PSA recurrence after radiation therapy is defined in several ways. The RTOG-ASTRO Phoenix Consensus Definition is a PSA increase by 2 ng/mL or more after the PSA nadir, however, many clinicians do not wait for the Phoenix criteria to be achieved before evaluating recurrence. The NCCN guidelines suggest that a recurrence evaluation should be considered when PSA has been confirmed to be increasing after radiation even if the increase above nadir is not yet at 2 ng/mL, especially in candidates for salvage local therapy who are young and healthy.
According to Dr. Feng, the management of a PSA recurrence after definitive radiation therapy includes the initial workup (imaging with a potential biopsy), local therapy for local recurrences, local therapy for regional or distant recurrences, and systemic therapy. In this particular talk, Dr. Feng focused on the workup and treatment of local recurrences.
The significance of a local recurrence after radiation therapy was recently evaluated by the MSKCC group and published in the Journal of Urology.1 In this study, 382 patients underwent a posttreatment biopsy after external beam radiotherapy for clinically localized prostate cancer. The prevalence of positive biopsy was 30%, the treatment effect was 22%, and a negative biopsy was 48%. Importantly, the 15-year PSA relapse rate associated with a negative biopsy was 34%, the treatment effect was 36%, and positive post-treatment biopsy was 79%. The risk of distant metastasis was 2.6-fold higher in patients with a positive biopsy and cause-specific mortality was twice as high in patients with a positive biopsy compared to those with negative biopsy/ treatment effect biopsy.
Dr. Feng’s personal criteria for who is an ideal candidate for local therapy after radiation therapy failure are as follows:
- Original clinical stage T1-2, NX or N0
- Life expectancy >10 years
- PSA now <10 ng/mL
- Long interval to recurrence (> 3 years)
- Long PSA doubling time (>12 months)
- Organ-confined at recurrence (assessed by ie. MRI)
- 38% for <0.5 ng/mL (n = 136)
- 57% for 0.5 to <1.0 ng/mL (n = 79)
- 84% for 1.0 to <2.0 ng/mL (n = 89)
- 86% for 2.0 to <5.0 ng/mL (n = 158)
- 97% for ≥5.0 ng/mL (n = 173)
In summary of the above, Dr. Feng highlighted his management of a PSA recurrence after definitive radiation therapy with the following algorithm:
According to Dr. Feng, there is a “potpourri of options” for local therapy in this setting, including brachytherapy, salvage radical prostatectomy, HIFU, cryotherapy, and SBRT. He notes that almost all of the salvage therapies for post-radiation therapy local recurrence are retrospective in nature.
Dr. Feng concluded his presentation with the following take-home messages:
- There is a significant subset of prostate cancer patients with PSA recurrence after definitive radiation therapy.
- Positive posttreatment biopsies are associated with metastatic progression.
- Advanced imaging approaches allows detection of recurrences at PSA levels lower than the nadir +2 (Phoenix criteria) definition.
- Treatment approaches for biopsy-proven local recurrences (in the absence of metastases) include salvage brachytherapy, radical prostatectomy, HIFU and cryotherapy.
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 Advanced Prostate Cancer Consensus Conference (APCCC) #APCCC19, Aug 29 - 31, 2019 in Basel, Switzerland
- Zelefsky MJ, Goldman DA, Reuter V, et al. Long-term Implications of a Positive Posttreatment Biopsy in Patients Treated with External Beam Radiotherapy for Clinically Localized Prostate Cancer. J Urol 2019 Jun;201(6):1127-1133.
- Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol 2019 Jun 1;5(6):856-863.