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Assessment of Postprostatectomy Radiotherapy as Adjuvant or Salvage Therapy in Patients With Prostate CancerA Systematic Review

Educational Objective
To learn the role of postprostatectomy radiotherapy for adjuvant or salvage therapy.
1 Credit CME
Key Points

Question  Can advances in postprostatectomy radiotherapy in men with prostate cancer help guide its optimal timing, scope, and use in combination with androgen deprivation therapy?

Findings  This review evaluates 27 studies on postprostatectomy radiotherapy delivered as adjuvant therapy or as salvage in the setting of persistent or increasing prostate-specific antigen levels in men with prostate cancer. Preliminarily, for certain lower-risk patients, close prostate-specific antigen level monitoring may be sufficient to guide initiation of salvage therapy; newer molecular imaging and genomic classifiers are thus far unproven tools to aid in decision-making.

Meaning  Postprostatectomy radiotherapy for men with prostate cancer appears to be a modality appropriate in the setting of adverse pathologic features or in the salvage setting with close prostate-specific antigen level monitoring.

Abstract

Importance  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.

Objective  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.

Evidence Review  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.

Findings  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.

Conclusions and Relevance  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.

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Article Information

Accepted for Publication: May 19, 2020.

Corresponding Author: Maha Hussain, MD, Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, 303 E Superior St, Ste 3-107, Chicago, IL 60611 (maha.hussain@northwestern.edu).

Published Online: August 27, 2020. doi:10.1001/jamaoncol.2020.2832

Author Contributions: Drs Sachdev and Hussain had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sachdev, Carroll, Sandler, Wafford, Auffenberg, Roach, Evans, Hussain.

Acquisition, analysis, or interpretation of data: Sachdev, Carroll, Nguyen, Schaeffer, Roach, Evans, Hussain.

Drafting of the manuscript: Sachdev, Carroll, Roach, Evans, Hussain.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Sachdev, Carroll, Wafford, Schaeffer, Roach.

Supervision: Sachdev, Carroll, Sandler, Nguyen, Schaeffer, Evans, Hussain.

Conflict of Interest Disclosures: Dr Carroll reported serving as a paid member on the advisory boards of Insightec (tissue ablation), Nutcracker Therapeutics (mRNA), and Francis Medical (tissue ablation). Dr Sandler reported receiving personal fees from Janssen and holding stock in Radiogel outside the submitted work; and being an unpaid member of the American Society for Radiation Oncology Board of Directors. Dr Nguyen reported receiving grants and personal fees from Janssen, Astellas, and Bayer; and personal fees from Ferring, Cota, Blue Earth, Dendreon, Boston Scientific, and Augmeni outside the submitted work. Dr Hussain reported receiving grants and personal fees from Pfizer, AstraZeneca, Genentech, and Bayer; and personal fees from Astellas, Sanofi/Genzyme, and Daiichi Sankyo outside the submitted work. No other disclosures were reported.

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