Strategies for Improving Erectile Function Recovery After Radical Prostatectomy - DocWire News

Approaches aimed at improving outcomes in the treatment of erectile dysfunction among men undergoing  ) are reviewed in the March 2022 issue of Urologic Oncology: Seminars and Original Investigations.^1-3 In a three-part series, the authors propose a variety of strategies that may be applied in the preoperative,¹ intraoperative,² and postoperative³ settings. They also explore "promising strategies that may inspire future research initiatives in the field."⁴

In an introduction to the series,⁴ senior authors Ashutosh Tewari, MBBS, MCh, FRCS (Hon) and Adriana M Pedraza, MD, from the Department of Urology at Icahn School of Medicine at Mount Sinai, New York, point out that erectile dysfunction associated with radical prostatectomy remains an important issue for men with prostate cancer, despite recent advances in anatomical knowledge.

Although linked to depression and reduced quality of life, erectile dysfunction and its management have received less attention than continence preservation. The authors of the three reviews call for involvement of a multidisciplinary team starting at the time of prostate cancer diagnosis.

Preparing Patients Before Radical Prostatectomy

In the preoperative setting, the strategies proposed are divided into two main categories: comprehensive preoperative planning and prehabilitation programs including metabolic, physical, and social interventions. Magnetic resonance imaging (MRI) is a useful tool in this setting, which, combined with other clinical parameters, permits reliable prediction of non-organ confined disease, the authors state. Multiparametric (mp) MRI gives superior assessment of prostate gland anatomy, although it has low sensitivity for prediction of extracapsular extension (ECE). A new MRI under development, diffusion tensor imaging, may lead to better understanding of periprostatic nerve distribution. A new imaging modality that makes use of a prostate-specific membrane antigen (PSMA) ligand, ⁶⁸Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT), can improve the sensitivity of detecting ECE.

The authors recommend using one of the available nomograms integrating mpMRI with various clinical variables, but they caution that studies are needed to identify the most cost-effective imaging modality in this combination.

Assessment of baseline erectile function may be done using the International Index of Erectile Function Erectile Function (IIEF-EF) questionnaire, but objective parameters to assess baseline erectile function are under investigation, the authors note. They stress the importance of understanding the cultural and psychological background of African American patients who experience disparities in prostate cancer treatment and more often express regret after surgery. Use of the Prostate Cancer Beliefs Questionnaire (PCBQ) can be used to address these issues and reduce racial disparities, the authors suggest.

Prehabilitation involves early identification of and counseling about factors that may inhibit recovery after surgery. These include cardiovascular disease, metabolic syndrome, diabetes, smoking, hyperlipidemia, obesity, and sedentary lifestyle. Pharmacologic treatment may include starting a phosphodiesterase-5 (PDE5) inhibitor such as tadalafil several weeks before surgery.

The authors note the importance of partner sexual function and quality of conjugal relationships for a patient's adherence to a penile rehabilitation program. They stress the value of communication quality, physical health, and mental health of patients and their partners. They rate patient-perceived partner support as an important contributing factor to relationship satisfaction and erectile function suggesting that a complete assessment of the partner's sexual function should be included in current prehabilitation protocols.

Intraoperative Strategies

In the intraoperative scenario, the goal is to achieve negative margins, continence, and return of erectile function. The authors stress that careful surgical technique should be implemented as an intraoperative strategy to optimize functional outcomes. An effort must be made to obtain the best possible nerve-sparing in each patient according to his oncological and baseline functional characteristics, in order to avoid neural-hammock injury, they state.

Precision medicine in the field is leading to intraoperative real-time assessment of surgical margins and prostatic histological architecture to improve the balance between ECE and functional outcomes, the authors note. Technique, tissue handing, avoiding thermal, ischemic, crush or traction injury to the nerves can all play a role in improving erectile function status post prostatectomy. Vascular injuries are likely venogenic due to venous leakage secondary to hypoxia-induced fibrosis.

Robot-assisted radical prostatectomy (RARP) has been associated with mixed results in terms of effects on erectile function compared with open surgery. Several studies have reported faster potency recovery and better erectile function rates and different meta-analyses have suggested superior perioperative and erectile function outcomes in patients undergoing RARP. Various nerve-sparing approaches have been developed based on patient clinical risk stratification or patient anatomy, with no evidence of superiority.

There are several critical steps in the procedure where a traction free and athermal dissection are advised. These include:

• incision of the pelvic fascia (in cases of aggressive disease or a large prostate);
• a non-bladder neck-sparing procedure (to protect the neural hammock)
• vasa deferentia and seminal vesicle dissection
• Denonvilliers fascia incision
• lateral pedicle control
• circumferential apical dissection
• control of the prostatic venous (Santorini) plexus
• urethral anastomosis
• pelvic lymph node dissection (PLND) to avoid injury to the inferior hypogastric plexus

Under review for real-time assessment of positive surgical margins and prostatic histological architecture, intraoperative neurovascular structure-adjacent frozen-section examination (NeuroSAFE) can safely increase nerve preservation while simultaneously improving functional outcomes. Other strategies under investigation include multiphoton microscopy (MPM), confocal laser endomicroscopy (CLE), augmented reality (AR), diffusion tensor imaging (DTI) and spectroscopy. The authors also recommend attempting to preserve the blood supply to the penis, particularly reserving the accessory pudendal artery (APA).

Organ-sparing techniques include removal of the majority of prostatic tissue by robotic surgery, excluding a rim of 5-10 mm of prostate capsule contralateral to the dominant lesion. Preservation of seminal vesicles and ejaculatory ducts are also under investigation. This is based on the assumption that function outcomes will be better if the prostate capsule is preserved. The inflammatory cascade triggered by surgical trauma has been implicated in post-surgical erectile dysfunction and intraoperative hypothermia using an endorectal cooling balloon has been used to counteract this response, with some positive results showing higher erectile function recovery. The viability of the cavemosal nerve stimulation is also being investigated.

Management After Radical Prostatectomy

In the postoperative setting, patients should be managed with early rehabilitation programs, using a multidisciplinary approach to assess the patient's mental, physical, and social well-being, as well as the implementation of pharmacological and mechanical interventions, the authors stress. Pharmacological interventions consist mainly of administration of PDE5 inhibitors. The effectiveness of these drugs after RP is influenced by the grade of nerve-sparing performed. PDE-5 inhibitors have been used in multiple studies in the initial postoperative period, taken either daily or on-demand, with patients on daily doses reporting better international index of erectile function (IIEF) scores.

Intracavernosal injections (ICIs) of the synthetic prostaglandin E1 (PGE1) analog alprostadil, and the medicated urethral system for erection (MUSE) have been shown to be effective in patients with erectile dysfunction. VEDs could assist in preserving penile length and improve sexual function. When used in combination with tadalafil, they have been shown to be associated with significantly higher mean IIEF-5 scores compared with tadalafil alone. Pelvic floor therapy, in addition to its benefit as first-line therapy for on urinary incontinence after RP, has been shown to have a positive effect on erectile function recovery. Another option is implantation of a penile prosthesis, which is associated with a high satisfaction profile.

Since prostate cancer diagnosis and treatment are associated with depression, stress, and anxiety, psychosocial interventions including therapy, partner counseling, and rehabilitation programs, are all important components in the postoperative period. Addressing psychological issues may improve compliance to treatment, the authors note.

Although once believed to be contraindicated, testosterone replacement therapy (TRT) is now considered oncologically safe in patients with prostate cancer after primary treatment for patients appropriate for treatment. Early TRT should be offered to symptomatic hypogonadal men who have no evidence of residual cancer, the authors recommend.

Hyperbaric oxygen therapy (HBOT), low-intensity extracorporeal shockwave therapy (LI-ESWT), and new intracavernosal therapies involving stem cells (Adipose-derived regenerative cells), and nerve-grafting techniques are also under clinical investigation in the postoperative setting.

In summary, patients need to be evaluated in the preoperative, intraoperative, and postoperative settings. Using a multidisciplinary patient-centered approach, including assessment of clinical variables, diagnostic imaging, improvements in surgical technique, and psychosocial and pharmacologic interventions, we can improve patients' sexual function. However, as the authors of these reviews point out, little improvement has been made in sexual function recovery to date and there is still significant research to be done in this area.

David Ambinder, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology. 

References

1. Pedraza AM, Pandav K, Menon M, et al. Current strategies to improve erectile function in patients undergoing radical prostatectomy – preoperative scenario. Urol Oncol. 2022;40(3):72-78. DOIi: 1016/j.urolonc.2021.12.001
2. Pedraza AM, Pandav K, Menon M, et al. Current strategies to improve erectile function in patients undergoing radical prostatectomy – intraoperative scenario. Urol Oncol. 2022;40(3):79-86. DOI: 1016/j.urolonc.2021.12.003
3. Pedraza AM, Pandav K, Menon M, et al. Current strategies to improve erectile function in patients undergoing radical prostatectomy – postoperative scenario. Urol Oncol. 2022;40(3):87-94. DOI: 1016/j.urolonc.2021.12.002
4. Tewari A, Pedraza AM. Introduction to the seminar – Current strategies to improve erectile function in patients undergoing radical prostatectomy (Preoperative, intraoperative and postoperative scenarios). Urol Oncol. 2022;40(3):71. DOI: 1016/j.urolonc.2021.12.020