Historically, most men who experienced radio-recurrent PCa were subjected to androgen deprivation therapy (ADT) rather than receiving a curative approach. However, recent studies suggest that approximately half of these cases involve localized disease, potentially curable through more aggressive local salvage interventions. Prostate-specific membrane antigen (PSMA)-based imaging has proven useful in identifying these localized recurrences, providing a clearer picture of which patients may benefit from curative treatment rather than palliation.
Salvage Treatments for Radio-Recurrent PCa
Over the past two decades, multiple local salvage strategies have been developed for patients with radio-recurrent PCa. The current systematic review analyzed 28 studies, both prospective and retrospective, involving a total of 1,544 patients. The primary local salvage treatments assessed included brachytherapy (BT), external-beam radiation therapy (EBRT), cryotherapy, high-intensity focused ultrasound (HIFU), and salvage radical prostatectomy (sRP).
Recurrence-Free Survival (RFS)
The review found varying rates of two-year RFS depending on the type of salvage treatment used:
- BT: RFS of 84.0% (95% CI: 67.0%-93.0%)
- EBRT: RFS of 69.0% (95% CI: 42.0%-87.0%)
- Cryotherapy: RFS of 58.0% (95% CI: 43.0%-71.0%)
- HIFU: RFS of 45.0% (95% CI: 38.0%-52.0%)
- sRP: RFS ranged from 75% to 78.5%, with a median follow-up period of 18 to 35 months.
These findings underscore the efficacy of brachytherapy and salvage prostatectomy in achieving favorable oncologic outcomes. However, HIFU and cryotherapy appear less effective based on the RFS data, indicating that these techniques may be better suited for specific patient populations or used in combination with other treatments.
Gastrointestinal Toxicity
The rates of severe gastrointestinal toxicity following each local salvage procedure were also assessed:
- Cryotherapy: 2%
- BT: 3%
- HIFU: 3%
- EBRT: 4%
- sRP: 11%
Challenges in Radio-Recurrent PCa Management
One of the most significant challenges in managing radio-recurrent PCa is the historical tendency to treat these patients with palliative ADT rather than offering them the chance of a curative approach. Studies have shown that many men treated with ADT eventually develop castration-resistant prostate cancer, leading to a poor prognosis. Recent findings from the EMBARK study, which demonstrated improved survival when combining ADT with enzalutamide, have shifted the treatment paradigm somewhat. However, the exclusion of many patients from potentially curative treatment remains a concern.
This reluctance to pursue more aggressive local salvage interventions is rooted in the poor outcomes historically associated with treatments like sRP. Early studies reported high rates of significant complications, including urinary incontinence, rectal injuries, and prolonged healing times. As a result, many urologists have been hesitant to recommend sRP to their patients.
Advances in Salvage Techniques
Despite these challenges, recent advancements in surgical technology and techniques have revitalized interest in salvage radical prostatectomy. The introduction of robotic-assisted platforms has allowed surgeons to perform more precise and less invasive procedures, resulting in improved functional and oncologic outcomes. Several contemporary studies have reported significant reductions in post-operative complications, particularly regarding urinary incontinence and gastrointestinal issues, when compared to earlier sRP series.
Additionally, other local salvage strategies, such as brachytherapy and re-irradiation, have gained traction in the field due to their favorable balance between efficacy and safety. These treatments provide viable alternatives for patients who may not be ideal candidates for salvage radical prostatectomy due to age, comorbidities, or other factors. Focal gland ablation has also emerged as a promising option, although more data are needed to validate its long-term outcomes.
Conclusions and Future Directions
In conclusion, the current systematic review found that prostate salvage re-irradiation via brachytherapy or EBRT offers the best balance of efficacy and safety for patients with radio-recurrent PCa. However, it is important to recognize that the current level of evidence remains low, and there is insufficient data to make strong recommendations regarding any specific local salvage strategy. Consequently, treatment decisions should be made on a case-by-case basis, taking into account the patient's individual disease characteristics, overall health, and treatment preferences.
Moving forward, more high-quality prospective studies are needed to further refine the management of radio-recurrent prostate cancer and provide clearer guidelines for clinical practice. With ongoing advancements in imaging, surgical techniques, and radiation therapy, there is hope that the outcomes for men with recurrent disease will continue to improve in the coming years.
Written by: Massimiliano Creta,1 Shahrokh F Shariat,2 Giancarlo Marra,3 Paolo Gontero,4 Marta Rossanese,5 Simone Morra,1 Jeremy Teoh,6 Amar U Kishan,7 R Jeffrey Karnes,8 Nicola Longo1
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Italy.
- Department of Urology, Medical University of Vienna, Vienna, Austria
- Department of Urology, San Giovanni Battista Hospital, University of Torino, Torino, Italy.
- Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy.
- Gaetano Barresi Department of Human and Paediatric Pathology, Urology Section, University of Messina, Messina, Italy.
- S.H. Ho Urology Centre, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China
- Department of Radiation Oncology, University of California, Los Angeles, CA, USA
- Department of Urology, Mayo Clinic, Rochester, MN, USA