Open Anterograde Radical Prostatectomy Compared to Open Retrograde Technique
Condition: Prostatic Cancer; Prostatic Neoplasm
MeSH terms: Prostatic Neoplasms
Study type: Interventional

Summary: 
      Prospective randomized study performing open anterograde anatomical radical retropubic
      prostatectomy (RRP2A) using the same technique of minimally invasive surgery described by the
      Pasadena consensus for the procedure assisted by robot, compared with the anatomical radical
      prostatectomy technique described by Patrick Walsh (RRP). Recent studies have shown benefits
      in the minimally invasive surgical techniques approaches, laparoscopic radical prostatectomy
      (LRP) and, more recently, robot-assisted radical prostatectomy (RARP). These minimally
      invasive techniques were associated with advantages in complications, like intraoperative
      bleeding, transfusion rates and in earlier recovery of important genitourinary functions such
      as urinary continence and penile erection. But still has not been demonstrated conclusively
      advantages as oncological control and it is believed that there are about 200 to 250 cases of
      learning curve so that the rates of complications and positive surgical margins become stable
      and similar to the open radical prostatectomy. These facts associated with the high cost of
      robotic technology still have limited the generalization of this approach in many developing
      countries such as Brazil. While the majority of studies made by comparing the radical
      prostatectomy (RP), robot X laparoscopic X open, show a slight advantage in the first two,
      there is a significant bias in these studies, which is that the surgical technique used in
      each procedure differs significantly from minimally invasive and open surgical techniques.
      The evolution of minimally invasive radical prostatectomy was based on an entirely different
      anatomical benchmark of that described by Patrick Walsh. While robotics and laparoscopic
      techniques dissect the prostate, bladder neck and the neurovascular bundle in an antegrade
      way, from bladder neck to the apex, the Walsh RRP technique is completely different in
      several ways, the dissection is made from prostatic apex to the bladder neck, so the
      retrograde direction, the posterior layer of Denonvilliers' fascia, is always included with
      the specimen, and urethrovesical anastomosis, usually performed with multifilament
      interrupted suture, only for indicating the major differences. The RRP2A will be performed by
      incision (open surgery) and will be compared with the anatomical radical prostatectomy
      technique described by Patrick Walsh RRP, and performed by the same surgeons.
    

Detailed description: 
      Introduction The best way to treat localized prostate cancer is radical prostatectomy (RP).
      This surgery has been performed since 1905, introduced by Young. Initial results were
      disappointing due to high rates of bleeding, incontinence, impotence and other surgical
      complications. It was from the knowledge of the anatomical basis of vascularization and
      innervation of male pelvis by Patrick Walsh that the radical retropubic prostatectomy (RRP)
      had its development and has become the first choice in the treatment of initial stages of
      prostate cancer.

      Large series of literature results show excellent long-term cancer control, with about 80% of
      patients with no evidence of disease (biochemical or clinical) in 10 years.

      Urinary incontinence rates after RRP vary widely, those regarding absence of the urinary
      incontinence after 18 months of surgery are uniform in presenting continence rates above 90%.
      However the continence rates over the short term are much lower.

      The definition of recovery of sexual function after surgery is the ability to keep
      satisfactory sexual intercourse with or without the use of oral drugs. The key factors for
      the recovery of erectile capacity power prior to surgery are the patient's age and the
      surgical technique employed. Academic series of open RRP report recovery rates of about 70%
      with bilateral preservation of nerves, and about 50% with unilateral preservation after 18
      months.

      Recent studies have shown benefits in the minimally invasive approaches, laparoscopic radical
      prostatectomy (LRP) and, more recently, robot-assisted radical prostatectomy (RARP), with
      respect to complications like intraoperative bleeding, but still do not demonstrate
      conclusively advantages as oncological control. However the recovery of erectile function and
      urinary continence seems to recover better and earlier. It is believed that there are about
      200-250 cases of learning curve to reach levels that the rates of complications and positive
      surgical margins become stable and similar to the open radical prostatectomy, and the high
      cost of robotic technology still has limited the generalization of this approach in many
      countries.

      The exponential adoption of minimally invasive robot-assisted radical prostatectomy (RARP)
      has been remarkable and unprecedented. According to unverified estimates from the Da Vinci
      surgical system manufacturer (Intuitive Surgical, Sunnyvale, CA) over 80% of radical
      prostatectomy within the US were performed robotically in 2010. This dramatic shift in
      radical prostatectomy practice patterns occurred despite the lack of evidence of high quality
      of the method, not yet demonstrating its oncology benefits, safety or cost effectiveness
      compared to open surgery.

      While the majority of studies made by comparing the radical prostatectomy: robot X
      laparoscopic X open, show a slight advantage in the first two in regard intraoperative
      complications, especially bleeding, and post operative complications as the speed of recovery
      of continence and sexual potency. There is a significant bias in these studies, which is that
      the surgical technique used in each procedure differs significantly from minimally invasive
      and open surgical techniques. The evolution of minimally invasive prostate surgery was based
      on an entirely different anatomical benchmark of that described by Patrick Walsh for open
      radical prostatectomy.

      While robotics and laparoscopic techniques dissect the prostate, bladder neck and the
      neurovascular bundle, in an antegrade way, from bladder neck to the apex. With careful
      bladder neck dissection and preservation, incremental or not careful nerve-sparing procedures
      with meticulous rectoprostatic dissection of the posterior layer of Denonvilliers' fascia,
      with the aim of maximizing the preservation of the fibers located within the periprostatic
      tissue that covers the lateral and anterior surface of the prostate, and urethrovesical
      anastomosis performed through a monofilament running suture. The Walsh open radical
      retropubic prostatectomy (RRP) technique is completely different in several ways, the
      dissection is made from prostatic apex to the bladder neck, so the retrograde direction, the
      posterior layer of Denonvilliers' fascia is always included with the specimen, and
      urethrovesical anastomosis usually performed with multifilament interrupted suture, only for
      indicating the major differences.

      This trial proposes a prospective randomized study performing radical prostatectomy due to
      open surgery using the same technique of minimally invasive surgery, antegrade, from bladder
      neck to the apex, with careful bladder neck dissection and preservation, incremental or not
      careful nerve-sparing procedures and urethrovesical anastomosis performed by monofilament
      running suture, described by the Pasadena consensus for the procedure assisted by robot.

      A pilot study was performed to test the feasibility of this technique and managed to complete
      ten surgeries in all its stages without conversion to the standard radical prostatectomy
      technique of Patrick Walsh.

      Patients and methods

      This technique will be performed by incision (open surgery) and will be compared with the
      anatomical radical prostatectomy technique described by Patrick Walsh and performed by the
      same surgeons.

      Two hundred and forty patients will be selected with localized prostate cancer with
      indication for radical surgery, confirmed by biopsy and staged as protocol of urology service
      HUPE UERJ of Rio de Janeiro, Brazil.

      Patients will be randomized into two arms, according to the kind of technique, and in three
      sets according to the three different main surgeons. Randomization was performed by software
      on the site "www.randomizer.org/" on November 17, 2015, as follows:

      Arm 1 - open retrograde radical retropubic prostatectomy (RRP).

      Arm 2 - open anterograde anatomical radical retropubic prostatectomy (RRP2A).

      Set 1 - Surgeon A. 1, 1, 2, 2, 1, 2, 2, 2, 1, 1, 1, 2, 1, 1, 1, 2, 2, 1, 1, 1, 1, 2, 2, 1, 2,
      2, 1, 2, 1, 2, 2, 2, 2, 2, 2, 1, 2, 1, 1, 2, 2, 2, 1, 1, 2, 2, 2, 2, 2, 2, 2, 1, 2, 1, 2, 2,
      1, 1, 2, 2, 1, 2, 1, 2, 1, 1, 2, 2, 2, 2, 1, 1, 1, 1, 2, 1, 1, 1, 1, 1

      Set 2 - Surgeon B. 2, 2, 2, 1, 1, 2, 1, 1, 1, 2, 1, 1, 1, 2, 1, 2, 2, 2, 2, 1, 1, 2, 2, 2, 2,
      2, 2, 2, 2, 1, 1, 2, 2, 2, 1, 2, 2, 2, 2, 2, 2, 1, 2, 2, 1, 2, 1, 2, 1, 1, 1, 2, 2, 2, 1, 2,
      2, 2, 2, 1, 2, 2, 2, 2, 1, 1, 2, 2, 2, 2, 2, 1, 1, 2, 2, 2, 1, 2, 2, 1

      Set 3 - Surgeon C. 2, 2, 1, 2, 2, 1, 1, 1, 1, 1, 2, 2, 2, 2, 1, 2, 2, 1, 2, 2, 1, 1, 1, 2, 2,
      1, 2, 1, 2, 2, 2, 2, 2, 1, 1, 1, 2, 2, 2, 1, 2, 1, 1, 2, 1, 2, 1, 1, 1, 2, 1, 2, 1, 1, 1, 2,
      2, 1, 1, 1, 1, 2, 2, 1, 1, 1, 2, 2, 2, 1, 1, 1, 1, 1, 1, 2, 2, 1, 2, 2

      A prostatectomy technique of "open anterograde anatomical radical retropubic prostatectomy
      (RRP2A)" dissects the prostate, bladder neck and the neurovascular bundle, antegrade, from
      bladder neck to the apex, with careful bladder neck dissection and preservation, incremental
      or not careful nerve-sparing procedures with meticulous rectoprostatic dissection of the
      posterior layer of Denonvilliers' fascia, with the aim of maximizing the preservation of the
      fibers located within the periprostatic tissue that covers the lateral and anterior surface
      of the prostate, and urethrovesical anastomosis performed through a monofilament running
      suture, follow the step-by-step described in Pasadena consensus for robot-assisted radical
      prostatectomy and adapted to open surgery.

      Selection of Study Population Patients will be selected with localized prostate cancer
      confirmed by biopsy and staged as protocol of urology service of Pedro Ernesto Hospital of
      State University of Rio de Janeiro, Brazil (HUPE UERJ). All patients with localized prostate
      cancer and indication for open radical retropubic prostatectomy (RRP) will be invited to
      participate in this study.

      The Visits Procedures:

      Day 0. Screening may be performed before or in the same visit of Randomization with the
      patient signed the informed consent before or in the day of surgery.

      Evaluation of inclusion and exclusion criteria. Randomization may also be performed just
      before starting the surgical procedure. Patient identification as age and race, as well data
      as result of the biopsy, prostate specific antigen (PSA) levels and clinical stage are
      transcribed to the protocol. The surgery information is recorded in details at the end of
      surgery. Model protocol annotation form in appendix 1.

      Visit 1 - Day 7 to RRP2A and day 14 for RRP. In this visit the bladder catheter is taken and
      collected information of postoperative complications, time and drainage volume of suction
      drain, wound aspect, length of hospital stay.

      After removal of the bladder catheter will be observed if the patient has a urethral drip or
      if he can retain urine in the bladder.

      PSA dosage will be requested. Visit 2 - Day 30. This visit will be harvested postoperative
      complications information, PSA results and the result of the pathological examination of the
      surgical specimens, prostate, seminal vesicles and pelvic nodes. Evaluation of the surgical
      margins, urethral, bladder and circumferential and pathological staging.

      In this visit will be applied two questionnaires for evaluation of urinary continence and
      sexual function, International Consultation on Incontinence Questionnaire - Short Form
      (ICIQ-SF) and International Index of Erectile Function-5 (IIEF5).

      In this visit the patients will also be asked about their continence, if they are completely
      continent, ie, without the use of any pad, or partial continent, use of only one pad per day
      for protection against accidents. If this one pad is used only to protect any occasional
      urine leakage, but not wets every day, he will be asked how many times a week this pad is
      wet, with the following response options: once, twice, three times or more, almost every day
      or all days of the week. If the patient answers that the pad wets once or twice a week, he
      will be considered partial continent, to answer it wets three or more times, almost every day
      or every day of the week, the patient will be considered incontinent.

      Visit 3 - Day 60. This visit will be harvested postoperative complications information, PSA
      results and the result of the pathological examination of the surgical specimens if these
      results are not ready in the previous visit. Application of the questionnaires ICIQ-SF and
      IIEF5. In this visit will also be asked to the patients about their continence, classified as
      completely continent, partial continent and incontinent. They will be also asked about sexual
      intercourse with penetration and if they are using medication as phosphodiesterase type 5
      (PDE5) inhibitors.

      Visit 4 - Day 90. This visit will be harvested postoperative complications information and
      PSA results.

      Application of the questionnaires ICIQ-SF and IIEF5. In this visit it will also be asked to
      the patients about their continence, classified as completely continent, partial continent
      and incontinent. They will be ask also about sexual intercourse with penetration and if they
      are using medication as PDE5 inhibitors.

      Visit 5 - Day 180. This visit will be assessed the result of PSA. Application of the
      questionnaires ICIQ-SF and IIEF5 and asked to patients about their continence, classified as
      completely continent, partial continent and incontinent. They will also be asked about sexual
      intercourse with penetration and if they are using medication as PDE5 inhibitors.

      Visit 6 - 1 year - End of Study. This visit will be assessed the result of PSA. Application
      of the questionnaires ICIQ-SF and IIEF5 and ask the patients about their continence,
      classified as completely continent, partial continent and incontinent. They will also be
      asked about sexual intercourse with penetration and if they are using medication as PDE5
      inhibitors.
    

Intervention name(s): 1 Retrograde radical prostatectomy RRP; 2 Anterograde radical prostatectomy RRP2A
Intervention type(s): Procedure; Procedure
Intervention description(s): This open surgical technique described by Patrick Walsh involves prostatic dissection made from prostatic apex to the bladder neck, so the retrograde direction, the posterior layer of Denonvilliers' fascia is always included with the specimen, and urethrovesical anastomosis usually performed with multifilament interrupted suture; This open surgical techniques performing radical retropubic prostatectomy using the same technique of minimally invasive surgery, antegrade way, from bladder neck to the apex, with careful bladder neck dissection and preservation, incremental or not careful nervesparing procedures and urethrovesical anastomosis performed by monofilament running suture, described by the Pasadena consensus for the procedure assisted by robot.
Other intervention name(s): Open retrograde radical retropubic prostatectomy (RRP); Open anterograde radical retropubic prostatectomy (RRP2A)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prostatic cancer; Radical prostatectomy; Minimally invasive prostate cancer surgery