Trends raise post-RP RT guide’s relevance

In May 2013, the American Urological Association (AUA) and the American Society for Radiation Oncology (ASTRO) released a joint guideline for radiotherapy after prostatectomy (J Urol 2013; 190:441-9). As a framework for practitioners caring for men who undergo surgery for treatment of prostate cancer, the evidence-based guideline contains nine statements that address use of adjuvant and salvage radiotherapy, conduct of a restaging evaluation, patient counseling, and a definition for biochemical recurrence (table).

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In November 2014, and after conducting an updated literature search, a panel from the American Society of Clinical Oncology (ASCO) published an endorsement of the AUA/ASTRO radiotherapy guideline (J Clin Oncol 2014; 32:3892-8). In their report, the ASCO endorsement panel stated the AUA/ASTRO guidelines were “clear, thorough, and based on the most relevant scientific evidence,” but they included some qualifying statements further underscoring the importance of informed shared decision-making as well as taking into account that the risk-benefit ratio of radiotherapy after prostatectomy differs among individuals.

Today and into the near future, urologists are likely to be encountering a growing population of men for whom adjuvant or salvage radiotherapy after prostatectomy is a relevant consideration.

Whereas historically, about one-half of men diagnosed with prostate cancer undergo prostatectomy, about one-third of those patients might be considered candidates for adjuvant radiation based on risk stratification, and about one-third of men develop a recurrence within a decade after prostatectomy, the landscape is changing.

An increasing number of studies investigating the impact of the 2012 U.S. Preventive Services Task Force recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer have documented a shift toward the diagnosis of higher risk prostate cancers. Increased acceptance of the recommendation for active surveillance by men with low-grade, low-stage tumors is also contributing to an increase in patients who have higher risk disease at the time of prostatectomy.

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Considering these trends, the importance of practitioners becoming familiar with the content of the AUA/ASTRO guideline and ASCO endorsement is heightened.

Next: Guideline development

Guideline development

Ian M. Thompson, Jr., MD, served as co-chair for the AUA/ASTRO guideline on behalf of the AUA.

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Dr. Thompson said that to his knowledge, the guideline on radiotherapy after radical prostatectomy stands out as the first time the AUA has undertaken joint development of a guideline for an oncologic indication.

Dr. Thompson“All AUA guideline panels for prostate cancer have been multidisciplinary. This guideline, was different, however, because AUA and ASTRO came together to select the panel chairs and additional members, and the final document has been vetted extremely well by members of both organizations,” said Dr. Thompson, director of the Cancer Therapy and Research Center and Glenda and Gary Woods Distinguished Chair in genitourinary oncology at the University of Texas Health Science Center, San Antonio.

Dr. Thompson also underscored that the development process was scientifically rigorous and onerous, considering the volume and granularity of the data scrutinized by the guideline committee members.

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“The panel considered the quality of the evidence along with the impact of radiotherapy on different disease-specific outcomes, quality of life, and its side effects, and then had to reach consensus and craft concise statements that would provide clinicians guidance on patient management,” Dr. Thompson told Urology Times.

 Next: Take-home messages

Take-home messages

Dr. Thompson said that from a practical standpoint, the key messages for urologists can be summarized as follows:

• In the initial discussion about treatment for patients with prostate cancer and taking into account risk stratification, the conversation should explain that management with surgery might include adjuvant radiotherapy post-prostatectomy.

• When the post-prostatectomy pathology report indicates high-risk disease, there is an obligation to inform the patient about adjuvant radiotherapy.

• Similarly, for a patient who has a detectable or rising PSA post-prostatectomy, the clinician has an obligation to inform the patient about salvage radiotherapy.

• These conversations need to include discussion of the potential risks and benefits of radiotherapy so that the patient will have sufficient information to make an informed decision.

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“Although I do not know the exact extent to which these discussions are taking place, there is evidence that they are not happening consistently and there is room for improvement in all of these areas,” said Dr. Thompson.

Since details on risks and benefits are not contained in the nine guideline statements, it is important that physicians read the document in its entirety, according to Dr. Thompson.

“Just like for everything else in medicine, providers must have the proper background knowledge so that they can explain and help the patient in front of them understand the nuances of management options,” he said.

For example, the guideline states that physicians should offer salvage radiation therapy to patients with a PSA recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease. It defines PSA recurrence as a detectable or rising PSA value of ≥0.2 ng/mL on two occasions using a standard PSA assay that registers at 0.1 ng/mL. However, the decision to initiate salvage therapy for such a patient should take into account the individual’s pathology findings and other risk factors and clinical features, along with the patient’s preferences and values.

“A younger patient with extensive high-grade disease and seminal vesicle invasion who has a detectable PSA at 3 months post-prostatectomy represents a different situation than an older man with comorbidities who has detectable PSA 8 years after surgery and perhaps has a contraindication to radiotherapy, such as ulcerative colitis,” Dr. Thompson explained.

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“So it is important that as clinicians think about biochemical recurrence, they don’t just consider the PSA level in a vacuum. Rather, they need to take into account when it was first detected, the rise, the original tumor’s malignant potential, and the potential risks and benefits of salvage therapy for the individual.”

Next: Enriched interpretations

Enriched interpretations

Stephen J. Freedland, MD, served as lead author of the ASCO endorsement of the AUA/ASTRO guideline. The information it contains aims to help physicians identify patients who are most likely to benefit from radiotherapy and emphasizes the importance of conducting a full discussion of the benefits and risks to enable shared decision-making.

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“Being the second to market, so to speak, the ASCO endorsement panel could see what was in the AUA/ASTRO guideline and qualify the statements to emphasize these concepts,” said Dr. Freedland, director of the Center for Integrated Research in Cancer and Lifestyle and Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai Medical Center, Los Angeles.

One issue addressed by the ASCO endorsement is use of the word “offer” in the statements about presenting adjuvant or salvage radiotherapy.

“We felt that ‘offer’ simply means making the treatment available. Therefore, we provided a clearer interpretation that recognizes shared decision-making requires a thorough discussion with the patient about risks and benefits, consideration of the individual’s risk for recurrence or progression, and weighing the potential benefit against the known risks for that patient,” Dr. Freedland said.

Recognizing that the greatest benefit of adjuvant radiation treatment would extend to men who are most likely to develop a recurrence, the ASCO endorsement also clarified who is at highest risk. The AUA/ASTRO guideline states that patients with adverse pathologic findings at prostatectomy, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, should be offered adjuvant radiotherapy. The ASCO endorsement refined the criteria, and identified men with Gleason score 8 to 10, seminal vesicle invasion, extensive positive margins, and elevated postoperative PSA as likely to derive the greatest benefit in terms of absolute risk reduction from adjuvant radiotherapy.

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“The AUA/ASTRO guideline statement implies that all patients with adverse pathologic findings at prostatectomy are the same, but they are a heterogeneous group. Based on information in the literature and to a certain degree, expert opinion, we better defined those at highest risk,” Dr. Freedland said.

Next: What's ahead

What’s ahead

Looking at population-level data, Dr. Freedland observed that use of adjuvant radiation after prostatectomy is quite low. As he believes that represents underutilization and considering that adjuvant radiation is overutilized in some patients, albeit a much smaller group, Dr. Freedland hopes those patterns might be changed for the better by the AUA/ASTRO guideline.

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In terms of guideline updates, both Dr. Freedland and Dr. Thompson expect that recommendations about a role of radiotherapy after prostatectomy will most likely be impacted by the availability of results from clinical trials evaluating a role for medical therapies.

Dr. Freedland is also looking to studies investigating molecular markers and refining clinical and pathologic criteria for risk stratification that will help to better define who stands to benefit most from adjuvant therapy after prostatectomy.

“Radiation is not inherently evil or good,” he said. “It can be lifesaving in the right patient and cause horrible complications in the wrong patient. Like everything we do in medicine, a decision on adjuvant radiotherapy for a particular patient needs to be based on defining that individual’s risk-benefit ratio.”

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