Clinical Research Of125Cases With Radical Prostatectomy

BackgroundProstate cancer (PCa) is one of the most common malignant tumors in male genitourinary system. The morbidity is relatively high in old male, and it is a big threat against people’s health and life. Radical prostatectomy (RP) is currently the most commonly used therapeutic option for treating localized PCa which is defined as stage cT2or lower with no metastasis in preoperative time for the good results, long time survival, and acceptable incidence of both short-term and long-term complications[1]. In the past, it is not recommended for locally advanced PCa which is defined as stage cT3tumor to undergo RP because of the significantly increased rate of positive margin, unpredictable metastasis of extremital lymph nodes and the distant metastasis. While a few studies showed that RP maybe also benefit to those patients, although it has been still widerspread controversy in recent years[2]. Most scholars believed that RP is not a good choice for stage cT4, metastasis of lymph nodes or distant metastasis PCa for the surgical procedure could only offer better evidence for staging but useless for the treatment[3]. Excitedly, a large-scale study has reported that RP maybe also benefit to the patients with metastasis of lymph nodes which could increase cancer specific survival[4].One of the key points of controlling hemorrhage is the reasonable deal with dorsal vascular complex (DVC) in surgical procedure. Most scholars believed that ligation of DVC could be effectively, while a recent retrospective research shown that ligation-free is also feasible with the development of technology, without increased rate of bleeding or blood transfusion during and after the operation. Moreover, another study showed that selective ligature of the DVC after its section is contribute to early recovery of continence.With the development of medical technology, radical prostatectomy has been a reliable, effective treatment method for PCa. But some problems are worth while pondering and should be improved. First, Surgical treatment of pathological stage T3(or beyond) PCa, or with lymphatic metastasis, has always been a controversial issue, it is necessary and could be helpful for future multi-center meta-analysis to continuously study. Secondly, as a less applied technique, it is urgent to evaluate the safety, feasibility and superiority of DVC ligation free. What’s more, it is necessary to continuously explore the following several questions:first, the relationship between neurovascular bundle (NVB) preservation and its effect on micturition control; second, the correlation between preoperative prostate specific antigen (PSA), postoperative gleason scores and pathological stages;third, the independent predictive factors of biochemical recurrence, and so on.ObjectiveA total of125patients’ preoperative clinical data, perioperative data, intraoperative and postoperative complications, biochemical recurrence-free survival time, time of death and lost to follow-up and outcome were analyzed statistically so as to explore the following several questions:first, the safety, feasibility and superiority of DVC ligation free; second, the relationship between NVB preservation and its effect on micturition control; third, the correlation between PSA, postoperative gleason scores and pathological stages. Survival analyses were made by using the kaplan-meier method to clarify the influence of several different factors on biochemical recurrence-free survival time. Furthermore, to explore the independent predictive factors of biochemical recurrence by using the method of cox regression. By means of a series of above studies, we expect to provide statistical bases for establishing more reasonable operative indications, improving the method, effect of operation and life quality of the patients after operation. What’s more, it could provide single-center research datas for some controversial issues all over the world.MethodsIt was a retrospective series case study. A total of125patients’follow-up information were analyzed statistically. All of the patients underwent radical prostatectomy from february2002to february2013in Zhujiang Hospital, Southern Medical University. The cases diagnosed by pathological result preoperatively and postoperatively, with complete clinical data and a follow-up time more than3months.1Perioperative data collection We collected all the patients’ perioperative datas by means of clinic doctor workstation, Jiahe computer-based patient record system and case record department. These datas include:①the preoperative datas: basic information, first onset symptoms, international prostate symptom score, body mass index, american society of anesthesiologists grade, underlying diseases and accompanying diseases, PSA, fPSA/PSA (%), clinical stage, gleason scores, treatment history, continence, erectile function (just for the patients younger than70years old with satisfactory erectile function);②the intraoperative datas:the date, methods, time, blood loss of operation, volume of blood transfusion, number of pelvic lymph nodes which were dissected, treatments of NVB and DVC, surgical margin and intraoperative complications (include severe emorrhage, heart and lung failure, injury of rectal, bladder, ureter, obturator nerve and so on);③the postoperative datas:gleason score, pathological stage, preserved time of installing catheter, perioperative complications (refers to the postoperative complications which occurred before discharge, include severe hemorrhage, pulmonary infection, heart and lung failure, urinary fistula, intestinal fistula, vesicourethral anastomosis stenosis, urethral stenosis, incontinence, deep vein thrombosis, pulmonary embolism, poor wound healing, lymphocystis and so on), treatments.2Methods of postoperative follow-up datas collection Set up the operation time and postoperative follow-up schedule table for each patient. Follow-up were scheduled every3months in the first2years and every6months in the third to fifth year, and once a year afterwards. Inform the patients who didn’t return back to the hospital on time due to different reasons by telephone dialogues or e-mail. We asked the patients who unable to return back to our hospital to follow-up in the local hospital and send the results to us by means of telephone, text messages, photos, letters, e-mail and so on. Make sure of the integrity and reliability of follow-up datas by effective communication and record them in detail. Regard the patients who lost contact with us or extremely unwilling to cooperate with follow-up to loss of follow-up.3Postoperative follow-up datas These datas include:①follow-up date;②datas within3months after surgery, include:PSA, fPSA/tPSA, maximum flow rate, average flow rate, chest film, abdominal plain film, abdominal b-ultrasound, pelvic MRI, whole-body bone imaging, postoperative recurrence and metastasis, biochemical recurrence, early complications (include postoperative severe hemorrhage, pulmonary infection, heart and lung failure, urinary fistula, intestinal fistula, vesicourethral anastomosis stenosis, urethral stenosis, incontinence, deep vein thrombosis, pulmonary embolism, poor wound healing, lymphocystis, death and so on), pad test results in early postoperative period, treatments, loss to follow-up and death (we indicate the reasons);③datas of three months after operation, include: PSA, fPSA/tPSA, maximum flow rate, average flow rate, chest film, abdominal plain film, abdominal b-ultrasound, pelvic MRI, whole-body bone imaging, postoperative recurrence and metastasis, biochemical recurrence, early complications (include vesicourethral anastomosis stenosis, urethral stenosis, incontinence, erectile dysfunction and so on), pad test results in early postoperative period, treatments, loss to follow-up and death (we indicate the reasons). Therein, erectile function were evaluated just for the patients younger than70years old with satisfactory erectile function preoperative.4Methods of statistical analysis SPSS18.0for windows software package was used for statistical analysis.a=0.05was considered significant. Descriptive statistics data were expressed by frequency or mean+standard deviation. Comparison of rates between two groups were done by chi-squared test or fisher’s exact test, and means were compared by t test. Comparisons of rates among multiple groups were performed using chi-squared test. Spearman rank correlation was used for correlation analysis between ranked data. Kruskal-Wallis H test was used for the difference comparison of some index between unordered data and ranked data, Wilcoxon rank sum test was used for further pairwise comparison (bonferroni was used to adjust α level, a’=0.05/n). Recurrence free survival curves were plotted by kaplan-meier method and compared by the log-rank test. Multivariate survival analysis was performed using cox regression model.Results1Prelimiray clinical effects of technique of DVC ligation free37cases (29.6%) in the group of DVC ligation free while88cases (70.4%) in the group of DVC ligation, the mean operative time was199.5min vs213.6min (t=-1.180, P=0.240), the average bleeding amount was209.5ml vs205.0ml(t=0.111, P=0.912), the average blood transfusion volume was148.7ml vs130.7ml (t=0.408, P=0.685), the transfusion rate was32.4%vs43.2%(χ2=1.254, P=0.263).2The relationship between early continence with different treatments of NVB In the operation, NVB was not preserved in58cases (46.4%), unilateral NVB was preserved in27cases (21.6%) and bilateral NVB were both preserved in40cases (32.0%). The continence rates in three different treatments were respectively70.7%,81.5%,97.5%, not completely consistent (χ2=11.334, P=0.003). The pad test results showed that it is not completely consistent in three different treatments in3months after surgery by means of Kruskal-Wallis H test and Wilcoxon rank sum test (χ2=25.686, P=0.000), while the mean rank order were respectively77.19,61.83,43.21. According to the mean rank order, we inferred that the group of no NVB preserved need most pads in the early postoperative period, the group of unilateral NVB preserved take second place, and then is the group of bilateral NVB preserved. There was no statistical difference between the first two groups (P=0.046>0.025), whlie significant difference was observed between the first and the third group (P=0.000<0.025), and the third group needs less pads. There was also statistical difference between the second and the third group (P=0.006<0.025), and the third group needs less pads. By using the method of spearman rank correlation, it showd that there was a significant negative correlation between the degree of NVB preservation and pads demanding in the early postoperative period (rs=-0.453, P=0.000).3The relationship among preoperative PSA levels, postoperative gleason scores and pathological stages Preoperative PSA:<4.0ng/ml,8cases (6.4%);4.0～10.0ng/ml38cases(30.4%);10.0～20.0ng/ml,34cases(27.2%);>20ng/ml, 45cases (36.0%). Postoperative gleason scores:2-6,67cases (53.6%);7,27cases (21.6%);8,19cases (15.2%);9～10,12cases (9.6%). Postoperative pathological stages:pTl,14cases (11.2%); pT2,75cases (60.0%); pT3,34cases (27.2%); pT4,2cases(1.6%). By using the method of spearman rank correlation, it showd that there is a significant positive relationship between preoperative PSA levels and postoperative gleason scores (rs=0.345, P=0.000), so as preoperative PSA levels and postoperative pathological stages (rs=0.284, P=0.001). Meanwhile, there is a significant positive relationship between postoperative gleason scores and pathological stages (rs=0.642, P=0.000).4Early postoperative complications and long-term outcome Totally57person-time in49patients had10kinds of early complications. Among them: incontinence (at the time of3months after catheter removal),23cases; urinary tract infection,11cases; poor wound healing,7cases; urinary fistula,5cases; urethral stenosis,3cases; vesicourethral anastomosis stenosis,3cases; intestinal fistula,2cases; epididymitis,1case; pulmonary infection,1case; penis and lower extremity lymphoedema,1case. Two and more than two kinds of early complications occurred in7cases:urinary fistula and incontinence,3cases; urinary tract infection and epididymitis,1case; incontinence and poor wound healing,1case; urethral stenosis and vesicourethral anastomosis stenosis,1case; incontinence, urinary tract infection, penis and lower extremity lymphoedema,1case. The continence rates of3months,1year and5years postoperative were respectively81.6%,96.1%,100%. International index of erectile function-5(IIEF-5) were used to evaluate the erectile function for the patients younger than70years old with satisfactory erectile function preoperative,21cases of which were normal and the other42cases were slightly erectile dysfunction. By the end of the follow-up period, recovery of erectile function was found in25cases (39.7%). Among them,2of25cases (8.0%) whose NVB was not preserved,6of12cases (50.0%) whose unilateral NVB were preserved and17of25cases (65.4%) whose bilateral NVB were both preserved had recovered, respectively. Long-term outcome:12cases suffered from bone metastasis,10cases suffered from vesicourethral anastomosis stenosis,5cases suffered from indirect inguinal hernia,5cases suffered from urethral stricture,3cases suffered from vesical calculus,3cases suffered from primary lung cancer,1case suffered from urinary tract infection,1case suffered from calculus of ureter,1case suffered from lung metastasis,1case suffered from bladder cancer,1case suffered from nasopharyngeal cancer and colon-rectal cancer,1case had cerebral thrombosis,1case suffered from acute myocardial infarction and cerebral infarction.6cases died,3of which died of primary lung cancer,2of which died of bone metastasis and1of which died of acute myocardial infarction.5Bio-chemical recurrence free survival analysis Follow-up time ranged from3to126months (mean33months, median24months). Ten patients were lost to follow-up at the time of3rd to105th month postoperation.37cases had bio-chemical recurrence. By single factor analysis, the postoperative bio-chemical recurrence survival time were statistically significant difference among different preoperative PSA, treatments of NVB, lymphatic metastasis, surgical margin, postoperative pathological stages and gleason scores. By multivariate cox regression analysis, surgical margin (HR=3.666,95%CI1.550-8.671), postoperative gleason scores (HR=1.446,95%CI1.140～1.834) and preoperative PSA (HR=1.014,95%CI1.004～1.025) were independent risk factors for the bio-chemical recurrence.ConclusionPreliminary studies showed that the technique of DVC ligation free is an alternative processing method of DVC which is unlikely to increase the risk of bleeding or transfusion compared to DVC ligation, and the former one seems not only much simpler to practise and grasp, but also have a better surgical field and better exposure of the prostate apex because of the help of the tractive force by the pincers. The preservation of bilateral NVB for suitable patients is beneficial for early recovery of urinary continence postoperation. There is a significant positive relationship between preoperative PSA levels and postoperative gleason scores, so as preoperative PSA levels and postoperative pathological stages. The results indicate that preoperative PSA levels is vital to the forecast the postoperative gleason scores and pathological stages. High postoperative gleason score is a independent risk factor of positive surgical margin. Surgical margin, postoperative gleason scores and preoperative PSA were independent risk factors for the bio-chemical recurrence.