Editing Adjuvant and Salvage Radiotherapy After Prostatectomy (2019) (section)

== Salvage Radiotherapy ==

* '''At the time of guideline publication, no RCTs directly comparing SRT to ART; evidence limited to observational studies'''
* '''Patients should be informed that the development of a PSA recurrence after surgery is associated with a higher risk of development of metastasis or death from prostate cancer. PSA monitoring after radical prostatectomy should be done regularly to enable early administration of salvage therapies if appropriate.'''
** Pound et al. were among the first to describe the time course of disease progression. They followed 1997 consecutive men undergoing RP at the Johns Hopkins Hospital and demonstrated that no man experienced either distant or local recurrence without also demonstrating a rising PSA level. Among 304 men who developed detectable PSA values following surgery, the median time to the development of metastases was 8 years. Men who developed metastatic disease usually died at median 5 years later. The median PSADT provided the most statistically significant prediction of time to distant progression. Men with a PSADT < 10 months usually developed metastases within 5 years of surgery, while men with a PSADT > 10 months developed metastases much later.
** '''Men with an increasing PSA after surgery are at risk for developing metastases and subsequently dying from their disease; this risk is particularly high among men with rapid PSADT.'''
* '''Biochemical recurrence is defined as a detectable or rising PSA value after surgery that is ≥ 0.2 ng/ml with a second confirmatory level ≥ 0.2 ng/ml.'''
** '''No evidence to suggest a threshold above which RT is ineffective'''
** Data from retrospective and prospective trials suggest that '''more favorable biochemical outcomes are associated with very low PSA values at the time RT is offered'''.
** A small percentage of patients may have detectable but stable PSAs for ≥10 years without evidence of clinical failure, which may reflect the presence of benign prostate glands in the surgical bed.
** Calculation of PSADT using data derived from ultra-sensitive assays may yield markedly different PSADT values compared to using data derived from higher-threshold assays; how these differences should be interpreted is unclear. Given the lack of evidence regarding the use of ultrasensitive PSA assays to guide care, the Panel judged that the use of the 0.2 ng/ml threshold value with a second confirmatory value to document recurrence is the optimal strategy currently.
* '''A restaging evaluation in the patient with a PSA recurrence may be considered'''
** '''In the patient with evidence of recurrence manifested as a detectable or rising PSA, determining the site of recurrence (local v. metastatic) may be relevant to select an appropriate salvage strategy.'''
** '''Local recurrence'''
*** '''Overall, MRI yielded the highest and most consistent sensitivities and specificities for the detection of local recurrence.'''
*** Other modalities (TRUS, DRE, PET/CT) exhibited excellent sensitivity but poor or variable specificity or vice versa.
** Recurrence in nodes
*** Insufficient data are available to recommend a specific technique
** '''Recurrence in bone'''
*** '''Yield of bone scan is extremely low in patients with PSA < 10 ng/ml;''' at PSA levels < 10 ng/ml, less than 5% of patients had a positive bone scan; given that most patients manifest biochemical failure at PSA values <1.0 ng/ml, the yield of bone scans will be low.
** Metastatic recurrence.
*** Definitive conclusions regarding the best imaging strategy to detect metastatic recurrence are not possible, but data suggest that 11C-choline PET/CT, 18FDG PET and 18FCH PET/CT are promising.
** Recurrence at all sites
*** 11C-choline PET/CT appears promising; the probability of a positive scan, however, may depend on PSA level and PSA dynamics
* '''SRT should be offered to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease'''
** SWOG 8794 and EORTC 22911 included a subgroup of patients who had detectable PSA levels post-RP patients that could be categorized as salvage patients. Salvage RT in these patients was associated with reduced metastatic recurrence and biochemical failure
** Some observational studies suggest a cancer-specific and overall survival benefit
* '''The effectiveness of SRT for PSA recurrence is greatest when given at lower levels of PSA'''
** '''No evidence to suggest a threshold above which RT is ineffective'''
** If recurrence is detected without evidence of distant metastases, SRT should be administered at the earliest sign of PSA recurrence and, ideally, before PSA rises to 1.0 ng/ml.
* '''Clinicians should offer hormone therapy to patients treated with SRT (postoperative PSA ≥0.2 ng/mL).''' Ongoing research may someday allow personalized selection of hormone or other therapies within patient subsets
** 2 RCTs (RTOG 9601175 and GETUG-AFU 16176) evaluated the effects of hormone therapy on OS, and on biochemical and clinical progression among patients who received SRT after prostatectomy. The type and duration of hormone therapy was different between trials. Both trials demonstrated improved PFS while RTOG 9601 also found improved OS.
** Based on findings from these 2 RCTs, the Panel recommends that clinicians offer hormone therapy to candidates for SRT, namely patients with postoperative PSA ≥0.2 ng/mL and no distant metastasis. There is insufficient evidence for such in patients with lower (<0.2 ng/mL) PSA levels. When offered, the clinician must provide information about potential benefits and harms
** Upcoming trials evaluating hormonal therapy: RTOG 0534 (SRT), RADICALS (ART and SRT)