CLINICAL TRIALS PARTIAL a Randomized Controlled Trial Comparing Pelvic Fascia-sparing and Conventional Radical Prostatectomy
By: Mary Oakley Strasser, MD, MBA, New York-Presbyterian/Weill Cornell Medicine, New York; Andrew Vickers, PhD, Memorial Sloan Kettering Cancer Center, New York, New York; Edward M. Schaefer, MD, PhD, Northwestern University, Chicago, Illinois; Mohamad Allaf, MD, Johns Hopkins University, Baltimore, Maryland; Douglas Scherr, MD, New York-Presbyterian/Weill Cornell Medicine, New York; Keith Kowalczyk, MD, Georgetown University, Washington, DC; Jim C. Hu, MD, MPH, New York-Presbyterian/Weill Cornell Medicine, New York | Posted on: 06 Oct 2023
More than 60,000 men undergo robotic-assisted radical prostatectomy (RP) each year in the United States as treatment for localized prostate cancer.1 The long-term risks of RP include life-long urinary incontinence and erectile dysfunction, as well as penile shortening and deformity (Peyronie’s disease) and inguinal hernias. The pelvic fascia-sparing approach to radical robotic-assisted prostatectomy is a novel surgical technique first described in 2010.2 This posterior approach better preserves native anatomy, including the dorsal vascular complex, nerves, and fascial support structures overlying the anterior prostate, which are severed and removed during conventional RP (Figure 1). Retrospective studies demonstrated lower rates of penile shortening and deformity, attributable, perhaps, to maintaining arterial flow to the penis by preserving the dorsal vascular complex; lower rates of inguinal hernias, attributable to the posterior surgical approach behind the bladder (instead of separating it from the abdominal wall); and more rapid return of urinary continence, attributable to preservation of pelvic fascial support structures.3 An anterior approach to pelvic fascia-sparing has also been described.4 However, preserving the tissue overlying the anterior prostate may risk more positive surgical margins and worse cancer control, especially for men with anterior tumor locations, which is more common in African American patients.5
Currently, evidence quality for pelvic fascia-sparing radical prostatectomy (PFS-RP) is low-grade and largely retrospective. Our published, prospective, parallel comparison of 70 PFS-RPs vs 70 RPs demonstrated that PFS-RP is associated with a lower risk of: urinary incontinence (2% vs 19%); penile shortening (39% vs 67%; P = .02); penile deformity (0% vs 9%; P = .05); and inguinal hernia adverse events requiring surgical repair (0% vs 16%; P < .01). PFS-RPs had similar risk for ED, positive surgical margins, and 12-month prostate-specific antigen recurrence.6 Adequately powered, multisurgeon, multicenter randomized controlled trials (RCT) with longitudinal follow-up are needed to compare the functional and oncologic outcomes of RP and PFS-RP. PFS-RPs currently account for <10% of prostate cancer surgeries, therefore the timing for a multicenter RCT is ideal to evaluate outcomes prior to widespread adoption without sound evidence.7
Historically, standards of surgical care have been accepted without rigorous evidence. While medical and radiation oncologists conduct RCTs comparing various radiotherapy and chemotherapy regimens to iteratively improve outcomes, in surgical oncology, improvements in technique are typically developed by individual surgeons and published as retrospective case series. Unfortunately, randomized comparisons of surgical approaches are challenging to conduct for a variety of reasons. Accrual is often slow and difficult since many patients decline to participate in RCTs, preferring to choose their treatment modalities or finding RCT consents confusing or distressing. Surgeon equipoise may also be difficult to attain, and there may be significant technical variation within a specific technique being compared in contrast to a standard dose of chemotherapy or intensity of radiotherapy. Slow accrual has plagued at least 11 RCTs of novel interventions for prostate cancer that were forced to close prematurely, for example accruing 56 out of a targeted 1,980 patients.8 High trial costs, inadequate research infrastructure for data collection and follow-up, scarcity of funding, and need for large sample sizes are also significant barriers to surgical RCTs.9 In particular, surgical RCTs intended to demonstrate superiority for health-related quality of life (HRQoL) and noninferiority for oncologic outcomes must be powered and large enough to capture small differences in recurrence rates that would offset moderate functional improvements.
Table. Overview of the 24-Month Study Calendar
-365 to 0
|Medical historyb, e||X|
|Physical examc, e||X|
|Assessment of adverse eventsd, e||X||X||X||X||X||X|
|Abbreviations: HRQoL, health-related quality of life; MRI, magnetic resonance imaging; PSA, prostate-specific antigen.
aTo be performed prior to informed consent.
bMedical comorbidities, MRI features (prostate volume and clinical stage), PSA, biopsy characteristics (grade group and tumor volume).
cHeight and weight, evidence of unilateral or bilateral inguinal hernia(s), captured as part of routine medical practice.
dAssessed by operative note and study participant questionnaires. Events are graded using CTCAE v5.0.
eAre not research requirements; are part of standard of care. May vary postoperatively by clinical judgment or by months.
We applied 2 novel approaches to facilitating this large RCT to increase accrual and decrease costs. First, we are using a 2-stage consent process, which aims to reduce information overload and patient decisional burden (Figure 2). This also reduces investigator time burden, as the second consent is only obtained for patients randomized to the intervention arm. Prior studies have demonstrated that this facilitates RCT rapid accrual and maintains patient understanding of trial consent.10 Indeed, a RCT using the 2-stage consent by Vickers et al is ongoing at Memorial Sloan Kettering and New York Presbyterian Weill Cornell on prostate biopsy and radical prostatectomy approaches with >95% enrollment rate and few patients refusing the second consent. Quality of Informed Consent scores have been almost identical to normative data in the literature at 76.0 (95% CI 74.4, 77.5), and consenting professionals report motivation to approach patients for consent has remained high as the process is easier with less anxiety for the patient.
Second, we are incentivizing patient self-reporting through a web portal, Symptom Tracking and Reporting system (STAR), which increases compliance with questionnaire completion and dramatically reduces costs of data collection. This web portal is used by patients as part of routine care and offers individualized clinical and prognostic information based on their responses, for example showing their progress over time and alerting “red flag” symptoms, thereby providing incentive to complete the surveys (Figure 3). By using STAR in routine care, research patients can be confident that their trial participation will not involve additional tests, clinic visits, questionnaires, or appointments. This system is already in use, with over 10,000 RP patients completing outcome questionnaires with a compliance rate at 1-year HRQoL of 75% (without incentives or followup from research staff).
The PARTIAL trial (ClinicalTrials.gov, NCT05155501) is applying these innovative methodical advances in a multi-institutional surgical RCT evaluating the functional and oncologic outcomes of PFS-RP. The target enrollment for the PARTIAL trial is 600 patients over 3 years to achieve 85% power. Men aged 40-85 without a history of previous major pelvic surgery, radiotherapy, or prior focal therapy for prostate cancer are included, and the study duration is 24 months (see Table). The primary outcome is cancer control, and secondary outcomes are HRQoL (sexual and urinary function), decision regret, and adverse events.
Recruitment is ongoing at Northwestern, Johns Hopkins, Georgetown, and Weill Cornell, and we hypothesize that PFS-RP will have similar cancer control and sexual function outcomes with significantly improved urinary function, lower risk of penile shortening/deformity, and lower rates of inguinal hernia compared to conventional RP. In summary, the 2-stage consent and STAR system overcome traditional barriers and expenses to conducting RCTs and have been critical to early enrollment for PARTIAL and other surgical trials.
- Chen J, Oromendia C, Halpern J, Ballman K. National trends in management of localized prostate cancer: a population based analysis 2004-2013. Prostate. 2018;78(7):512-520.
- Lim SK, Kim KH, Shin TY, et al. Retzius-sparing robot-assisted laparoscopic radical prostatectomy: combining the best of retropubic and perineal approaches. BJU Int. 2014;114(2):236-244.
- Huri E. Novel anatomical identification of nerve-sparing radical prostatectomy: fascial-sparing radical prostatectomy. Prostate Int. 2014;2(1):1-7.
- Wagaskar VG, Mittal A, Sobotka S, et al. Hood technique for robotic radical prostatectomy—preserving periurethral anatomical structures in the space of Retzius and sparing the pouch of Douglas, enabling early return of continence without compromising surgical margins. Eur Urol. 2021;80(2):213-221.
- Sundi D, Kryvenko O, Carter H, Ross A, Epstein J Schaeffer E. Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men. J Urol. 2014;191(1):60-67.
- Egan J, Marhamati S, Carvalho FL, et al. Retzius-sparing robot-assisted prostatectomy leads to durable improvement in urinary function and quality of life versus standard robot-assisted radical prostatectomy without compromise on oncologic efficacy: single-surgeon series and step-by-step guide. Eur Urol. 2021;79(6):839-857.
- Kowalczyk KJ. Accessed August 17, 2023. https://twitter.com/KeithKow/status/1237406461686435842?s=20
- Ahmed HU, Berge V, Bottomley D, et al. Can we deliver randomized trials of focal therapy in prostate cancer?. Nat Rev Clin Oncol. 2014;11(8):482-491.
- McCulloch P, Taylor I, Sasako M, Lovett B, Griffin D. Randomised trials in surgery: problems and possible solutions. BMJ. 2002;324(7351):1448-1451.
- Vickers A, Vertosick E, Carlsson S, Ehdaie B, Kim S. Patient accrual and understanding of informed consent in a two-stage consent design. Clin Trials. 2021;18(3):377-382.