Adjuvant and Salvage Radiotherapy After Prostatectomy (2019)

See Original Guideline

Definitions

• Adjuvant radiotherapy (ART): administration of RT to post-radical prostatectomy (RP) patients at a higher risk of recurrence because of adverse pathological features prior to evidence of disease recurrence (i.e., with an undetectable PSA)
• Salvage radiotherapy (SRT): administration of RT to the prostatic bed and possibly to the surrounding tissues, including lymph nodes, in the patient with PSA recurrence after surgery but no evidence of distant metastatic disease
  • Biochemical recurrence after surgery is defined as a detectable PSA level > 0.2 ng/mL with a second confirmatory level > 0.2 ng/mL.

• Patients with adverse pathology detected at prostatectomy who have a persistent post-prostatectomy PSA level should be offered post-RP SRT (not technically adjuvant since no period without disease) [source?]

ART vs. SRT

• Advantages/disadvantages
  • Overtreatment with ART: ART may involve irradiation of some patients who never would have had recurrent cancer, thus exposing them unnecessarily to the risks, toxicity, and QoL impact of RT. SRT avoids overtreatment.
  • Delayed treatment with SRT: waiting to administer RT as a salvage therapy could be less effective, particularly in patients with high-risk disease, and could allow the progression to metastatic disease.
    • Observational studies suggest that ART patients generally have better outcomes compared to SRT patients. However, this is difficult to compare these groups that SRT studies focus only on patients who have already relapsed and the ART group has patients that were never destined to recur
    • No published trials comparing ART to SRT
      • Pending publication: RADICALS
• [At the time of guideline publication,] insufficient evidence to determine superiority of ART vs. SRT

ART

• Patients who undergo RP for localized prostate cancer should be informed of the potential for adverse pathologic findings that increase risk of cancer recurrence and that these findings may suggest a potential benefit of additional therapy after surgery.
  • The first PSA generally should be obtained 2-3 months post-RP
  • Recurrence after RP is thought to result from residual subclinical disease in the operative site or occult metastatic disease that was present at the time of the prostatectomy
  • The risk of recurrence is greater among men with adverse pathology, such as positive surgical margins, seminal vesicle invasion, extraprostatic extension, and higher Gleason scores
  • Rates of recurrence in post-RP patients with adverse pathological features may be > 60% at 5 years post-RP
• ART should be offered to patients with adverse pathologic findings (seminal vesicle invasion, positive surgical margins, or extraprostatic extension) at prostatectomy
  • 3 RCTs (SWOG 8794, EORTC 22911, and ARO 96-02) randomized patients with adverse pathological features at prostatectomy to ART vs. observation
    • See Management of Locally Advanced Prostate Cancer Notes
    • All 3 trials have > 10 years follow-up
    • All 3 trials documented significant improvements in biochemical RFS with use of ART.
      • The Panel notes that prevention of biochemical progression is an important clinical endpoint because biochemical progression may trigger salvage therapy (i.e., hormone therapy), with its associated toxicities (increased risks for osteoporosis, cardiovascular disease and other health problems with ADT) and QoL impact. In addition, patients with biochemical recurrence are more likely to manifest metastatic recurrence. Therapies for metastatic recurrence, such as hormone therapies, can also have profound QoL impact.
    • The 2 RCTs that evaluated locoregional failure (SWOG 8794; EORTC 22911) demonstrated a reduction in locoregional failure with ART
    • Both SWOG 8794 and EORTC 22911 reported statistically significant reductions in the use of subsequent salvage therapies with ART
    • SWOG 8794 and EORTC 22911 demonstrated improved cPFS (defined as clinical or imaging evidence of recurrence or death but not including biochemical progression) with ART
    • 2 of the trials, SWOG 8794 and EORTC 22911, assessed metastatic recurrence and OS. Only SWOG 8794 demonstrated significantly improved metastatic recurrence-free survival and overall survival; ARO-96-02 and EORTC were not designed to identify a significant reduction in metastasis or death with adjuvant radiotherapy
      • Given the consistency of findings across trials regarding other clinically-important endpoints of reduced biochemical and locoregional failure, clinical progression, and the reduction in the need for initiation of salvage therapies in patients administered ART, the Panel concluded that patients with high-risk pathological features should be offered ART.
        • By “offered,” the Panel means that the patient, his family and the multi-disciplinary treatment team should engage in a shared decision-making process in which the patient is advised to consider the possibility of additional treatment (i.e. RT).
      • Patients with adverse pathologic findings should be informed that compared to RP only, ART:
        • Reduces the risk of biochemical recurrence, local recurrence, and clinical progression of cancer
        • Impact on subsequent metastases and overall survival is less clear
      • ART is usually administered within 4-6 months following RP, generally after the return of acceptable urinary control
        • As sexual function can require 1-2 years before a full return of function is observed, return of erections is not a requirement before initiation of adjuvant radiation.
      • The role of hormone therapy in addition to ART remains uncertain
        • This will be addressed in the RADICALS trial