After radical prostatectomy, adverse pathologic features and postoperative prostate-specific antigen (PSA) levels can herald disease recurrence or progression. Postoperative radiotherapy (RT) remains beneficial in this setting.

To examine the evidence supporting the use of postoperative RT as well as recent advances that help determine timing, scope, and use in combination with androgen deprivation therapy (ADT) with or without lymphatic irradiation.

A search was conducted of Medline (Ovid), Embase (Elsevier), and the Cochrane Library (Wiley) databases, in addition to clinical trial registries. The reference list of included studies was reviewed for relevant articles. The search was limited to studies published between January 1, 2014, and December 31, 2019.

After 548 citations were screened, 27 articles were selected for inclusion. In addition to conventional imaging, positron-emission tomographic (PET)-based radiotracers can aid in disease localization. While PET imaging may influence management with RT, studies are underway examining this issue, and several limitations must be considered, such as limited detectability at lower PSA levels and regional sensitivity. Available genomic classifiers can risk stratify patients or assess potential added benefit of RT. Prospective validation is underway with cooperative group trials. Adjuvant RT, on the basis of adverse pathologic features (such as extraprostatic extension or positive margins) is beneficial in terms of disease control, but it is unclear whether this therapy translates into more meaningful clinical benefit (eg, improved overall survival and a reduction in metastasis), which has been demonstrated by only 1 older, prospective randomized study. Preliminary data suggest that for a relatively favorable-risk population (low Gleason score but with positive margins), PSA monitoring may be a reasonable alternative in some men. Use of androgen deprivation therapy and lymphatic irradiation should be considered in higher-risk cohorts (those with high PSA, high Gleason score, seminal vesicle invasion or node positivity) in conjunction with postoperative RT.

The findings of this review suggest that postprostatectomy RT should be considered for men with prostate cancer in the setting of adverse pathologic features; in carefully selected patients with favorable characteristics, close PSA monitoring is an option. Androgen deprivation therapy and pelvic lymphatic irradiation should be considered for higher risk cohorts (eg, higher PSA values, higher Gleason score). PET imaging and molecular studies remain unproven as decision tools.