Analysis Of Influencing Factors Related To Urinary Control Recovery And Positive Surgical Margin After Radical Prostatectomy

【Background】Prostate cancer（PCa）is the second most frequent malignancy and the fifth leading cause of cancer-related mortality among men globally.The current best option considered for an early localized PCa is surgery intervention,but post-operative urinary incontinence has plagued the postsurgical rehabilitation of patients,thus the protection of urinary control in clinical practice has received considerable attention.However,the protection of urinary control during operation is associated with a high incidence of positive surgical margins（PSM,presence of tumor cells at the inked margin of resection）after the procedure.Therefore,the balance between the protection of urinary control and PSM has been perplexing urologists and impacting on the quality of life of the patients.Studies on improving urinary control and reducing the rate of PSM have been performed,but have not yet obtained unified conclusion.With the continuous improvement of individualized diagnosis and precision surgery,as well as the advanced and mature implementation of robot-assisted laparoscopic surgery and targeted radionuclide imaging in the field of surgery,Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography(⁶⁸Ga-PSMA PET/CT)examinations are increasingly used by urologists for robot pre-surgical evaluation of robot surgery and ultimately for the complete excision of the tumor.However,the efficacy of preoperative ⁶⁸Ga-PSMA PET/CT in reducing the rate of PSM after robot-assisted laparoscopic radical prostatectomy,especially in high-risk PCa,still needs to be investigated.【Objectives】1.Exploring the risk and protective factors affecting the recovery of urinary control after radical prostatectomy in patients with PCa by combining with clinical practice.2.Analyzing the risk and protective factors affecting PSM after radical prostatectomy in PCa.3.Investigating the impact of ⁶⁸Ga-PSMA PET/CT scan performed before robot-assisted laparoscopic radical prostatectomy on postoperative PSM in PCa patients.【Methods】1.Retrospective analysis of clinical and follow-up data of 319 patients undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy in the department of urology at three centers（Xijing Hospital,Baoji people’s Hospital,and Yuncheng Central Hospital）was performed.Univariate Cox regression analysis was conducted,and the variables with clinical and statistical significance were included in a multivariate Cox regression analysis.Then backward elimination method（P=0.05）was used to determine the risk factors for recovery of urinary control after radical prostatectomy.2.Retrospective analysis of clinical and follow-up data of 319 patients undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy in the department of urology at three centers（Xijing Hospital,Baoji people’s Hospital,and Yuncheng Central Hospital）was conducted.Univariate logistic regression analysis was performed and the variables with clinical and statistical significance were included in multivariate logistic regression model.Then backward elimination method（P=0.05）was used to analyze the risk factors affecting PSM after radical prostatectomy.3.Retrospective analysis of clinical data from 118 patients with high-risk PCa undergoing robot-assisted laparoscopic radical prostatectomy at Xijing Hospital of Air Force Military Medical University between June 2019 and December 2020.Of these,47 patients underwent ⁶⁸Ga-PSMA PET/CT scan preoperatively and 71 patients did not receive⁶⁸Ga-PSMA PET/CT scan.The two groups were compared with the postoperative pathological stage,operation times,postoperative hospital stay,postoperative Gleason score,intraoperative blood loss,and the rate of PSM.The measurement data did not match normal distribution and were represented as M(P₂₅and P₇₅),and the comparison between groups was estimated using the Mann-Whitney U test.The counting data were described in terms of proportions or percentages,and the differences between groups were compared using theX²test.The difference was considered statistically significant（P<0.05）.【Results】1.A total of 282 patients who met the inclusion and exclusion criteria were eventually included in the analysis.The median recovery time of patients with urinary control after radical prostatectomy was 5 months（range:4-9）.The results of univariate Cox regression analysis demonstrated that age,preoperative prostate-specific antigen（PSA）,history of transurethral resection of the prostate（TURP）,postoperative Gleason score,PSM,surgical approach,operation times,preservation of neurovascular bundle during operation,and regular anal exercise were associated with the recovery of postoperative urinary control.Multivariate Cox regression analysis identified that preoperative total PSA（t PSA）>20ng/m L was the risk factor（hazard ratio[HR]=0.557,95%confidence interval[CI]:0.407-0.761）for the recovery of postoperative urinary control in PCa patients.Intraoperative neurovascular bundle preservation（HR=2.850,95%CI:1.999-4.065）,intraoperative bladder neck preservation（HR=1.687,95%CI:1.199-2.373）,and postoperative regular anal exercise（HR=5.134,95%CI:3.755-7.019）were protective factors for recovery of postoperative urinary control in patients with PCa.2.Of the 319 patients included,136（42.63%）had PSM and 183（57.37%）had negative surgical margins（NSM）.Univariate logistic analysis revealed that the elevated preoperative t PSA,preoperative endocrine therapy,history of TURP,postoperative Gleason score,clinical T stage,bladder neck preservation,and neurovascular bundle during the operation were associated with the postoperative PSM.The results of multivariate logistic regression analysis predicted that clinical stage T3（odds ratio[OR]=2.764,95%CI:1.584-4.821）,clinical stage T4（OR=7.864,95%CI:1.430-43.252）,preoperative t PSA>20 ng/m L（OR=3.889,95%CI:2.065-7.325）,and preoperative Gleason score≥8（OR=2.289,95%CI:1.312-3.993）achieved risk factors for postoperative PSM.Neoadjuvant androgen deprivation therapy（ADT;OR=0.311,95%CI:0.165-0.585）was a protective factor for PSM after the operation.3.The study group(the patients underwent ⁶⁸Ga-PSMA PET/CT scan preoperatively)was associated with shorter operation time compared to the control group[175（155-205）vs.205（155-235）mins,P=0.003],and the rate of PSM in the study group was significantly lower than that in the control group（23.40%[11/47]vs.45.07%[32/71],P=0.017）.For patients with t PSA value of>20.0 ng/m L,the rate of PSM in the study group was lower than that in the control group[30.56%（11/36）vs.58.5%（24/41）,P=0.014];for patients with pathological stage≥p T3,the rate of PSM decreased in the study group compared with the control group[8/26（30.77%）vs.23/37（62.16%）,P=0.014];for patients with Gleason score≥8,the study group was associated with lower PSM rate compared to the control group[27.59%（8/29）vs.61.11%（22/36）,P=0.007].In the study group,11 cases had positive lymph nodes in before the operation by PSMA PET,10（90.91%）cases had postoperative pathology positive,and 1 case with negative lymph nodes by PSMA PET showed postoperative pathology positive.Lymph node dissection was performed in 26cases in the control group and identified 16 cases（61.54%）with pathologically positive after the operation.【Conclusions】1.The elevated preoperative t PSA（especially t PSA>20 ng/m L）was identified as risk factor,while intraoperative neurovascular bundle preservation,intraoperative bladder neck preservation,and regular postoperative anal exercise were protective factors for recovery of postoperative urinary control in PCa.A critical time window for recovery of urinary control after radical prostatectomy was six months.2.The results demonstrated that the elevated preoperative clinical T stage,preoperative t PSA（especially preoperative t PSA>20 ng/m L）,and preoperative Gleason score（≥8）were risk factors for postoperative PSM,while preoperative ADT was a protective factor for postoperative PSM.Higher postoperative PSM rates were associated with higher preoperative t PSA,higher pathological stage,and higher preoperative Gleason scores.Preoperative neoadjuvant ADT can effectively reduce the PSM rate after the operation.3.Preoperative ⁶⁸Ga-PSMA PET/CT examination in patients with high-risk PCa guides the surgeons to optimize the operational setup,accurate removal of PCa,and decrease PSM rates after the operation,ultimately maximizing the benefit for the patients.For PCa patients with high risk factors（t PSA>20 ng/m L,Gleason score≥8,clinical stage≥T3）,preoperative ⁶⁸Ga-PSMA PET/CT examination can aid surgeons in accurately removing cancer focus during surgery and reducing postoperative PSM rates.Meanwhile,preoperative ⁶⁸Ga-PSMA PET/CT examination enhances the efficiency of lymph node dissection in PCa patients with lymph node metastasis,and eventually provides substantial benefits for patients.