More Research Needed to Determine Optimal Management of Complications Due to Salvage Radical Prostatectomy

An estimated 288,000 new cases of prostate cancer will be diagnosed in the United States in 2023.¹ Depending on the risk category of their disease, patients with localized prostate cancer are treated with radiation therapy or prostatectomy, or they undergo active surveillance. After primary localized prostate cancer therapy, an estimated 20% to 40% of patients will experience biochemical recurrence (BCR).² Patients undergoing primary prostatectomy have the option of undergoing salvage radiation therapy; however, the optimal management modality of postprimary radiation therapy prostate cancer recurrence is unclear. One option for management of postradiation recurrence is salvage radical prostatectomy (SRP) in patients with biopsy-proven recurrence after primary radiation.³

Unfortunately, SRP is considered a high-morbidity surgical procedure even in the hands of the most experienced surgeons. Complications include, but are not limited to, rectal injury, urinary incontinence, and fistula formation. Due to the complexity and morbidity of SRP, the literature has been limited to smaller datasets of patients undergoing treatment; however, as the era of robotic surgery has continued to evolve, there has been renewed interest in SRP as a treatment modality. In 2019, Gontero and colleagues provided a contemporary dataset of 395 SRP cases and their postoperative morbidity.⁴ Gontero found that patients undergoing robotic SRP experienced lower blood loss, shorter length of hospital stay, and a lower rate of vesicourethral anastomotic strictures.⁴ Furthermore, the authors reported an overall low rate of rectal injury and fistula formation (<2% for both). Unfortunately, consistent with prior literature, they did find that many patients continued to suffer from severe urinary incontinence, but use of the robotic platform for SRP was found to be an independent predictor of continence preservation.⁴

Recently, Marra and colleagues conducted a systematic review of SRP to further delineate the current status of SRP in the treatment of urologic malignancy.⁵ Unlike single-series data, systematic literature review includes an overall summary of findings from multiple articles and reduces random error and bias by stating explicit criteria for study inclusion.⁵ The authors also indicated they were motivated to conduct this updated review because few of the prior series included a significant number of robotic cases. This point is especially important to consider since the use of the robotic platform has been steadily increasing, with 85% of all robot-assisted laparoscopic radical prostatectomy cases in the primary setting being done robotically in 2013.⁶

The authors conducted a review encompassing articles from over 35 years (1985-2020), garnering data on more than 4000 SRP patients (n=4175). The remarkable component of this analysis was the large number of cases conducted robotically (40%). Furthermore, the authors also included patients who had undergone primary focal therapy as a treatment modality for localized prostate cancer, and those patients comprised 12% of the cohort.

Rectal injury is a dreaded complication of SRP that can lead to infection, abscess formation, or even rectourethral fistula formation, which can be very challenging to manage. Such complications may predispose patients to further pain and discomfort and necessitate the need for further procedures to manage the complications. Although not all articles reported the rate of rectal injury, of the patients who had data present (n=2742), the authors noted a very low rate of rectal injury (0.9%), suggesting that dissection of the prostate off the rectum in the salvage setting can be done safely in the hands of a skilled surgeon. The overall complication rate reported by all studies was 16.1%. The rate of Clavien-Dindo >3 classified complications was even lower (6.6%), although not all studies provided such data.

In terms of functional outcomes—specifically urinary incontinence (UI) and erectile function (ED)—the study provided valuable data on the outcomes of both. UI is thought to occur with more severity during SRP due to a combination of factors, including loss of bladder compliance from radiation therapy, injury to the external urethral sphincter during dissection, and micturition neural injury.³ Although reporting was mixed throughout the studies included, the meta-analysis demonstrated that, consistent with prior reports, less than half of patients at 12 months postsurgery are fully continent (40.4%). The authors noted, however, that patients who had undergone primary focal therapy had a significantly higher rate of urinary control at 12 months (83%), distinct from the remainder of the cohort.

Another point of interest with regards to urinary continence is the utilization of the Retzius-sparing robotic approach, wherein the surgeon approaches the prostate posterior to the bladder near the pouch of Douglas and completes the prostatectomy without entering the space of Retzius. Compared with the traditional approach, the Retzius-sparing technique is thought to facilitate an earlier return of complete continence.⁷ The meta-analysis noted that SRP was conducted using the Retzius-sparing approach in at least 1 study, and the authors of that study noted lower postoperative pad use, suggesting that Retzius-sparing SRP may be a feasible approach, even in the salvage setting, with tangible continence benefits.

Erectile function is another significant outcome of concern for patients. Like primary prostatectomy, SRP runs the risk of injury to the neurovascular bundle during dissection and may further contribute to pre-existing fibrosis and atrophy of the corpora cavernosa. Dissection in a preirradiated field can prove challenging even in the hands of an experienced surgeon. Although not every study provided comprehensive data on the subject, Marra et al noted that at 12 months, the potency rate (spontaneous or via PDE5) was <16%. Two studies reported pre-SRP potency rates of 65% to 67%, which subsequently fell to 11% to 14% at 12 months after SRP.

The postsurgical treatment of functional outcomes such as UI and ED after SRP remains a challenge for all urologists who perform SRP. The data provided by this meta-analysis highlight the importance of discussing the realistic post-SRP outcomes with patients who are interested in pursuing SRP after primary radiation or focal therapy. Further studies are needed to elucidate the optimal management of such complications; however, reassuringly, the data from this analysis demonstrate that the most dreaded complications—rectal injury, for example—remain rare, and the use of the robotic approach may facilitate better perioperative and postoperative outcomes.

Akhil Abraham Saji, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include urology education and machine learning applications in urologic care. He is a founding and current member of the EMPIRE Urology New York AUA section team.

References

1. Cancer Stat Facts: prostate cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Accessed May 14, 2023. https://seer.cancer.gov/statfacts/html/prost.html
2. Simon NI, Parker C, Hope TA, Paller CJ. Best approaches and updates for prostate cancer biochemical recurrence. Am Soc Clin Oncol Educ Book. 2022;42:352-359. doi:10.1200/EDBK_351033
3. May DN, Parker WP. Review of principles of salvage radical prostatectomy. AME Med J. 2021;6:3. doi:10.21037/amj-20-60
4. Gontero P, Marra G, Alessio P, et al. Salvage radical prostatectomy for recurrent prostate cancer: morbidity and functional outcomes from a large multicenter series of open versus robotic approaches. J Urol. 2019;202(4):725-731. doi:10.1097/JU.0000000000000327
5. Marra G, Marquis A, Yanagisawa T, Shariat SF, Touijer K, Gontero P. Salvage radical prostatectomy for recurrent prostate cancer after primary nonsurgical treatment: an updated systematic review. Eur Urol Focus. 2023;9(2):251-257. doi:10.1016/j.euf.2023.01.013
6. Leow JJ, Chang SL, Meyer CP, et al. Robot-assisted versus open radical prostatectomy: a contemporary analysis of an all-payer discharge database. Eur Urol. 2016;70(5):837-845. doi:10.1016/j.eururo.2016.01.044
7. Nyarangi-Dix JN, Görtz M, Gradinarov G, et al. Retzius-sparing robot-assisted laparoscopic radical prostatectomy: functional and early oncologic results in aggressive and locally advanced prostate cancer. BMC Urology. 2019;19(1):113. doi:10.1186/s12894-019-0550-9