Editing Prostate Cancer: Management of Locally Advanced Prostate Cancer (section)

===== Evidence =====

*'''ARTISTIC Meta-analysis'''
** Included 2153 patients from RADICALS, GETUG-17 and RAVES trials which evaluated adjuvant radiation therapy vs. surveillance with early salvage radiation therapy for PSA increase in patients with high-risk localized prostate cancer following radical prostatectomy.
***Criteria for early salvage therapy was a PSA >0.1 ng/mL or >0.2 ng/mL depending on the trial
***The proportion of patients in the early salvage therapy groups that received radiation therapy ranged from one third to one half.
** '''Results'''
*** '''No difference in event-free survival''' based on meta-analysis of 3 trials (pooled HR 0.95, 95% CI 0.75 to 1.21)
***'''Adjuvant radiation was associated with increased risk of genitourinary toxicity'''
*** '''Overall, there were few patients with high-risk features'''
** [https://pubmed.ncbi.nlm.nih.gov/33002431/ Vale, Claire L., et al.]" Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data." ''The Lancet'' (2020).
**'''RADICALS'''
*** 1,396 males from multiple countries that underwent prostatectomy for non-metastatic prostate cancer with undetectable PSA and ≥1 risk factor:
**** pT stage ≥3
**** Grade group ≥2
**** Positive margins
**** Preoperative PSA ≥ 10 ng/mL
*** Randomized to adjuvant radiation vs. early salvage (with second randomization on duration of ADT 6 vs. 24 months)
**** Salvage radiation administered for PSA biochemical progression, defined as either:
***** 2 consecutive rising PSA amounts with a PSA > 0.1 ng/mL
***** 3 consecutive rising PSA
*** Outcomes:
**** Primary: distant metastasis-free survival (though initially was disease-specific survival)
**** Secondary: disease-specific survival, overall survival, initiation of non-protocol hormone therapy, treatment toxicity, and patient-reported outcomes.
*** Results:
**** Median follow-up: 5 years
**** Distant metastasis-free survival outcome data not mature
**** No significant difference in biochemical progression-free survival (85% radiation vs. 88% salvage at 5-years (HR 1.10, 95% CI 0.81-1.49))
*** Parker, Christopher C., et al."Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial." ''The Lancet'' 396.10260 (2020): 1413-1421.
** '''GETUG-17'''
*** The French Groupe d’Étude des Tumeurs Uro-Génitales (GETUG-17) trial will evaluate a similar patient population but will randomize patients to immediate adjuvant radiation therapy versus observation patients and treating with salvage radiation when PSA levels reach a level of 0.2 ng/mL.
** '''RAVES''': Radiotherapy—Adjuvant versus Early Salvage trial
*** A phase III trial randomizing patients with pathologic T3 disease and/or positive margins. Primary end point is biochemical cancer control with secondary outcomes including quality of life, toxicity, anxiety/depression, biochemical failure–free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, time to initiation of androgen ablation, quality adjusted life years, and cost-utility.
*** Trial terminated due to poor accrual