Editing Biochemical Recurrence (section)

=== Local failure ===
* '''Salvage Radiation'''
** '''See Management of Locally Advanced Prostate Cancer Chapter Notes'''
** '''Radiation is considered ‘salvage’ in the context of persistent or rising PSA level after radical prostatectomy'''
***'''Radiation is considered ‘adjuvant’ in the context of undetectable PSA level after radical prostatectomy'''
** '''Improves biochemical recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival'''
*** '''Of all salvage options, including ADT, radiation provides the best long-term progression-free survival.'''
** Whole-pelvis vs. prostatic bed radiation therapy
*** No mature randomized controlled trial demonstrates the added benefit of whole-pelvis radiation compared to prostatic bed only radiation
*** RTOG 0534
**** RCT currently accruing patients with high-risk prostate cancer features on radical prostatectomy and with post-surgery PSA levels of 0.1 ng/mL or greater to < 2.0 ng/mL
**** Randomizing them to prostatic bed radiation alone, prostatic bed radiation + 6 months ADT, and prostatic bed radiation therapy plus pelvic lymph node radiation therapy + 6 months ADT
** Timing
*** Outcomes improved when delivered at lower PSA values, some use ≤ 0.5 ng/mL
** '''Dosage of salvage radiation'''
*** '''At least 64 Gy of salvage radiation should be administered to the prostatic bed'''. However, emerging evidence now demonstrates improvement with higher dosages.
**** '''Recall EBRT radiation dose for localized disease: 76-80 Gy'''
**** '''Recall brachytherapy radiation dose for localized disease: ≈145 Gy for iodine and 125 Gy for palladium'''
** '''Concurrent Androgen Deprivation Therapy with Salvage Radiation'''
*** Theoretically, the use of systemic therapy with androgen deprivation may treat micrometastatic disease, shrink tumor burden making it more amenable to local salvage therapy, and potentially work in synergy with radiation therapy to treat remaining cancer cells.
*** '''Guidline Statement 9 from the 2017 AUA Adjuvant and Salvage Radiotherapy after Prostatectomy Guidelines: "Clinicians should offer hormone therapy to patients treated with salvage radiotherapy''' (postoperative PSA ≥0.2 ng/mL). Ongoing research may someday allow personalized selection of hormone or other therapies within patient subsets. (Standard; Evidence Strength: Grade A)"
*** '''GETUG-AFU 16'''
**** Population: 743 patients who underwent prostatectomy and whose prostate-specific antigen (PSA) increased from 0.1 ng/mL to between 0.2 ng/mL and 2.0 ng/mL
**** Randomized to radiotherapy +/- ADT (on first day of irridiation and 3 months later)
**** Primary outcome: progression-free survival
**** Results
***** Median follow-up: 112 months
***** Progression free-survival signficantly improved with addition of ADT (absolute benefit 15% at 10-years (65% radiation + ADT vs. 49% radiation alone)
**** Carrie, Christian, et al."Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial." ''The Lancet Oncology'' 20.12 (2019): 1740-1749.
*** '''RTOG 96-01'''
**** '''Population: 760 patients who underwent prostatectomy and were found to have pT3N0M0 or pT2 with positive margins and detectable PSA'''
**** '''Randomized to salvage radiation therapy +/- 2 years of bicalutamide'''
**** '''Results:'''
***** '''Median follow-up was 13 years'''
***** '''Bicalutamide had significantly improved OS, cancer-specific survival, and metastasis-free survival'''
***** '''Gynecomastia was significantly more common in the bicalutamide group'''
**** Shipley, William U., et al."Radiation with or without antiandrogen therapy in recurrent prostate cancer." New England Journal of Medicine 376.5 (2017): 417-428.
*** Observational study found that ADT most beneficial in patients with high-risk features§
*** Secondary analysis of RTOG 96-01 found that benefit of ADT was in those with PSA >0.60§
** '''Prognosis'''
*** '''Patients most likely to have favorable responses to salvage radiotherapy are those with'''
***# '''PSA recurrence long after surgery'''
***# '''Slowly rising PSA'''
***# '''Low-grade tumor'''
***# '''No seminal vesicle invasion'''
***# '''No lymph node metastases'''
*** Risk factors for biochemical relapse after salvage radiation include pathologic stage T3a or less versus T3b, pathologic Gleason score, and pre-salvage radiation PSA levels.
*** Patients with a PSA nadir > 0.05 ng/mL after salvage radiation therapy have an increased risk for distant metastatic disease and reduced prostate cancer–specific survival.
** '''Failure after salvage radiation therapy can be due to:'''
**# '''Persistent local disease'''
**# '''Recurrence of local disease'''
**# '''Persistence of metastasis'''
**# '''Development of metastatic disease'''