Extraperitoneal SINgle-site rObotic-assisted radical prostatectomy (RARP) versus transperitoneal multi-site RARP in the Treatment Of Prostate cancer (SINO-TOP): a multicenter, non-inferiority, randomized controlled trial study design

Extraperitoneal SINgle-site rObotic-assisted radical prostatectomy (RARP) versus transperitoneal multi-site RARP in the Treatment Of Prostate cancer (SINO-TOP): a multicenter, non-inferiority, randomized controlled trial study design | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Extraperitoneal SINgle-site rObotic-assisted radical prostatectomy (RARP) versus transperitoneal multi-site RARP in the Treatment Of Prostate cancer (SINO-TOP): a multicenter, non-inferiority, randomized controlled trial study design Duocai Li, Zhiguo Fan, Yihaoyun Lou, Weidong Xu, Ye Wang, Zhixiang Xin, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7595323/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Radical Prostatectomy is the standard treatment for localized prostate cancer. Compared to open or laparoscopic approaches, multi-site robotic-assisted radical prostatectomy (msRARP) has been proved to improve postoperative functional recovery, tumor control and fewer surgical complications. With advancements in robotic surgical hardware and technology, single-site Vattikuti Institute Prostatectomy (VIP) (ss-RARP) enables the preservation of potency and reduction of surgical trauma through a single small incision and extraperitoneal access, thus achieving more satisfying clinical outcomes. Consequently, ssRARP is currently being widely promoted for application. However, its definitive clinical value requires rigorous validation. Therefore, our study is designed to clarify the non-inferiority of ssRARP over msRARP in terms of functional recovery, key perioperative indicators and tumor control by conducting a large-scale randomized controlled trial (RCT). Methods This study is designed as a multicenter and non-inferiority randomized controlled trial. Centers with an annual caseload of > 100 RARP volume are qualified to include patients after informed consent has been given. Surgeons must have ample experience performing RARP, including an annual caseload of 40 ssRARP procedures. A total of 480 (2 × 240) patients will be enrolled from 5 participating centers, and each center will randomly allocate patients to either the ssRARP group or the msRARP group at a 1:1 ratio. Patients’ baseline, clinical, and surgical data will be closely recorded, and follow-up visits will be scheduled at 1, 3, 6 and 12 months postoperatively. During each follow-up visit, the patients’ clinical outcomes were recorded. The impact on the functional recovery rate and PSA level will be calculated as the average difference between the groups with 95% confidence intervals. Conclusion This study is designed to clarify the clinical value of robotic radical prostatectomy with VIP techniques and to contribute to the development of evidence-based guidelines concerning surgical management for localized prostate cancer. Trial registration: Clinical trial identification number: NCT06238713. Registered on 2 February 2024. Robotic surgery Vattikuti Institute Prostatectomy Complications Potency Figures Figure 1 Background Prostate cancer is the second most lethal malignant tumor in men worldwide[ 1 ] and one of the fastest growing malignant tumours in terms of incidence in China's first-tier cities [ 2 ]. Patients with localized prostate cancer receive radical prostatectomy (RP) as a standard treatment [ 3 ]. In the past decade, robotic radical prostatectomy (RARP) has demonstrated advantages in terms of tumor control, continence recovery and potency recovery over open (ORP) or laparoscopic radical prostatectomy (LRP) [ 4 – 6 ] and has been applied to more than 80% of radical prostatectomy procedures in clinical practice [ 7 ]. Benefiting from the awareness of early diagnosis for prostate cancer, more patients are initially diagnosed at a younger age[ 8 ], whose higher demands are put forward for receiving a more satisfying postoperative quality of life. Therefore, the application of robot-assisted single-site laparoscopic radical prostatectomy has become desirable[ 9 ]. The idea of laparoendoscopic single-site surgery (LESS) was first reported in 2009 by performing RARP through a single but small incision around the umbilicus or lower abdomen, after which all patients had a visual analogue score of 0/10 in one week[ 10 ]. This operation then evolved in the past decade[ 11 , 12 ]. Our team reported the world’s first single-site extraperitoneal robotic-assisted radical prostatectomy with Vattikuti Institute Prostatectomy (VIP) techniques, hereinafter referred to as ssRARP, in which 96.4% and 30.23% of patients had satisfactory continency and potency recovery outcomes, respectively[ 13 ]. However, the ssRARP faces common problems such as limited operating space, instrument collision and crossover, and loss of the operating triangle. To clarify the applicable value and whether ssRARP is inferior to multi-site transperitoneal robotic radical prostatectomy with bilateral intrafascial nerve-sparing techniques (hereafter referred to as msRARP) in terms of patient tumor control, intraoperative margin positivity, postoperative continence recovery, potency recovery, complication rates, etc., rigorous, real-life, large-sample data are needed. Existing knowledge RARP is based on the surgical robotic platform, such as da Vinci Xi or Si system, which comprises a finely rotatable robotic arm and a 3D camera that can be magnified 5–10 times in the narrow pelvic area for dissection and anastomosis and prevent staunch bleeding[ 6 ]. Therefore, RARP has led to a significant reduction in hemorrhage during surgery, a decrease in the positive margin rate postoperatively, improved suture efficiency, shortened the operative time, and minimized the incidence of complications[ 14 ]. Moreover, since multiple port laparoscopic surgeries require several (usually 3–5) operative orifices in the abdominal wall, each additional operative orifice increases the potential risk of bleeding, injury to abdominal organs, incisional hernia, etc., and results in unfavourable aesthetics of the incision[ 15 ]. However, single-site RARP has been reported to have better continence and potency recovery[ 16 – 18 ] because single-site RARP is performed by three inserted articulated endoscopic instruments and an articulated endoscopic camera into the patient’s abdomen via a hidden and single robotic port [ 19 ]. To further promote functional recovery and reduce clinical complications, our team launched the world’s first extraperitoneal ssRARP, in which the retroperitoneal space was established via the use of a sterile surgical glove repurposed as a dilation device. Following systematic expansion, a standardized 10-cm multichannel laparoscopic port was deployed beneath the rectus abdominis sheath through a muscle-splitting technique under direct visualization[ 20 ]. Afterwards, the Vattikuti Institute Prostatectomy (VIP) technique[ 21 ] was implemented to accomplish ssRARP. This operation is believed to be accessible for patients with a history of abdominal surgeries and intraperitoneal adhesions. The use of extraperitoneal access eliminates the need for steep Trendelenburg positioning, which significantly reduces postoperative facial edema and airway swelling, thereby promoting accelerated functional recovery[ 20 , 22 ]. Although ssRARP is expected to further reduce surgical trauma and perioperative complications, there is still a lack of credible evidence to demonstrate the non-inferiority of ssRARP to msRARP. Objective This project aims to clarify the non-inferiority of ssRARP to msRARP, which is based on the existing robotic platform by recruiting the patients from urology centers of 5 well-known tertiary hospitals in China, which have already carried out single-site robotic radical prostatectomy on a routine basis, and to lead a large-sample, multicenter, prospective, randomized, controlled clinical study. In each center, 80 prostate cancer patients were enrolled and randomly assigned at a 1:1 ratio to receive single-site robotic extraperitoneal VIP radical prostatectomy (super-veil nerve sparing) or multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve-sparing). High-level evidence-based medical evidence was subsequently obtained through close recording of perioperative data and postoperative follow-up data and rigorous follow-up on the basis of the PC-Follow national multicenter online specialized disease database to further identify and validate the potential advantages of single-site extraperitoneal VIP robotic radical prostatectomy in terms of short-term urinary continence and potency recovery, as well as the potential advantages in terms of tumor control, overall postoperative continence, potency, margin positivity, and complications incidence, and other dimensions. This technique is expected to further improve the popularity and accessibility of single-site robotic radical prostatectomy. Methods Study design This study is a two-arm randomized controlled clinical trial on whether single-site extraperitoneal VIP RARP is noninferior to multi-site transperitoneal RARP in terms of the functional recovery rate and key clinical metrics. Patient recruitment is currently being conducted at the urology departments of the five top-ranked hospitals in China. Each center performs both the ssRARP and the msRARP, and patients are allocated randomly at a ratio of 1:1. Centers can only perform operations on existing robotic systems. To prevent learning curve bias, only centers and surgeons who performed at least 40 ssRARP procedures were eligible to participate. After meeting the eligibility criteria for clinical trial enrollment, the principal investigator, in compliance with hospital ethics, discusses the benefits and risks of participation with the patient and their family. Upon obtaining written informed consent from the patient and their family, the patient is enrolled in the trial and proceeds to the screening phase. Characteristics of participants Inclusion criteria Patients eligible for the trial must comply with all of the following: Men aged 18 years ≤ age ≤ 75 years; Prostate biopsy within 6 months of diagnosis of organ-confined prostate cancer with preoperative staging of T1c to T2b, N0M0; Gleason score (GS) < 8; PSA ≤ 20 ng/ml; Pathologic diagnosis of prostate adenocarcinoma or prostate ductal adenocarcinoma; The patient is able to have intercourse before surgery and intend for sexual activities after surgery; Physiological conditions acceptable for laparoscopic surgery; Willingness to cooperate and complete the study follow-up and related examinations; The subject or his agent voluntarily participates in this trial and provides written informed consent; The questionnaire can be completed in Chinese; The patient was informed of the trial. Exclusion criteria: When a patient meets one of the following exclusion criteria, they will be excluded from participation: High-risk and non-organ-confined prostate cancer (clinical stage ≥ T2c, GS ≥ 8, PSA > 20 ng/ml); Low or intermediate risk prostate cancer with > 5% risk of lymph node metastasis as assessed by the Briganti scale; Special types of prostate cancer, such as neuroendocrine prostate cancer; History of previous abdominal surgery and radiotherapy, which may affect the abdominal incision and port placement; Recent surgery of the rectum, perianal abscess or around the fistula and perineal area; Patients who have undergone previous transurethral resection/enucleation of the prostate; Nonrecurrent patients with less than 12 months of follow-up; ECOG > 1; Combinations of other systemic tumors; Had received any type of preoperative antitumour therapy; A poor general condition with one of the following conditions: severe mental disorders, cardiovascular disease, active infections, bone marrow transplantation within 3 months, or significant abnormalities in organ function; Participation in other clinical studies or previous treatment with any gene therapy product within the last 3 months; Other conditions that the researchers believe may affect the experimental results or are unethical. Interventions Overall, the surgical techniques for ssRARP or msRARP will follow our standardized operation procedures (SOPs). In ssRARP group, patients will undergo single-site extraperitoneal robotic-assisted radical prostatectomy with Vattikuti Institute Prostatectomy (VIP) techniques (super-veil nerve-sparing). In msRARP group, multi-site transperitoneal robotic radical prostatectomy with bilateral intrafascial nerve-sparing techniques will be performed. Both groups will be operated by da Vinci Si/Xi systems, and no new surgical robots will be purchased. All cases will undergo radical prostatectomy without lymph node dissection after being assessed by the Briganti scale. All procedures were conducted by a group of fixed and experienced console surgeons in each center. A consistent surgical team (bedside assistants and scrub nurses) was maintained throughout the study. The number of ssRARP and msRARP patients enrolled will be 480 in total, with a ratio of 1:1, and the surgeons should be experienced with at least 40 single/multiple-site RARPs. Each center performs surgical and perioperative management according to SOP standards to prevent bias due to different perioperative protocols. Outcomes Primary endpoint Postoperative potency at 3 months was determined as the primary endpoint, defined by the patient's self-evaluation of whether the erection was firm enough for sexual activity or intercourse. Key secondary endpoints Postoperative continence at 3 months was determined as the key secondary endpoint, which was assessed on the basis of the number of pads used per day. Continence after RP should be defined as total control without any pads or leakages[ 23 ]. Secondary endpoints 1. The rate of recovery of urinary continence was assessed at 1, 6, and 12 months postoperatively and was assessed on the basis of the number of pads used per day. 2. The rate of potency recovery was assessed at 6 and 12 months postsurgery by the patient's self-evaluation of whether the erection was firm enough for sexual activity or intercourse, the IIEF-5 score, with or without PDE-5 inhibitor intake. 3. PSA level was assessed postoperatively at a frequency of 1, 3, 6 and 12 months. 4. The Clavien‒Dindo complication score[ 24 ] was measured every day during the period of hospitalization (up to 7 days). 5. The operative time, the time elapsed from the skin incision to the placement of the final skin suture, was measured in minutes and recorded. 6. The volume of estimated blood loss was measured and recorded during the operation. 7. The period of hospitalization was defined as the number of days from the first day of hospitalization to discharge. 8. The period of postsurgery hospitalization was considered the number of days from the time of transfer to the postanaesthesia care unit (PACU) to discharge. Patient-reported outcomes Patients were asked to complete 3 questionnaires at 4 different time points, including the Pain Score Visual Analogue (VAS), the World Health Organization on Quality of Life Brief Scale (WHOQOL-BREF), and the International Index of Erectile Function (IIEF-5) Questionnaire. Each questionnaire took approximately 5 minutes to complete before surgery and 1 month, 3 months, 6 months and 12 months after surgery. Descriptions of whether erections are firm enough for sexual activity or intercourse, IIEF-5 scores, and PDE-5 inhibitor intake will be used to evaluate the postoperative recovery of potency. In addition, patients will be asked to record the number and weight of postoperative urinary pads used. Clinical outcomes Clinical data were recorded by the investigators via an electronic case report form (eCRF). The clinical data included baseline, perioperative, and clinical follow-up data, which were collected at 1, 3, 6, and 12 months after surgery. The data collection timeline is shown in Table 1 . Table 1 Standard Protocol Items Study period Enrolment Allocation Hospitalization Follow-up Close-out Timeline SS/MS RARP Post-surgery hospitalization 1 month 3 months 6 months 12 months Timepoint -t₂ -t₁ t₀ t₁ t₂ t₃ t₄ t₅ Enrolment: Eligibility assessment √ Informed consent √ Randomization √ Intervention: ssRARP or msRARP √ Assessments: Baseline data √ Clinical data √ Pathological data √ √ Surgical data √ Patient reported data √ √ √ √ √ √ Potency Recovery √ √ √ Continence Recovery √ √ √ √ √ PSA status √ √ √ √ √ Imagological examination √ √ a. Baseline: vital signs, history of any previous abdominal surgery, eligibility; b. Allocation; c. Clinical: Grading of postoperative complications (Clavien‒Dindo), postoperative complications, number of days in the hospital, postoperative time to postoperative flatus/g ambulation/drainage removal/urinary catheter removal, pain assessment on the day of discharge (0–10), perioperative use of pain medication, type of pain reliever (nonsteroidal/steroidal/others), cost of hospitalization, cost of surgery, and days to removal of the urinary catheter; d. Pathology: biopsy reposts and preoperative pathologic staging, postoperative specimen pathological results, preoperative pathological staging, and surgical resection status; e. Surgical: Date of surgery, type of access, surgical platform, location of the incision, type of port, diameter of the port, surgical access, operative time/min, up time/min, nerve preservation, unilateral/bilateral nerve preservation method, intraoperative hemorrhage, transfusion, amount of blood transfused/ml, transfer to other surgery, whether additional operative holes were added, other intraoperative complications, and drainage tube application; f. Reported: Health-related quality of life, VAS score, postoperative potency (including description of erections firm enough for sexual activity or intercourse, IIEF-5 score, and PDE-5 inhibitor intake); g. Continence Recovery: pad usage, number and weight (g/pad); h. Imagological examination: ECT/PET-CT, pelvic/prostate enhanced nuclear magnetic resonance. (ENMR). The perioperative clinical data included surgical information, postoperative outcomes and pathological data. The following surgical parameters were prospectively recorded: date of surgery, type of access, surgical platform location of the incision, type of port, diameter of the port, surgical access, operative time/min, up time/min, nerve preservation, unilateral/bilateral/superveil nerve preservation method, intraoperative hemorrhage, transfusion, amount of blood transfused/ml, conversion to other surgery, intraoperative complications, and drainage tube application. The operative time was defined as the skin-to-skin surgical time in minutes, excluding the time for anaesthesia preparation. The total operating room occupancy time was also measured. A conversion was defined as an emergent change in the treatment plan to conventional laparoscopic/robotic surgery (i.e., the use of more than one additional port) or to open surgery. Postoperative outcomes are recorded, including grading of postoperative complications (Clavien‒Dindo classification), occurrence of postoperative complications, number of days in the hospital, time to postoperative flatus/ambulation/drainage removal/urinary catheter removal, pain assessment on the day of discharge (on a scale of 0–10), perioperative use of pain medication, type of pain reliever (nonsteroidal/steroidal/others), cost of hospitalization, cost of surgery, and days to removal of the urinary catheter. Pathological data, such as surgical resection data, as well as the pathologic type and stage of the tumor, were obtained from presurgical biopsy reports and postsurgical pathology reports of radical resection samples. Participant timeline Urologic investigators at participating centers will recruit patients who meet the inclusion and exclusion criteria. Information about the rationale and design of the study will be provided. Potential participants will receive an informational letter and informed consent form. Patients will be given sufficient time to consider whether or not to participate. If they agree to participate, they will be instructed sign the informed consent form. Once the patient has signed the informed consent form, their contact information will be transmitted to the coordinating researcher. Patients will undergo surgery at their center within 4–6 weeks of signing the informed consent form. A process map of the SINO-TOP study is shown in Fig. 1 . Sample size This study has a non-inferiority randomized controlled trial design. The experimental group for patients who received single-site robotic extraperitoneal VIP radical prostatectomy, the control group for patients with multi-site robotic transabdominal radical prostatectomy with bilateral intrafascial dissection of NVBs, the research object of the postoperative 3-month recovery rate of potency and continence recovery rate for the observation of the main evaluation index, according to clinical data, is 52%, the experimental group 3-month recovery rate of potency p1 is 52%, the control group 3-month recovery rate p2 is 42% [ 25 ], the bilateral α = 0.05, i.e., unilateral α = 0.025, the grasp degree, i.e., 1-β, is 0.8, the ratio of sample size between the test group and the control group is 1:1, and the non-inferiority cut-off value is -0.05, referring to Chow et al. mentioned in Sample Size Calculation in Clinical Research. At least 240 patients were included in the experimental group and 240 patients were included in the control group, with a total sample size of 480 patients. Sixty patients who underwent single-site extraperitoneal VIP radical prostatectomy for prostate cancer were enrolled in Changzheng Hospital, whereas 60 patients who underwent multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve sparing) were included. Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Sichuan Provincial People's Hospital, The Second Affiliated Hospital of Nanjing Medical University, The First Affiliated Hospital of Guangzhou Medical University, each enrolled 45 patients who underwent single-site robotic extraperitoneal VIP radical prostatectomy and 45 patients who underwent multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve sparing). Recruitment Urologists from 5 centers are involved in patient recruitment. Screening and recruitment will continue until the target population is reached (n = 480). Randomization Randomization will be performed centrally by an independent trial office, and patients will be randomized at a 1:1 ratio to the ssRARP group or the msRARP group. Random assignment will be performed via a randomized numeric table, and all patients and investigators will be aware of the study group assignment. Data collection methods and data management The questionnaires, medical history and clinical data completed by the patients will be registered, processed and stored electronically. The data will be processed according to the medical ethics committees of the centers, and patient data will be anonymized by means of a unique identification code. Statistical methods The impact of surgical complications, disease-free survival rates, transfusion requirements, and surgery-related organ injury will be calculated via differences in proportions and 95% confidence intervals. The influence of surgery on quality of life, postoperative pain, time to resume full activity, surgical duration, and hospital stay will be calculated via the mean difference and 95% confidence intervals. All analyses will be conducted on an intention-to-treat basis. To account for potential confounding factors, including indicator confounding, we employ multivariate regression models and propensity score methods. Additionally, sensitivity analyses will be performed via exclusion methods to illustrate the degree of association between a single unmeasured binary confounder and the intervention and endpoints, thereby adequately explaining the final significant results. Multiple imputation using 10 imputed datasets will be utilized to handle missing data. Data monitoring Participation in this study does not entail additional risks associated with standard treatment. Therefore, a data monitoring committee (DMC) is not needed. However, a data collection monitoring program was developed to 1. Fully monitored informed consent; 2. Monitor the first three patients at each center. If there were no violations, 10% of the patients were randomized to ensure data quality. 3. Validate source data for 10% of the included patients. Ethics and dissemination Research ethics approval and amendments The study protocol, amendment filing, informed consent and patient information booklet were reviewed and approved by the medical ethics committee of each center. The project was registered on clinical trial.gov (NCT06238713) on 2 February 2024. Urologists will inform potential participants of the benefits and potential risks to patients, and informed consent forms for all participants will be provided in duplicate and will be kept and cosigned by the clinician who provides patient information. The results of the study will be made available to participants, healthcare professionals, and the public through newsletters, articles in peer-reviewed journals, and presentations at academic meetings domestically and abroad. Discussion Radical prostatectomy constitutes the primary therapeutic approach for managing localized prostate cancer. Over the past 20 years, radical prostatectomy has undergone a revolution from open surgery and laparoscopic surgery to robotic-assisted prostatectomy. More precise surgical approaches and insidious incisions are expected to help improve postoperative complications such as urinary incontinence and sexual insufficiency, which pose considerable impact on patients’ quality of life after undergoing radical prostatectomy. In the past decade, a growing preference has been seen in more surgeons and patients for minimizing port deposits in RARP, pursuing improved cosmetic outcomes, decreased pain and complications. Furthermore, the extraperitoneal access of ssRARP inherently prevents bowel manipulation and maintains fascial-peritoneal integrity, which mitigates visceral trauma, herniation, and postoperative ileus [ 31 ]. To better evaluate the outcome of single-site and multi-site RARPs, a number of trials had reported similar continence rates at different follow-up time points[ 16 , 17 , 26 – 29 ]. However, due to limitations in sample size, study design, and inconsistency in surgical approach selection, these studies failed to demonstrate significant results on superiority [ 30 ]. Furthermore, the extraperitoneal access of ssRARP inherently prevents bowel manipulation and maintains fascial-peritoneal integrity, which mitigates visceral trauma, herniation, and postoperative ileus [ 31 ] This project aims to provide high-quality evidence through the conduct of a non-inferiority RCT to assist patients and clinicians in making well-informed clinical decisions. A significant strength of this project is that all participating units are high-volume centers for msRARP and ssRARP surgeries within the country, and this represents the first large-scale RCT in China comparing different surgical approaches for RARP. Surgeons performing these operations are required to have at least 40 cases of experience in ss/msRARP surgeries, thereby minimizing biases arising from surgical complexity, experience, and preferences for a particular surgical method. Through this comparative effectiveness study, we compared the outcomes of standardized surgeries performed by surgical teams across five hospitals. The results of this study effectively evaluate real-world effectiveness in daily clinical practice. In addition, the trial does not impose any requirements for the surgical platform applied in ssRARP, which can facilitate the widespread adoption and promotion of the procedure in the future. This flexibility necessitates stringent selection of participating centres and surgeons based on procedural expertise. Currently, there is no definitive conclusion on the superiority or non-inferiority of msRARP/ssRARP, causing confusion for doctors and patients in the choice of surgical treatment methods. We hope to provide constructive suggestions for prostate cancer treatment guidelines through international papers and conference presentations, improving the incidence of perioperative adverse events and postoperative functional recovery rates in patients with prostate cancer. Declarations Trial status Recruitment began in December 2023 and is ongoing. The enrolment process will be completed by June 2025. One-year follow-up and statistical analysis of the last patient is expected to be completed by the end of 2026. Funding This study is supported by Shanghai Shenkang Hospital Development Center (SHDC12022117, SR), National Natural Science Foundation of China (82203138, YC), the 2022 Youth Start-up Fund for Basic Medical Sciences of Naval Medical University (2021QN29, YC), and the Shanghai "Rising Stars of Medical Talents" Youth Development Program (SHWSRS(2025) 071, YC). Authors' contributions S.R. provided study concept, supervised and design the entire project. S.R., Y.C., and D.L (Dong Liu) provided critical guidance and oversight for important intellectual content. D.L. (Duocai Li), Z.F., Y.L contributed equally in conceiving the study idea, study designs, and drafting the manuscript. W.X., W.Y., and Z.X. contributed in study design and project administration. All authors reviewed, edited, and approved the final manuscript. Competing interests The authors declare that they have no conflict of interest. Ethics approval and consent to participate The study protocol, including all amendments, the informed consent form, and patient information report brochure, was rigorously reviewed and approved. Ethical approval for this research was firstly provided by Shanghai Changzheng Hospital Medical Ethics Committee (2023SL073), with formal approval also obtained from the ethics committees at each participating site. The investigation will be carried out in compliance with local legal and regulatory requirements, upholding the ethical standards of the Declaration of Helsinki and consistent with Good Clinical Practice (GCP) guidelines. Patient and public involvement This research was conducted without involvement from patients or the public in the design, or conduct, or reporting, or dissemination plans of this research. Informed consent Potential participants will be notified by the urologist. 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Bhatt NR, Biers S, Sahai A, Belal M, Kozan A, Kujawa M, et al. British Association of Urological Surgeons (BAUS) consensus document on post-prostatectomy incontinence-stress urinary incontinence. BJU Int. 2025 June;135(6):887–901. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205–13. Shikanov S, Woo J, Al-Ahmadie H, Katz MH, Zagaja GP, Shalhav AL, et al. Extrafascial Versus Interfascial Nerve-sparing Technique for Robotic-assisted Laparoscopic Prostatectomy: Comparison of Functional Outcomes and Positive Surgical Margins Characteristics. Urology. 2009 Sept;74(3):611–6. Noh TI, Kang YJ, Shim JS, Kang SH, Cheon J, Lee JG, et al. Single-Port vs Multiport Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Comparative Study. J Endourol. 2022 May;36(5):661–7. Ju GQ, Wang ZJ, Shi JZ, Zhang ZQ, Wu ZJ, Yin L, et al. A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System. Asian J Androl. 2021;23(6):640–7. Lenfant L, Sawczyn G, Aminsharifi A, Kim S, Wilson CA, Beksac AT, et al. Pure Single-site Robot-assisted Radical Prostatectomy Using Single-port Versus Multiport Robotic Radical Prostatectomy: A Single-institution Comparative Study. European Urology Focus. 2021 Sept 1;7(5):964–72. Saidian A, Fang AM, Hakim O, Magi-Galluzzi C, Nix JW, Rais-Bahrami S. Perioperative Outcomes of Single vs Multi-Port Robotic Assisted Radical Prostatectomy: A Single Institutional Experience. J Urol. 2020 Sept;204(3):490–5. Ficarra V, Rossanese M, Ilaria R, Giannarini G, Mottrie A, Thomas C, et al. Impact of transperitoneal anterior, retzius-sparing, extraperitoneal, transvesical and perineal approaches on urinary continence recovery after robot-assisted radical prostatectomy: a systematic review and meta-analysis of comparative studies. Prostate Cancer Prostatic Dis. 2025 June;28(2):328–41. Akand M, Erdogru T, Avci E, Ates M. Transperitoneal versus extraperitoneal robot-assisted laparoscopic radical prostatectomy: A prospective single surgeon randomized comparative study. Int J Urol. 2015 Oct;22(10):916–21. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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14:22:12","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":119889,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7595323/v1/1f9e9e82411eb22892ff41b3.html"},{"id":93338656,"identity":"35fb41a0-d93e-4694-9ca6-7e6783c8db3c","added_by":"auto","created_at":"2025-10-12 14:22:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3514781,"visible":true,"origin":"","legend":"\u003cp\u003eProcess map of the SINO-TOP study\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7595323/v1/5d1503ddbc74ecb5f7522c91.png"},{"id":103910172,"identity":"33a78c42-7e59-424a-ac68-7e3fe0f7ddab","added_by":"auto","created_at":"2026-03-04 11:56:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2916490,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7595323/v1/f2f21cf7-2e8e-4875-a9fa-6eb70e4e660d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Extraperitoneal SINgle-site rObotic-assisted radical prostatectomy (RARP) versus transperitoneal multi-site RARP in the Treatment Of Prostate cancer (SINO-TOP): a multicenter, non-inferiority, randomized controlled trial study design","fulltext":[{"header":"Background","content":"\u003cp\u003eProstate cancer is the second most lethal malignant tumor in men worldwide[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and one of the fastest growing malignant tumours in terms of incidence in China's first-tier cities [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Patients with localized prostate cancer receive radical prostatectomy (RP) as a standard treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In the past decade, robotic radical prostatectomy (RARP) has demonstrated advantages in terms of tumor control, continence recovery and potency recovery over open (ORP) or laparoscopic radical prostatectomy (LRP) [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and has been applied to more than 80% of radical prostatectomy procedures in clinical practice [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Benefiting from the awareness of early diagnosis for prostate cancer, more patients are initially diagnosed at a younger age[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], whose higher demands are put forward for receiving a more satisfying postoperative quality of life. Therefore, the application of robot-assisted single-site laparoscopic radical prostatectomy has become desirable[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe idea of laparoendoscopic single-site surgery (LESS) was first reported in 2009 by performing RARP through a single but small incision around the umbilicus or lower abdomen, after which all patients had a visual analogue score of 0/10 in one week[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This operation then evolved in the past decade[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our team reported the world\u0026rsquo;s first single-site extraperitoneal robotic-assisted radical prostatectomy with Vattikuti Institute Prostatectomy (VIP) techniques, hereinafter referred to as ssRARP, in which 96.4% and 30.23% of patients had satisfactory continency and potency recovery outcomes, respectively[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, the ssRARP faces common problems such as limited operating space, instrument collision and crossover, and loss of the operating triangle. To clarify the applicable value and whether ssRARP is inferior to multi-site transperitoneal robotic radical prostatectomy with bilateral intrafascial nerve-sparing techniques (hereafter referred to as msRARP) in terms of patient tumor control, intraoperative margin positivity, postoperative continence recovery, potency recovery, complication rates, etc., rigorous, real-life, large-sample data are needed.\u003c/p\u003e"},{"header":"Existing knowledge","content":"\u003cp\u003eRARP is based on the surgical robotic platform, such as da Vinci Xi or Si system, which comprises a finely rotatable robotic arm and a 3D camera that can be magnified 5\u0026ndash;10 times in the narrow pelvic area for dissection and anastomosis and prevent staunch bleeding[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, RARP has led to a significant reduction in hemorrhage during surgery, a decrease in the positive margin rate postoperatively, improved suture efficiency, shortened the operative time, and minimized the incidence of complications[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Moreover, since multiple port laparoscopic surgeries require several (usually 3\u0026ndash;5) operative orifices in the abdominal wall, each additional operative orifice increases the potential risk of bleeding, injury to abdominal organs, incisional hernia, etc., and results in unfavourable aesthetics of the incision[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, single-site RARP has been reported to have better continence and potency recovery[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] because single-site RARP is performed by three inserted articulated endoscopic instruments and an articulated endoscopic camera into the patient\u0026rsquo;s abdomen via a hidden and single robotic port [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. To further promote functional recovery and reduce clinical complications, our team launched the world\u0026rsquo;s first extraperitoneal ssRARP, in which the retroperitoneal space was established via the use of a sterile surgical glove repurposed as a dilation device. Following systematic expansion, a standardized 10-cm multichannel laparoscopic port was deployed beneath the rectus abdominis sheath through a muscle-splitting technique under direct visualization[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Afterwards, the Vattikuti Institute Prostatectomy (VIP) technique[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] was implemented to accomplish ssRARP. This operation is believed to be accessible for patients with a history of abdominal surgeries and intraperitoneal adhesions. The use of extraperitoneal access eliminates the need for steep Trendelenburg positioning, which significantly reduces postoperative facial edema and airway swelling, thereby promoting accelerated functional recovery[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although ssRARP is expected to further reduce surgical trauma and perioperative complications, there is still a lack of credible evidence to demonstrate the non-inferiority of ssRARP to msRARP.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis project aims to clarify the non-inferiority of ssRARP to msRARP, which is based on the existing robotic platform by recruiting the patients from urology centers of 5 well-known tertiary hospitals in China, which have already carried out single-site robotic radical prostatectomy on a routine basis, and to lead a large-sample, multicenter, prospective, randomized, controlled clinical study. In each center, 80 prostate cancer patients were enrolled and randomly assigned at a 1:1 ratio to receive single-site robotic extraperitoneal VIP radical prostatectomy (super-veil nerve sparing) or multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve-sparing). High-level evidence-based medical evidence was subsequently obtained through close recording of perioperative data and postoperative follow-up data and rigorous follow-up on the basis of the PC-Follow national multicenter online specialized disease database to further identify and validate the potential advantages of single-site extraperitoneal VIP robotic radical prostatectomy in terms of short-term urinary continence and potency recovery, as well as the potential advantages in terms of tumor control, overall postoperative continence, potency, margin positivity, and complications incidence, and other dimensions. This technique is expected to further improve the popularity and accessibility of single-site robotic radical prostatectomy.\u003c/p\u003e\u003c/div\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThis study is a two-arm randomized controlled clinical trial on whether single-site extraperitoneal VIP RARP is noninferior to multi-site transperitoneal RARP in terms of the functional recovery rate and key clinical metrics. Patient recruitment is currently being conducted at the urology departments of the five top-ranked hospitals in China. Each center performs both the ssRARP and the msRARP, and patients are allocated randomly at a ratio of 1:1. Centers can only perform operations on existing robotic systems. To prevent learning curve bias, only centers and surgeons who performed at least 40 ssRARP procedures were eligible to participate.\u003c/p\u003e\u003cp\u003eAfter meeting the eligibility criteria for clinical trial enrollment, the principal investigator, in compliance with hospital ethics, discusses the benefits and risks of participation with the patient and their family. Upon obtaining written informed consent from the patient and their family, the patient is enrolled in the trial and proceeds to the screening phase.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCharacteristics of participants\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eInclusion criteria\u003c/h2\u003e\u003cp\u003ePatients eligible for the trial must comply with all of the following:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eMen aged 18 years\u0026thinsp;\u0026le;\u0026thinsp;age\u0026thinsp;\u0026le;\u0026thinsp;75 years;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eProstate biopsy within 6 months of diagnosis of organ-confined prostate cancer with preoperative staging of T1c to T2b, N0M0;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eGleason score (GS)\u0026thinsp;\u0026lt;\u0026thinsp;8;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePSA\u0026thinsp;\u0026le;\u0026thinsp;20 ng/ml;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePathologic diagnosis of prostate adenocarcinoma or prostate ductal adenocarcinoma;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe patient is able to have intercourse before surgery and intend for sexual activities after surgery;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePhysiological conditions acceptable for laparoscopic surgery;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eWillingness to cooperate and complete the study follow-up and related examinations;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e The subject or his agent voluntarily participates in this trial and provides written informed consent;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe questionnaire can be completed in Chinese;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe patient was informed of the trial.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eExclusion criteria:\u003c/h2\u003e\u003cp\u003eWhen a patient meets one of the following exclusion criteria, they will be excluded from participation:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eHigh-risk and non-organ-confined prostate cancer (clinical stage\u0026thinsp;\u0026ge;\u0026thinsp;T2c, GS\u0026thinsp;\u0026ge;\u0026thinsp;8, PSA\u0026thinsp;\u0026gt;\u0026thinsp;20 ng/ml);\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLow or intermediate risk prostate cancer with \u0026gt;\u0026thinsp;5% risk of lymph node metastasis as assessed by the Briganti scale;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSpecial types of prostate cancer, such as neuroendocrine prostate cancer;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHistory of previous abdominal surgery and radiotherapy, which may affect the abdominal incision and port placement;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRecent surgery of the rectum, perianal abscess or around the fistula and perineal area;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients who have undergone previous transurethral resection/enucleation of the prostate;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNonrecurrent patients with less than 12 months of follow-up;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eECOG\u0026thinsp;\u0026gt;\u0026thinsp;1;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCombinations of other systemic tumors;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHad received any type of preoperative antitumour therapy;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eA poor general condition with one of the following conditions: severe mental disorders, cardiovascular disease, active infections, bone marrow transplantation within 3 months, or significant abnormalities in organ function;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eParticipation in other clinical studies or previous treatment with any gene therapy product within the last 3 months;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eOther conditions that the researchers believe may affect the experimental results or are unethical.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInterventions\u003c/h3\u003e\n\u003cp\u003eOverall, the surgical techniques for ssRARP or msRARP will follow our standardized operation procedures (SOPs). In ssRARP group, patients will undergo single-site extraperitoneal robotic-assisted radical prostatectomy with Vattikuti Institute Prostatectomy (VIP) techniques (super-veil nerve-sparing). In msRARP group, multi-site transperitoneal robotic radical prostatectomy with bilateral intrafascial nerve-sparing techniques will be performed. Both groups will be operated by da Vinci Si/Xi systems, and no new surgical robots will be purchased. All cases will undergo radical prostatectomy without lymph node dissection after being assessed by the Briganti scale. All procedures were conducted by a group of fixed and experienced console surgeons in each center. A consistent surgical team (bedside assistants and scrub nurses) was maintained throughout the study.\u003c/p\u003e\u003cp\u003eThe number of ssRARP and msRARP patients enrolled will be 480 in total, with a ratio of 1:1, and the surgeons should be experienced with at least 40 single/multiple-site RARPs. Each center performs surgical and perioperative management according to SOP standards to prevent bias due to different perioperative protocols.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePrimary endpoint\u003c/h2\u003e\u003cp\u003ePostoperative potency at 3 months was determined as the primary endpoint, defined by the patient's self-evaluation of whether the erection was firm enough for sexual activity or intercourse.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eKey secondary endpoints\u003c/h2\u003e\u003cp\u003ePostoperative continence at 3 months was determined as the key secondary endpoint, which was assessed on the basis of the number of pads used per day. Continence after RP should be defined as total control without any pads or leakages[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eSecondary endpoints\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e1. The rate of recovery of urinary continence was assessed at 1, 6, and 12 months postoperatively and was assessed on the basis of the number of pads used per day.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e2. The rate of potency recovery was assessed at 6 and 12 months postsurgery by the patient\u0026apos;s self-evaluation of whether the erection was firm enough for sexual activity or intercourse, the IIEF-5 score, with or without PDE-5 inhibitor intake.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e3. PSA level was assessed postoperatively at a frequency of 1, 3, 6 and 12 months.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e4. The Clavien‒Dindo complication score[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e] was measured every day during the period of hospitalization (up to 7 days).\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e5. The operative time, the time elapsed from the skin incision to the placement of the final skin suture, was measured in minutes and recorded.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e6. The volume of estimated blood loss was measured and recorded during the operation.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e7. The period of hospitalization was defined as the number of days from the first day of hospitalization to discharge.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e8. The period of postsurgery hospitalization was considered the number of days from the time of transfer to the postanaesthesia care unit (PACU) to discharge.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient-reported outcomes\u003c/h2\u003e\n \u003cp\u003ePatients were asked to complete 3 questionnaires at 4 different time points, including the Pain Score Visual Analogue (VAS), the World Health Organization on Quality of Life Brief Scale (WHOQOL-BREF), and the International Index of Erectile Function (IIEF-5) Questionnaire. Each questionnaire took approximately 5 minutes to complete before surgery and 1 month, 3 months, 6 months and 12 months after surgery.\u003c/p\u003e\n \u003cp\u003eDescriptions of whether erections are firm enough for sexual activity or intercourse, IIEF-5 scores, and PDE-5 inhibitor intake will be used to evaluate the postoperative recovery of potency. In addition, patients will be asked to record the number and weight of postoperative urinary pads used.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eClinical outcomes\u003c/h2\u003e\n \u003cp\u003eClinical data were recorded by the investigators via an electronic case report form (eCRF). The clinical data included baseline, perioperative, and clinical follow-up data, which were collected at 1, 3, 6, and 12 months after surgery. The data collection timeline is shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eStandard Protocol Items\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003eStudy period\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEnrolment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eFollow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClose-out\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTimeline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSS/MS RARP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost-surgery hospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTimepoint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-t₂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-t₁\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₁\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₃\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₄\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et₅\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEnrolment:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEligibility assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInformed consent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRandomization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntervention:\u003c/p\u003e\n \u003cp\u003essRARP or msRARP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAssessments:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBaseline data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePathological data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatient reported data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePotency Recovery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eContinence Recovery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSA status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImagological examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ea. Baseline: vital signs, history of any previous abdominal surgery, eligibility;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eb. Allocation;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ec. Clinical: Grading of postoperative complications (Clavien‒Dindo), postoperative complications, number of days in the hospital, postoperative time to postoperative flatus/g ambulation/drainage removal/urinary catheter removal, pain assessment on the day of discharge (0\u0026ndash;10), perioperative use of pain medication, type of pain reliever (nonsteroidal/steroidal/others), cost of hospitalization, cost of surgery, and days to removal of the urinary catheter;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ed. Pathology: biopsy reposts and preoperative pathologic staging, postoperative specimen pathological results, preoperative pathological staging, and surgical resection status;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ee. Surgical: Date of surgery, type of access, surgical platform, location of the incision, type of port, diameter of the port, surgical access, operative time/min, up time/min, nerve preservation, unilateral/bilateral nerve preservation method, intraoperative hemorrhage, transfusion, amount of blood transfused/ml, transfer to other surgery, whether additional operative holes were added, other intraoperative complications, and drainage tube application;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ef. Reported: Health-related quality of life, VAS score, postoperative potency (including description of erections firm enough for sexual activity or intercourse, IIEF-5 score, and PDE-5 inhibitor intake);\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eg. Continence Recovery: pad usage, number and weight (g/pad);\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eh. Imagological examination: ECT/PET-CT, pelvic/prostate enhanced nuclear magnetic resonance. (ENMR).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eThe perioperative clinical data included surgical information, postoperative outcomes and pathological data. The following surgical parameters were prospectively recorded: date of surgery, type of access, surgical platform location of the incision, type of port, diameter of the port, surgical access, operative time/min, up time/min, nerve preservation, unilateral/bilateral/superveil nerve preservation method, intraoperative hemorrhage, transfusion, amount of blood transfused/ml, conversion to other surgery, intraoperative complications, and drainage tube application. The operative time was defined as the skin-to-skin surgical time in minutes, excluding the time for anaesthesia preparation. The total operating room occupancy time was also measured. A conversion was defined as an emergent change in the treatment plan to conventional laparoscopic/robotic surgery (i.e., the use of more than one additional port) or to open surgery.\u003c/p\u003e\n \u003cp\u003ePostoperative outcomes are recorded, including grading of postoperative complications (Clavien‒Dindo classification), occurrence of postoperative complications, number of days in the hospital, time to postoperative flatus/ambulation/drainage removal/urinary catheter removal, pain assessment on the day of discharge (on a scale of 0\u0026ndash;10), perioperative use of pain medication, type of pain reliever (nonsteroidal/steroidal/others), cost of hospitalization, cost of surgery, and days to removal of the urinary catheter.\u003c/p\u003e\n \u003cp\u003ePathological data, such as surgical resection data, as well as the pathologic type and stage of the tumor, were obtained from presurgical biopsy reports and postsurgical pathology reports of radical resection samples.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipant timeline\u003c/h2\u003e\n \u003cp\u003eUrologic investigators at participating centers will recruit patients who meet the inclusion and exclusion criteria. Information about the rationale and design of the study will be provided. Potential participants will receive an informational letter and informed consent form. Patients will be given sufficient time to consider whether or not to participate. If they agree to participate, they will be instructed sign the informed consent form. Once the patient has signed the informed consent form, their contact information will be transmitted to the coordinating researcher. Patients will undergo surgery at their center within 4\u0026ndash;6 weeks of signing the informed consent form. A process map of the SINO-TOP study is shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eSample size\u003c/h2\u003e\n \u003cp\u003eThis study has a non-inferiority randomized controlled trial design. The experimental group for patients who received single-site robotic extraperitoneal VIP radical prostatectomy, the control group for patients with multi-site robotic transabdominal radical prostatectomy with bilateral intrafascial dissection of NVBs, the research object of the postoperative 3-month recovery rate of potency and continence recovery rate for the observation of the main evaluation index, according to clinical data, is 52%, the experimental group 3-month recovery rate of potency p1 is 52%, the control group 3-month recovery rate p2 is 42% [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e], the bilateral \u0026alpha;\u0026thinsp;=\u0026thinsp;0.05, i.e., unilateral \u0026alpha;\u0026thinsp;=\u0026thinsp;0.025, the grasp degree, i.e., 1-\u0026beta;, is 0.8, the ratio of sample size between the test group and the control group is 1:1, and the non-inferiority cut-off value is -0.05, referring to Chow et al. mentioned in Sample Size Calculation in Clinical Research. At least 240 patients were included in the experimental group and 240 patients were included in the control group, with a total sample size of 480 patients. Sixty patients who underwent single-site extraperitoneal VIP radical prostatectomy for prostate cancer were enrolled in Changzheng Hospital, whereas 60 patients who underwent multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve sparing) were included. Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Sichuan Provincial People\u0026apos;s Hospital, The Second Affiliated Hospital of Nanjing Medical University, The First Affiliated Hospital of Guangzhou Medical University, each enrolled 45 patients who underwent single-site robotic extraperitoneal VIP radical prostatectomy and 45 patients who underwent multi-site robotic transperitoneal radical prostatectomy (bilateral intrafascial nerve sparing).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eRecruitment\u003c/h2\u003e\n \u003cp\u003eUrologists from 5 centers are involved in patient recruitment. Screening and recruitment will continue until the target population is reached (n\u0026thinsp;=\u0026thinsp;480).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eRandomization\u003c/h2\u003e\n \u003cp\u003eRandomization will be performed centrally by an independent trial office, and patients will be randomized at a 1:1 ratio to the ssRARP group or the msRARP group. Random assignment will be performed via a randomized numeric table, and all patients and investigators will be aware of the study group assignment.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003eData collection methods and data management\u003c/h2\u003e\n \u003cp\u003eThe questionnaires, medical history and clinical data completed by the patients will be registered, processed and stored electronically. The data will be processed according to the medical ethics committees of the centers, and patient data will be anonymized by means of a unique identification code.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical methods\u003c/h2\u003e\n \u003cp\u003eThe impact of surgical complications, disease-free survival rates, transfusion requirements, and surgery-related organ injury will be calculated via differences in proportions and 95% confidence intervals. The influence of surgery on quality of life, postoperative pain, time to resume full activity, surgical duration, and hospital stay will be calculated via the mean difference and 95% confidence intervals. All analyses will be conducted on an intention-to-treat basis. To account for potential confounding factors, including indicator confounding, we employ multivariate regression models and propensity score methods. Additionally, sensitivity analyses will be performed via exclusion methods to illustrate the degree of association between a single unmeasured binary confounder and the intervention and endpoints, thereby adequately explaining the final significant results. Multiple imputation using 10 imputed datasets will be utilized to handle missing data.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n \u003ch2\u003eData monitoring\u003c/h2\u003e\n \u003cp\u003eParticipation in this study does not entail additional risks associated with standard treatment. Therefore, a data monitoring committee (DMC) is not needed. However, a data collection monitoring program was developed to\u003c/p\u003e\n \u003cp\u003e\u003cspan\u003e1. Fully monitored informed consent;\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e2. Monitor the first three patients at each center. If there were no violations, 10% of the patients were randomized to ensure data quality.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e3. Validate source data for 10% of the included patients.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n \u003ch2\u003eEthics and dissemination\u003c/h2\u003e\n \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\n \u003ch2\u003eResearch ethics approval and amendments\u003c/h2\u003e\n \u003cp\u003eThe study protocol, amendment filing, informed consent and patient information booklet were reviewed and approved by the medical ethics committee of each center. The project was registered on clinical trial.gov (NCT06238713) on 2 February 2024. Urologists will inform potential participants of the benefits and potential risks to patients, and informed consent forms for all participants will be provided in duplicate and will be kept and cosigned by the clinician who provides patient information.\u003c/p\u003e\n \u003cp\u003eThe results of the study will be made available to participants, healthcare professionals, and the public through newsletters, articles in peer-reviewed journals, and presentations at academic meetings domestically and abroad.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e Radical prostatectomy constitutes the primary therapeutic approach for managing localized prostate cancer. Over the past 20 years, radical prostatectomy has undergone a revolution from open surgery and laparoscopic surgery to robotic-assisted prostatectomy. More precise surgical approaches and insidious incisions are expected to help improve postoperative complications such as urinary incontinence and sexual insufficiency, which pose considerable impact on patients\u0026rsquo; quality of life after undergoing radical prostatectomy.\u003c/p\u003e\u003cp\u003eIn the past decade, a growing preference has been seen in more surgeons and patients for minimizing port deposits in RARP, pursuing improved cosmetic outcomes, decreased pain and complications. Furthermore, the extraperitoneal access of ssRARP inherently prevents bowel manipulation and maintains fascial-peritoneal integrity, which mitigates visceral trauma, herniation, and postoperative ileus [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. To better evaluate the outcome of single-site and multi-site RARPs, a number of trials had reported similar continence rates at different follow-up time points[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, due to limitations in sample size, study design, and inconsistency in surgical approach selection, these studies failed to demonstrate significant results on superiority [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, the extraperitoneal access of ssRARP inherently prevents bowel manipulation and maintains fascial-peritoneal integrity, which mitigates visceral trauma, herniation, and postoperative ileus [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThis project aims to provide high-quality evidence through the conduct of a non-inferiority RCT to assist patients and clinicians in making well-informed clinical decisions. A significant strength of this project is that all participating units are high-volume centers for msRARP and ssRARP surgeries within the country, and this represents the first large-scale RCT in China comparing different surgical approaches for RARP. Surgeons performing these operations are required to have at least 40 cases of experience in ss/msRARP surgeries, thereby minimizing biases arising from surgical complexity, experience, and preferences for a particular surgical method. Through this comparative effectiveness study, we compared the outcomes of standardized surgeries performed by surgical teams across five hospitals. The results of this study effectively evaluate real-world effectiveness in daily clinical practice.\u003c/p\u003e\u003cp\u003eIn addition, the trial does not impose any requirements for the surgical platform applied in ssRARP, which can facilitate the widespread adoption and promotion of the procedure in the future. This flexibility necessitates stringent selection of participating centres and surgeons based on procedural expertise.\u003c/p\u003e\u003cp\u003eCurrently, there is no definitive conclusion on the superiority or non-inferiority of msRARP/ssRARP, causing confusion for doctors and patients in the choice of surgical treatment methods. We hope to provide constructive suggestions for prostate cancer treatment guidelines through international papers and conference presentations, improving the incidence of perioperative adverse events and postoperative functional recovery rates in patients with prostate cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecruitment began in December 2023 and is ongoing. The enrolment process will be completed by June 2025. One-year follow-up and statistical analysis of the last patient is expected to be completed by the end of 2026.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is supported by Shanghai Shenkang Hospital Development Center (SHDC12022117, SR), National Natural Science Foundation of China (82203138, YC), the 2022 Youth Start-up Fund for Basic Medical Sciences of Naval Medical University (2021QN29, YC), and the Shanghai \u0026quot;Rising Stars of Medical Talents\u0026quot; Youth Development Program (SHWSRS(2025) 071, YC).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.R. provided study concept, supervised and design the entire project. S.R., Y.C., and D.L (Dong Liu) provided critical guidance and oversight for important intellectual content. D.L. (Duocai Li), Z.F., Y.L contributed equally in conceiving the study idea, study designs, and drafting the manuscript. W.X., W.Y., and Z.X. contributed in study design and project administration. All authors reviewed, edited, and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol, including all amendments, the informed consent form, and patient information report brochure, was rigorously reviewed and approved. Ethical approval for this research was firstly provided by Shanghai Changzheng Hospital Medical Ethics Committee (2023SL073), with formal approval also obtained from the ethics committees at each participating site. The investigation will be carried out in compliance with local legal and regulatory requirements, upholding the ethical standards of the Declaration of Helsinki and consistent with Good Clinical Practice (GCP) guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted without involvement from patients or the public\u0026nbsp;in the design, or conduct, or reporting, or dissemination plans of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePotential participants will be notified by the urologist. Informed consent (Supplementary Material 1) will be obtained from all participants and co-signed by the investigators providing the patient information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209\u0026ndash;49. \u003c/li\u003e\n\u003cli\u003eSchr\u0026ouml;der FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eStolzenburg JU, Holze S, Neuhaus P, Kyriazis I, Do HM, Dietel A, et al. Robotic-assisted Versus Laparoscopic Surgery: Outcomes from the First Multicentre, Randomised, Patient-blinded Controlled Trial in Radical Prostatectomy (LAP-01). Eur Urol. 2021 June;79(6):750\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eJw Y, G C, V P. Level 1 Evidence of Better Early Urinary Continence at 3 Months Following Robot-assisted Laparoscopic Radical Prostatectomy Compared with Laparoscopic Radical Prostatectomy. Results of the LAP-01 Randomised Controlled Trial. European urology [Internet]. 2021 June [cited 2023 Nov 2];79(6). Available from: https://pubmed.ncbi.nlm.nih.gov/33741204/\u003c/li\u003e\n\u003cli\u003eCoughlin GD, Yaxley JW, Chambers SK, Occhipinti S, Samaratunga H, Zajdlewicz L, et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study. Lancet Oncol. 2018 Aug;19(8):1051\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eFahmy O, Fahmy UA, Alhakamy NA, Khairul-Asri MG. Single-Port versus Multiple-Port Robot-Assisted Radical Prostatectomy: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Dec 7;10(24):5723. \u003c/li\u003e\n\u003cli\u003eCornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2024 Aug;86(2):148\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eLee N. Robotic surgery: where are we now? Lancet. 2014 Oct 18;384(9952):1417. \u003c/li\u003e\n\u003cli\u003eKaouk JH, Goel RK, Haber GP, Crouzet S, Stein RJ. Robotic single-port transumbilical surgery in humans: initial report. BJU Int. 2009 Feb;103(3):366\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKaouk J, Garisto J, Bertolo R. Robotic Urologic Surgical Interventions Performed with the Single Port Dedicated Platform: First Clinical Investigation. Eur Urol. 2019 Apr;75(4):684\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eAgarwal DK, Sharma V, Toussi A, Viers BR, Tollefson MK, Gettman MT, et al. Initial Experience with da Vinci Single-port Robot-assisted Radical Prostatectomies. Eur Urol. 2020 Mar;77(3):373\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eChang Y, Xu W, Xiao Y, Wang Y, Yan S, Ren S. Super-veil nerve-sparing extraperitoneal pure single-port robotic-assisted radical prostatectomy on da Vinci Si robotic system. World J Urol. 2022 June;40(6):1413\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eKowalczyk KJ, Huang AC, Hevelone ND, Lipsitz SR, Yu H yin, Ulmer WD, et al. Stepwise approach for nerve sparing without countertraction during robot-assisted radical prostatectomy: technique and outcomes. Eur Urol. 2011 Sept;60(3):536\u0026ndash;47. \u003c/li\u003e\n\u003cli\u003eNovara G, Ficarra V, Rosen RC, Artibani W, Costello A, Eastham JA, et al. Systematic Review and Meta-analysis of Perioperative Outcomes and Complications After Robot-assisted Radical Prostatectomy. European Urology. 2012 Sept;62(3):431\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eMoschovas MC, Bhat S, Sandri M, Rogers T, Onol F, Mazzone E, et al. Comparing the Approach to Radical Prostatectomy Using the Multiport da Vinci Xi and da Vinci SP Robots: A Propensity Score Analysis of Perioperative Outcomes. European Urology. 2021 Mar;79(3):393\u0026ndash;404. \u003c/li\u003e\n\u003cli\u003eVigneswaran HT, Schwarzman LS, Francavilla S, Abern MR, Crivellaro S. A Comparison of Perioperative Outcomes Between Single-port and Multiport Robot-assisted Laparoscopic Prostatectomy. European Urology. 2020 June;77(6):671\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eJu GQ, Wang ZJ, Shi JZ, Zhang ZQ, Wu ZJ, Yin L, et al. A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System. Asian Journal of Andrology. 2021 Dec;23(6):640. \u003c/li\u003e\n\u003cli\u003eKaouk JH, Haber GP, Autorino R, Crouzet S, Ouzzane A, Flamand V, et al. A novel robotic system for single-port urologic surgery: first clinical investigation. Eur Urol. 2014 Dec;66(6):1033\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eChang YF, Gu D, Mei N, Xu WD, Lu XJ, Xiao YT, et al. Initial experience on extraperitoneal single-port robotic-assisted radical prostatectomy. Chin Med J (Engl). 2020 Oct 6;134(2):231\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eGhani KR, Trinh QD, Menon M. Vattikuti Institute Prostatectomy-Technique in 2012. J Endourol. 2012 Dec;26(12):1558\u0026ndash;65. \u003c/li\u003e\n\u003cli\u003eKaouk J, Aminsharifi A, Wilson CA, Sawczyn G, Garisto J, Francavilla S, et al. Extraperitoneal versus Transperitoneal Single Port Robotic Radical Prostatectomy: A Comparative Analysis of Perioperative Outcomes. J Urol. 2020 June;203(6):1135\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eBhatt NR, Biers S, Sahai A, Belal M, Kozan A, Kujawa M, et al. British Association of Urological Surgeons (BAUS) consensus document on post-prostatectomy incontinence-stress urinary incontinence. BJU Int. 2025 June;135(6):887\u0026ndash;901. \u003c/li\u003e\n\u003cli\u003eDindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eShikanov S, Woo J, Al-Ahmadie H, Katz MH, Zagaja GP, Shalhav AL, et al. Extrafascial Versus Interfascial Nerve-sparing Technique for Robotic-assisted Laparoscopic Prostatectomy: Comparison of Functional Outcomes and Positive Surgical Margins Characteristics. Urology. 2009 Sept;74(3):611\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eNoh TI, Kang YJ, Shim JS, Kang SH, Cheon J, Lee JG, et al. Single-Port vs Multiport Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Comparative Study. J Endourol. 2022 May;36(5):661\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eJu GQ, Wang ZJ, Shi JZ, Zhang ZQ, Wu ZJ, Yin L, et al. A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System. Asian J Androl. 2021;23(6):640\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eLenfant L, Sawczyn G, Aminsharifi A, Kim S, Wilson CA, Beksac AT, et al. Pure Single-site Robot-assisted Radical Prostatectomy Using Single-port Versus Multiport Robotic Radical Prostatectomy: A Single-institution Comparative Study. European Urology Focus. 2021 Sept 1;7(5):964\u0026ndash;72. \u003c/li\u003e\n\u003cli\u003eSaidian A, Fang AM, Hakim O, Magi-Galluzzi C, Nix JW, Rais-Bahrami S. Perioperative Outcomes of Single vs Multi-Port Robotic Assisted Radical Prostatectomy: A Single Institutional Experience. J Urol. 2020 Sept;204(3):490\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eFicarra V, Rossanese M, Ilaria R, Giannarini G, Mottrie A, Thomas C, et al. Impact of transperitoneal anterior, retzius-sparing, extraperitoneal, transvesical and perineal approaches on urinary continence recovery after robot-assisted radical prostatectomy: a systematic review and meta-analysis of comparative studies. Prostate Cancer Prostatic Dis. 2025 June;28(2):328\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eAkand M, Erdogru T, Avci E, Ates M. Transperitoneal versus extraperitoneal robot-assisted laparoscopic radical prostatectomy: A prospective single surgeon randomized comparative study. Int J Urol. 2015 Oct;22(10):916\u0026ndash;21. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Robotic surgery, Vattikuti Institute Prostatectomy, Complications, Potency","lastPublishedDoi":"10.21203/rs.3.rs-7595323/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7595323/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eRadical Prostatectomy is the standard treatment for localized prostate cancer. Compared to open or laparoscopic approaches, multi-site robotic-assisted radical prostatectomy (msRARP) has been proved to improve postoperative functional recovery, tumor control and fewer surgical complications. With advancements in robotic surgical hardware and technology, single-site Vattikuti Institute Prostatectomy (VIP) (ss-RARP) enables the preservation of potency and reduction of surgical trauma through a single small incision and extraperitoneal access, thus achieving more satisfying clinical outcomes. Consequently, ssRARP is currently being widely promoted for application. However, its definitive clinical value requires rigorous validation. Therefore, our study is designed to clarify the non-inferiority of ssRARP over msRARP in terms of functional recovery, key perioperative indicators and tumor control by conducting a large-scale randomized controlled trial (RCT).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study is designed as a multicenter and non-inferiority randomized controlled trial. Centers with an annual caseload of \u0026gt;\u0026thinsp;100 RARP volume are qualified to include patients after informed consent has been given. Surgeons must have ample experience performing RARP, including an annual caseload of 40 ssRARP procedures. A total of 480 (2 \u0026times; 240) patients will be enrolled from 5 participating centers, and each center will randomly allocate patients to either the ssRARP group or the msRARP group at a 1:1 ratio. Patients\u0026rsquo; baseline, clinical, and surgical data will be closely recorded, and follow-up visits will be scheduled at 1, 3, 6 and 12 months postoperatively. During each follow-up visit, the patients\u0026rsquo; clinical outcomes were recorded. The impact on the functional recovery rate and PSA level will be calculated as the average difference between the groups with 95% confidence intervals.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003e This study is designed to clarify the clinical value of robotic radical prostatectomy with VIP techniques and to contribute to the development of evidence-based guidelines concerning surgical management for localized prostate cancer.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eClinical trial identification number: NCT06238713. Registered on 2 February 2024.\u003c/p\u003e","manuscriptTitle":"Extraperitoneal SINgle-site rObotic-assisted radical prostatectomy (RARP) versus transperitoneal multi-site RARP in the Treatment Of Prostate cancer (SINO-TOP): a multicenter, non-inferiority, randomized controlled trial study design","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-12 14:22:07","doi":"10.21203/rs.3.rs-7595323/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1f0c3497-4ca2-4b15-a701-20ba15211977","owner":[],"postedDate":"October 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-04T11:54:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-12 14:22:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7595323","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7595323","identity":"rs-7595323","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}