Long-term comparative outcome analysis of a robot-assisted laparoscopic prostatectomy with retropubic radical prostatectomy by a single surgeon

We aimed to report a comprehensive outcome analysis of robot-assisted laparoscopic prostatectomies (RALP) performed by a single surgeon and compared it to retropubic radical prostatectomies (RRP) done by the same surgeon in a high-volume center. Preoperative, perioperative, and postoperative data were collected prospectively and compared with retrospective retropubic radical prostatectomy data. Perioperative, oncological data, and functional results in the first year were compared between the two groups. There were 547 RARPs between 4th August 2011 and 31st December 2018, and 428 RRPs between 1st January 1996 and 31st December 2009 which were included in this review. While the operation time was in favour of the open group (196 vs 160 min, p < 0.01), the estimated blood loss (188 vs 316 ml, p < 0.01), blood transfusion rate (3% vs 7%, p = 0.021), hospital stay (4 days vs 7 days), and mean catheter duration (12 vs 15 days) were in favour of the robotic group. Majority of the complications belonged to Clavien–Dindo group II in both groups and the rates were not significantly different (p = 0.33). The 12-month continence rate was in favour of the RALP group (98.3% vs 99.2%, p < 0.01). Overall survival of the RALP cohort at 24 months was 99.8%, 60 months 96.1%, 84 months 87.3%, 96 months 81.3%), and 108 months was 79.5%. Overall survival at 24 months was 99.8%, 60 months 96.1%, 84 months 87.3%, 96 months 81.3%, and 108 months 79.5%. RALP is a safe, minimally invasive, technically feasible procedure with comparable functional and oncological outcomes. Our study showed superior perioperative and continence outcomes in RALP. However, despite its growing popularity, RRP still remains the gold standard in India due to its affordability and accessibility.


Introduction
The incidence of prostate cancer is rising in India. Overall, it is the third most common cancer in Indian males (1 in 125) and is still a significant cause of cancer-associated death [1]. Increased life expectancy combined with easily available PSA and decreased threshold for biopsy has increased its diagnosis [2]. Radical prostatectomy is the established treatment for localised prostate cancer. The first retropubic radical prostatectomy (RRP) was described by Millin in 1945 [3]. In 1985, Walsh demonstrated the first nerve-sparing retropubic radical prostatectomy [4]. Later in 1997, Schlusser et al. reported a new technique of laparoscopic radical prostatectomy (LRP) [5]. Though the outcomes matched that of RRPs with the added benefit of shorter hospital stay and reduced blood loss, LRP had a long learning curve, which became a limiting factor. In 2000, the first robot-assisted laparoscopic radical prostatectomy (RALP) was performed with greater ease than the LRP, giving a strong impetus to this procedure [6]. Further, high-resolution three-dimensional vision and seven degrees of freedom for manipulation allowed a short learning curve. Although the first RALP in India was performed in the All India Institute of Medical Sciences in 2005 [7], robotic surgery was available at many centres after 2010. The SWOT analysis of robot-assisted surgery in India concluded that judicious use and standardised reporting of outcomes were key to the growth of this technology [8].
We report in this study a comprehensive analysis of the 547 RALPs and compare the outcomes to our previous series of 428 open prostatectomies [9]. Our primary aim was to compare the pre-, peri-and postoperative results and functional outcome of the two techniques done by a single surgeon with a follow-up of up to 117 months. Our secondary aim was to analyse the overall and recurrence-free survival of the current series of RALP patients.

Materials and methods
Robotic prostatectomy was done by a single surgeon (JNK) from 4th August 2011 to 31st December 2018. Patients were followed up till 31st October 2021. We compared these cases with our series of 428 open prostatectomy patients from 1st January 1996 to 31st December 2009 by the same surgeon and published earlier [9]. Institutional ethics committee approval was obtained. Data acquisition was from case forms, which were filled at regular intervals at admission and during subsequent follow-ups. The case report forms catalogued the demographic parameters such as age, comorbidities, clinical variables, including prostate-specific antigen studies, biopsy Gleason score, clinical stage, pathological Gleason score and pathological staging, as well as the total operative time, perioperative complications, hospital stay, blood loss, the requirement for blood transfusion, and duration of the catheter. Complications were tabulated and classified based on Clavien-Dindo classification [10]. Details of histopathologic assessment included final Gleason score, margin positivity, and seminal vesicle and lymph node involvement.
Gleason grade grouping was done according to grade group I (3 + 3), grade group II (3 + 4), grade group III (4 + 3), grade group IV (8), and grade group V (9-10). Patients were followed up at 4 weeks first, then 3 monthly for 2 years, and 6-monthly till 5 years and annually after that. We obtained clinical history, imaging, PSA level, and information on potency and continence at each visit. We defined continence as wearing 0 pads or a one-liner throughout the day. A PSA above 0.2 ng/ml was defined as biochemical recurrence. Adjuvant hormone therapy was given to patients with lymph node involvement and patients who developed metastasis.

Methods
Da Vinci ® Si ™ system (Intuitive Surgical, Sunnyvale, CA) was used from 2011 to 2015 and Da Vinci ® SHD from June 2015 to December 2019. The conventional transperitoneal six-port approach was performed in all cases described by Vatikutti Institute [11] in the first 100 cases. In the subsequent 447 cases, the surgeon used Montsouri's laparoscopic technique with robotic modification [12]. Neurovascular bundle preservation was assessed according to the D'Amico risk classification and MRI. Urethrovesical anastomosis was modified using Van Velthoven's technique [13]. Modified posterior reconstruction of the rhabdosphincter was done in all cases. A 22 F Foleys catheter was kept, and normal saline of 200 ml was instilled for the anastomosis challenge. The postoperative pathway included early ambulation without assistance, early resumption of oral diet, and reasonable pain control. The urethral catheter was removed within 21 postoperative days.

Data analysis
R Core Team (2021) software was used for data analysis. Continuous variables were presented as mean and standard deviation, and categorical variables as a percentage. Numerical parameters between the two groups were compared with Student's t test or the Mann-Whitney U test. A p value < 0.01 was accepted for statistical significance. Survival analysis in the RALP cohort was done using Kaplan-Meier curves. Multivariate analysis was done using log-rank test. Overall survival was meant as survival from death due to any cause. Recurrence-free survival was defined as patients alive without clinical, pathological, or radiological evidence of disease after radical prostatectomy. Increasing PSA levels, radiological evidence of progressive disease, or death due to any cause was taken as an event. OS and RFS was calculated over 60, 84, and 108 months.

Clinical characteristics
There was no significant difference between the two groups regarding age, BMI, and comorbidities. The preoperative characteristics of the patient population were also similar ( Table 1).

Perioperative characteristics
The intraoperative parameters in terms of mean blood loss, mean operative time, and the total number of patients requiring blood transfusion differed significantly in the two groups. The mean hospital stay and mean catheter duration were also significantly different ( Table 2).

Complications
Complications were classified according to the Clavien-Dindo classification system [10]. The most common   Table 3). The lost needle was retrieved in the same surgery in three cases. However, it prolonged intraoperative time. Four cases were converted to open because of equipment failure in two cases, haemorrhage in one case, and a lost needle in the fourth.
Urine leak was treated by prolonged catheterisation. Lymphocoeles which did not resolve on expectant management were drained using pigtail. Haemostatic clips were detected in three patients, 2-3 months after surgery, and were retrieved cystoscopically. It formed a nidus for vesical calculus in one patient, which was treated with cystolithotripsy 6 months after surgery. Bladder neck contracture was treated cystoscopically with a cold knife.
There was no significant difference in complications between RALP and RRP patients (Table 4).

Pathological results
Standard reporting of radical prostatectomy specimens was followed (according to ADASP guidelines). Histopathology result comparison showed significant difference in lymph node metastasis in the two groups (Table 5).

Continence
There was a significant difference between the 12-month continence rates of the two groups ( Table 6). The time taken by RALP patients to achieve continence is shown in Fig. 1.  (Fig. 3).
In the RRP study, the 7-year overall survival, prostate cancer-specific survival, and event-free survival rate were 83.2%, 82.8%, and 69.9%, respectively. EFS was defined as patients alive without events. Increasing PSA levels or radiological evidence of progressive disease or death due to any cause was taken as an event. Prostate CSS was defined as survival from death attributed to complications of prostate cancer.

Discussion
Since its initial report on a series of 190 patients by Kumar et al. [7], the adoption of RALP in India has been on the rise. With its small incision, RRP remains the procedure of choice for most centres in India due to its cost-effectiveness. We got access to the robotic surgery in the second half of 2011, and from then on the majority of RPs are done robotically; however, open RRPs are still performed by the author (JNK). In the last 25 years (1996-2021), we performed RRPs till 2011 and RALPs after that. Further, we used two types of robots  (SI and SHD). Therefore, we had the chance to compare two large cohorts and report our observations. We also believe our series has the most extensive comparison of RALP with RRP by a single surgeon in India. Demographic and preoperative parameters (Table 1) did not show significant variation in the two patient cohorts despite the patient populations being diagnosed in different periods, except that the number of operations increased over time. Surgical technique-wise (Table 2) RALP clearly showed a significant reduction in blood loss and transfusion rates. Reasons postulated are enhanced visualisation of prostatic apex, exact visualisation of the dorsal venous complex for passage of ligature, and the effect of pneumoperiperitoneum. Reported blood loss in studies ranges from 50 to 2500 ml [14,15]. Our study concurs with literature that RALP is advantageous in blood loss and transfusion rates. Mean surgical duration for RALP reported previously ranges from 105 to 540 min [16,17]. However, in our series, operative time was significantly longer in RALP than RRP, which could be accounted for the time required for docking and getting acquainted with the robotic platform, the learning curve, and initial experience by the surgical team.
Early recovery, minimal ileus, and improved pain control contributed to the statistically significant impact on mean hospital stay between the two groups, which is in keeping with the previous studies [14,18]. This is due to rapid recuperation offered by improved pain control. However, our mean length of stay is longer (4 days) than most series due to patient preference. Ward expenses in Indian patients undergoing RALP are covered by private health insurance in major cities, which partly contributes to a longer stay. Moreover, some patients prefer going home catheter free. In the study by Strother et al. [19], 90% of the cases studied were discharged home within days 0-2. Nelson et al. reported no significant difference between LOS of RRP and RALP patients (1.09 vs 1.03 days) [20].
The catheter duration between the RALP and RRP patients in our study was statistically significant, in favour of RALP patients. Rocco et al. reported that the clinical importance of the difference in catheter duration between robotic and open prostatectomy was limited [15].  We used Clavien-Dindo classification (Tables 3 and 4) as a standardised tool to compare our complications. The difference in the complications between the two groups in our study was not statistically significant. In a prospective trial by Di Pierro et al. [21], significant complication rates for RRP and RALP were 28% and 7%, respectively; minor complication rates were 24% and 35%, respectively [21]. Ryu et al. reported fewer Clavien III complications in RALP than RRP [22]. The difference in the urine leak in the two cohorts was not significant in our study. However, we stopped doing a routine cystogram prior to catheter removal after 100 cases in RALP patients.
Pathological findings of the specimens (Table 5) showed a difference in the positive surgical margin rates between  the groups (17% in RALP vs 23% in RRP). This can be attributed to the superior visualisation of the robotic system, resulting in minor trauma to the prostatic capsule. Di Pierro et al. [21] described PSM rates of 16% in the RALP group, and 32% in the RRP group, Tewari et al. [23] reported 9% in RALP vs 23% in RRP, and Parsons et al. [14] reported no significant difference in the PSM rates between the two groups.
There was a significant difference in the 12-month continence rates favouring the RALP group. This is consistent with the findings of numerous studies in the literature [24,25]. We performed reconstruction of the posterior part of the  Log-rank analysis of variables (clinical T stage, biopsy Gleason grade group, PSA groups, and pathology specimen Gleason grade groups) which had an impact on recurrence-free survival 1 3 rhabdosphincter, as described by Rocco et al. [26], preservation of maximal urethral length by careful apical dissection [27], and watertight urethrovesical anastomosis [15].
Our study is similar to that published by Şimşir et al. who compared 204 RARPs and 755 RRPs from 2007 and 2019 [28]. In their study, the operation time was shorter in the open group (117 vs 188 min), and estimated blood loss (328 vs 150 ml), blood transfusion rate (12 vs 2), and reoperation rate (6 vs 0) were in favour of the robotic group. Mean length of hospital stay, urine leak rate, complication rate, and the 12th-month continence rate were better in the robotic group.
Chen et al. reported 500 RALP cases by one surgeon and analyzed the factors affecting the functional and oncological outcomes. They reported BCR PSA, postoperative Gleason score, and pathological T staging as independent risk factors for BCR [29]. In another study by Asimakopoulos et al. [30], 1627 patients underwent RALP from 2005 to 2010. RFS at 12, 24, 48, and 60 months after RALP were 94.6%, 91.2%, 79.3%, and 73.1%, respectively. PSA, pathologic Gleason score, pathological T staging, and PSM were significant independent predictors of RFS. This is in concordance with our study.
Although the survival curves of the two cohorts in our study were not comparable, the OS at 84 months was similar in both groups (87.3% in RALP vs 83.2% in RRP). This reflects on little or no change in the overall survival of patients undergoing radical prostatectomy, despite difference in the time periods and type of surgery.

Limitations
The study's primary limitation is that it is a prospective case comparison with retrospective cohorts. The cohort was from a different decade where the investigative modalities were not comparable. Although the surgeon is the same, the surgeon's abilities in robotic and open surgeries may be different. Lastly, we could not assess the erectile function of the RALP patients consistently, which could not be incorporated in our study.

Conclusion
In conclusion, our findings demonstrate that RALP is a safe, minimally invasive, technically feasible procedure with comparable functional and oncological outcomes. Our study showed superior perioperative and continence outcomes in RALP. However, despite its growing popularity, RRP remains the gold standard in India due to its affordability and accessibility. Oncological outcomes in both groups remain dependent on clinical and pathological parameters. We believe that case selection and optimisation of costeffective treatment is the necessity of the hour.
Author contributions Both authors contributed to the study's conception and design. Material preparation, data collection and analysis were performed by Jagdeesh Kulkarni. The first draft of the manuscript was written by Neeraja Tillu and both authors commented on previous versions of the manuscript. Both authors read and approved the final manuscript.
Funding This study received no external sources of funding.