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Amendments to post prostatectomy radiation-therapy treatment guidelines

RadiationClinical guidance for radiation therapy after prostatectomy has been was amended by the American Society for Radiation Oncology.

Guideline Statement 2 was modified to account for the latest data from three randomized controlled trials evaluating the use of adjuvant radiotherapy, including new long-term data from the ARO 96-02 trial, which was incorporated to update the existing evidence base.

Statement 2: Patients with adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extra-prostatic extension should be informed that adjuvant radiotherapy, compared to radical prostatectomy only, reduces the risk of biochemical (PSA) recurrence, local recurrence, and clinical progression of cancer. They should also be informed that the impact of adjuvant radiotherapy on subsequent metastases and overall survival is less clear; one of three randomized controlled trials addressing these outcomes indicated a benefit, but the other two trials did not demonstrate a benefit. However, these two trials were not designed to identify a significant reduction in metastasis or death with adjuvant radiotherapy.

Guideline Statement 9 is a new guideline statement written to include outcome data from two randomised controlled trials (RTOG 9601 and GETUG-AFU 16), which evaluate the effects of hormonal therapy on overall survival, and on biochemical and clinical progression among patients who received salvage radiotherapy after prostatectomy. Based on findings from these randomised controlled trials, it was concluded there was sufficiently strong evidence overall to encourage hormonal therapy to be offered to patients who are candidates for salvage radiotherapy. When offered, the clinician must provide information about benefits and harms associated with this therapy, particularly discussing the improved freedom from disease progression documented in both trials, and improved overall survival as reported in RTOG 9601.

Statement 9: Clinicians should offer hormonal therapy with radiotherapy to patients who are candidates for salvage radiation therapy. Ongoing research may someday allow personalized selection of hormonal or other therapies within patient subsets.
In addition to the guideline statements, new information related to genomic classifiers, as predictors of treatment effectiveness, was added to the guideline future research needs. Further study in this area is needed to determine whether a genomic classifier is predictive of outcomes in a yet to be treated patient, and whether it is predictive for efficacy of a particular treatment.

"Evidence from three, well-established randomised trials now confirm significant improvements in biochemical recurrence-free survival among patients with adverse pathological features with the use of adjuvant radiotherapy," said Dr Ian Thompson, co-chair of the guideline panel and professor and chairman of the urology division at the University of Texas Health Sciences Centre at San Antonio, Texas. "Our expectation is this guideline is fully aligned to the latest science and provides physicians with a relevant blueprint for the use of radiotherapy after prostatectomy."

"As research in prostate cancer evolves and improves, data continue to accumulate in support of radiotherapy following radical prostatectomy. We now know that radiotherapy and the combination of hormone therapy with radiation, following radical prostatectomy, have contributed to even more favourable outcomes for patients than seen previously," said Dr Richard K Valicenti, co-chair of the guideline panel and professor and chairman of radiation oncology at the University of California-Davis Comprehensive Cancer Centre in Sacramento, California. "With the current update, this collaborative guideline now reflects nearly three decades of multidisciplinary research."

Abstract
Purpose: The purpose of this amendment is to incorporate newly-published literature into the original ASTRO/AUA Adjuvant and Salvage Radiotherapy after Prostatectomy Guideline and to provide an updated clinical framework for clinicians.
Materials and Methods: The original systematic review yielded 294 studies published between January 1990 and December 2012. In April 2018, the guideline underwent an amendment and incorporated 155 references that were published from January 1990 through December 2017. Two new key questions were added. One on the use of genomic classifiers and the other on the treatment of oligo-metastases with radiation post-radical prostatectomy.
Results: A new statement on the use of hormone therapy with salvage radiotherapy after radical prostatectomy was added and long-term data was used to update an existing statement on adjuvant radiotherapy. The balance of the guideline statements were re-affirmed and references were added to the existing literature base. A discussion on the use of genomic classifiers as a risk stratification tool was added to the future research discussion. No relevant data on oligo-metastases was found.
Conclusions: Hormone therapy should be offered to patients who have had radical prostatectomy and who are candidates for salvage radiotherapy. The clinician should discuss possible short- and long-term side effects with the patient as well as the potential benefits of preventing recurrence. The decision to use hormone therapy should be made by the patient and a multi-disciplinary team of providers with full consideration of the patient’s history, values, preferences, quality of life, and functional status.

Authors
Thomas M Pisansky, Ian M Thompson, Richard K Valicenti, Anthony V D’Amico, Shalini Selvarajah

[link url="https://www.sciencedaily.com/releases/2019/05/190501114337.htm"]American Society for Radiation Oncology material[/link]
[link url="https://www.practicalradonc.org/article/S1879-8500(19)30120-1/pdf"]Practical Radiation Oncology abstract[/link]

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