower in patients with high-risk prostate cancer and mHSPC.Patients with high HRD score may have higher histological grading (ISUP≥4) and later clinical stage.Further investigation is needed to determine the threshold of HRD scores as biochemical markers suggestive of a poor prognosis.

Effects of radical resection or brachytherapy as initial treatment on the prognosis of patients with high-risk prostate cancer / 现代泌尿外科杂志

【Objective】 To investigate the effects of radical prostatectomy (RP) or brachytherapy (BT) on the prognosis of patients with high-risk prostate cancer as initial treatment, in order to provide a reference for the selection of clinical treatment options. 【Methods】 The clinical data of 133 191 patients diagnosed with high-risk prostate cancer and treated with RP or BT during 2005 and 2014 were extracted from the SEER database.The 5-year and 10- year cancer-specific survival (CSS) and overall survival (OS) were compared with K-M analysis and univariate and multivariate Cox regression.The clinical data of another 253 patients diagnosed with high-risk prostate cancer in Subei People’s Hospital during 2015 and 2020 were collected, including 153 patients who received RP and 100 patients who received BT.The 5-year biochemical progress-free survival (bPFS) and CSS were compared with K-M analysis. 【Results】 Univariate analysis of SEER data showed that BT was associated with a higher risk of death (HR=1.319, 95%CI: 1.256-1.386, P<0.001); age, marital status and TNM stage were associated with higher risk of death (P<0.001).Multivariate analysis, adjusted for relevant variables, showed that BT did not result in a higher risk of death compared with RP (HR=0.964, 95%CI:0.924-0.996, P=0.808). The OS curve showed that the longer the observed survival time, the better OS of RP as compared to BT (P<0.001); however, the CSS survival curve showed that the longer the observed survival time, the better CSS of BT compared to RP (P<0.001).The single-center data analysis showed no significant difference between BT and RP in the 5-year bPFS (P=0.263) and CSS (P=0.946). 【Conclusion】 For patients with high-risk prostate cancer, there is a significant difference in the prognosis of the two treatments if there is no adjustment of age, marital status, TNM stage and other factors, and the efficacy of RP is better than that of BT, especially in patients with survival more than 10 years.However, there is no statistically significant difference in the prognosis after the possible confounding factors are adjusted.Therefore, the initial treatment choice for these patients should be weighed from multiple perspectives, and patients’ choices must be respected after they are fully informed.

Adjuvant versus early Salvage radiation therapy for prostate cancer with adverse pathological features on radical prostatectomy—Do we finally have an answer?

Background: The presence of adverse pathological features like extraprostatic extension, seminal vesicle involvement, or positive margins at radical prostatectomy incurs a high risk of postoperative recurrence. Currently, adjuvant radiotherapy (ART) is the standard of care in these patients, while early salvage radiotherapy (eSRT) is a potential alternative strategy. Aims: The purpose of this paper is to review the latest evidence comparing outcomes of adjuvant versus early SRT in this clinical scenario. Materials and Methods: A systematic review of Google Scholar, PubMed/Medline, and EMBASE was done to identify relevant studies published in the English language, regarding outcomes of adjuvant radiotherapy and early SRT in post radical prostatectomy patients. Twelve studies, including six randomized trials, four retrospective studies, one systematic review, and one metanalysis were included in the final analysis. Results: We found that initial randomized trials demonstrated better event?free survival with adjuvant radiotherapy when compared to observation alone. However, ART was associated with increased risk of overtreatment and thus increased radiation?related toxicity rates. Conclusion: Preliminary evidence from recently reported RCTs suggests that eSRT may provide equivalent oncological outcomes to ART in prostate cancer patients with adverse pathology on radical prostatectomy while decreasing unnecessary treatment and radiation?related toxicity in a significant proportion of patients. However, the final verdict would be delivered after the long?term metastasis?free survival and overall survival outcomes are available.

Outcome of radical prostatectomy as primary treatment for high‑risk prostate cancer patients.

CONTEXT: Recently, there has been considerable interest in the role of radical prostatectomy (RP) in men with high‑risk prostate cancer. AIMS: The objective of our study is to report the outcome of upfront RP in our patients with high‑risk prostate cancer (Stage ≥ cT2c, a pre‑operative serum prostate specific antigen >20 ng/ml or a biopsy Gleason score [GS] 8‑10). SUBJECTS AND METHODS: From 1996 to 2010, 208 patients of prostate cancer (high risk category D’Amico’s criteria) underwent open RP with bilateral pelvic lymphadenectomy. STATISTICAL ANALYSIS USED: The data was statistically analyzed using Kaplan Meier method and log rank test to calculate progression free, metastasis free survival (MFS) and cancer specific survival (CSS). Furthermore multivariate analysis (MVA) was carried out using SPSS 14 software. (IBM company). RESULTS: At 7 and 10 years, prostate cancer‑specific survival (PCSS) was found to be 79.7% and 65%, respectively, biochemical recurrence free survival (BRFS) was 42.4% and 36.7%, respectively and the MFS was 71.1% and 64.4% respectively. High GS was highly predictable of PCSS, BRFS and MFS. Node positivity was the single poor risk factor on MVA whereas biopsy GS, pStage (P = 0.016) and seminal vesicle invasion (P = 0.045) had statistical significance in predicting the MFS. CONCLUSIONS: RP provides accurate pathologic staging of patients with high risk prostate cancer, allows better stratification of patients for further adjuvant therapy and either as an initial approach or part of a multimodal regimen, can provide durable local control and provides excellent CSS.

Efficacy of extra-peritoneal laparoscopic radical prostatectomy in the treatment of high-risk prostate cancer / 中华泌尿外科杂志

Objective To investigate the efficacy and feasibility of extra-peritoneal larparoscopic radical prostatectomy (eLRP) in the treatment of patients with high-risk prostate cancer (HRPC).Methods From February 2009 to December 2013,121 patients,who were diagnosed as HRPC according to the D'Amico definition,were received eLRP.The mean age was 70 years old (range 54 ～ 82 years old).The mean PSA level was 25.45 (range 2.40 ～ 111.31) μg/L and mean Gleason score was 8 (range 6 ～ 10).The classification of clinic stage in this study included 52 cases in cT1-cT2b,58 cases in cT2c,8 cases in cT3a,and 3 cases incT3b,respectively.The perioperative data were collected,including operative time,blood loss,intraoperative complications,urine leakage,lymph leakage,incontinent ability,erectile function and changing of PSA level.Results All the operations were successfully performed.The mean operative time was 165 minutes (range 105 ～341min),the average blood loss was 150 ml(range 50 ～ 1500ml).The intraoperative complications included hemorrhage in 4 cases and intra-operative obturator nerve injury in 3 cases.The mean duration of intestinal function recovery was 35h (range 24 ～72h) The mean interval of catheter indwelling was 9 days (range 7 ～14 days).The anastomotic leakage was found in 12 cases,including 1 day after surgery in 5 cases,2 days after surgery in 3 cases,3 days after surgery in 2 cases,4 day after surgery in 1 case and 5 day after surgery in 1 case.The anastomotic stricture in 3 cases within 2 to 4 months after operation,which the symptom improved after urethral dilation in 2 cases and urethrotomy in 1 case.Deep vein thrombosis was noticed in 1 case 5 days after the procedure.And lymphatic fistula was recorded in 1 case after the operation.Positive surgical margin,seminal vesicle invasion,and positive iliac vessel lymph node were found in 18,21,and 9 patients,respectively.The mean hospitalization duration was 10 days (range 5 ～ 22 d).Of the 107 patients followed-up,Ninety-six patients were continent in 1 year,except other 11 patients.Nerve sparing procedure was performed in 51 patients,and thirty-three of them were potent.The mean PSA level was 0.14 μg/L (range 0 ～8.75 μg/L) six weeks after the surgey.Fourty-eight patients had biochemical recurrence with 5 ～36 months followed-up,mean 18 months.Conclusions Extraperitoneal LRP is an efficacious approach for patients with high-risk prostate cancer.

Comparison study of intensity modulated arc therapy using single or multiple arcs to intensity modulated radiation therapy for high-risk prostate cancer

PURPOSE: Intensity modulated arc therapy (IMAT) is a form of intensity modulated radiation therapy (IMRT) that delivers dose in single or multiple arcs. We compared IMRT plans versus single-arc field (1ARC) and multi-arc fields (3ARC) IMAT plans in high-risk prostate cancer. MATERIALS AND METHODS: Sixteen patients were studied. Prostate (PTVP), right pelvic (PTVRtLN) and left pelvic lymph nodes (PTVLtLN), and organs at risk were contoured. PTVP, PTVRtLN, and PTVLtLN received 50.40 Gy followed by a boost to PTVB of 28.80 Gy. Three plans were per patient generated: IMRT, 1ARC, and 3ARC. We recorded the dose to the PTV, the mean dose (DMEAN) to the organs at risk, and volume covered by the 50% isodose. Efficiency was evaluated by monitor units (MU) and beam on time (BOT). Conformity index (CI), Paddick gradient index, and homogeneity index (HI) were also calculated. RESULTS: Average Radiation Therapy Oncology Group CI was 1.17, 1.20, and 1.15 for IMRT, 1ARC, and 3ARC, respectively. The plans' HI were within 1% of each other. The DMEAN of bladder was within 2% of each other. The rectum DMEAN in IMRT plans was 10% lower dose than the arc plans (p < 0.0001). The GI of the 3ARC was superior to IMRT by 27.4% (p = 0.006). The average MU was highest in the IMRT plans (1686) versus 1ARC (575) versus 3ARC (1079). The average BOT was 6 minutes for IMRT compared to 1.3 and 2.9 for 1ARC and 3ARC IMAT (p < 0.05). CONCLUSION: For high-risk prostate cancer, IMAT may offer a favorable dose gradient profile, conformity, MU and BOT compared to IMRT.