AUA, ASTRO issue new guidance on radiation after radical prostatectomy

So the American Urology Association (AUA) is clearly “on a roll” when it comes to guidance on the detection and management of prostate cancer. This is the third new guidance document issued in a matter of days.

This latest guidance document has been issued collaboratively by the AUA and the American Society for Radiation Oncology (ASTRO). It contains a series of nine very specific guideline statements, as follows:

Guideline Statement 1. Patients who are being considered for management of localized prostate cancer with radical prostatectomy should be informed of the potential for adverse pathologic findings that portend a higher risk of cancer recurrence and that these findings may suggest a potential benefit of additional therapy after surgery. (Clinical Principle)

Guideline Statement 2. Patients with adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extraprostatic 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 two randomized controlled trials that addressed these outcomes indicated a benefit but the other trial did not demonstrate a benefit. However, the other trial was not powered to test the benefit regarding metastases and overall survival. (Clinical Principle)

Guideline Statement 3. Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy including seminal vesicle invasion, positive surgical margins, or extraprostatic extension because of demonstrated reductions in biochemical recurrence, local recurrence, and clinical progression. (Standard; Evidence Strength: Grade A)

Guideline Statement 4. Patients should be informed that the development of a PSA recurrence after surgery is associated with a higher risk of development of metastatic prostate cancer or death from the disease. Congruent with this clinical principle, physicians should regularly monitor PSA after radical prostatectomy to enable early administration of salvage therapies if appropriate. (Clinical Principle)

Guideline Statement 5. Clinicians should define biochemical recurrence as a detectable or rising PSA value after surgery that is ≥ 0.2 ng/ml with a second confirmatory level ≥ 0.2 ng/ml. (Recommendation; Evidence Strength: Grade C)

Guideline Statement 6. A restaging evaluation in the patient with a PSA recurrence may be considered. (Option; Evidence Strength: Grade C)

Guideline Statement 7. Physicians should offer salvage radiotherapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease. (Recommendation; Evidence Strength: Grade C)

Guideline Statement 8. Patients should be informed that the effectiveness of radiotherapy for PSA recurrence is greatest when given at lower levels of PSA. (Clinical Principle)

Guideline Statement 9. Patients should be informed of the possible short-term and long-term urinary, bowel, and sexual side effects of radiotherapy as well as of the potential benefits of controlling disease recurrence. (Clinical Principle)

The following documents related to this new guideline are available on line:

There may be some considerable controversy about the interpretation of this new guideline. It is certainly the case that numerous men with “adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extraprostatic extension”at the time of surgery, and whose PSA level drops to an undetectable level post-surgery, have no rise in their PSA level after their surgery and appear to have been clinically cured of the original cancer. The question is therefore going to be exactly how individual surgeons apply some over the above guidance — i.e., by duly informing the patient but by adding “However, in your case I think we can afford to wait and monitor your PSA rather than applying radiation therapy immediately.”

The other issue that does not seem to be addressed in this guidance at all is the patient’s PSA doubling time. The situation of a man with a rising PSA post-surgery that goes from 0.1 to 0.4 over a period of 6 years (i.e., a PSA doubling time of 2 years) would seem to The “New” Prostate Cancer InfoLink to be very different to that of a man who’s PSA is doubling every 6 months or so and therefore goes from 0.1 to 0.4 in just 12 months. The former may never show signs of significant metastatic disease; the latter , on the other hand, probably will.

It is worth noting that in the detailed discussion of Guideline Statement 3 in the full text of the guideline, the authors wrote as follows:

The Panel is fully aware that the apparent benefits associated with ART are the result, in part, of a subset of patients treated who never would have presented with recurrence. For this reason, the Panel emphasizes that ART should be offered to all patients at high risk of recurrence because of adverse pathological features. 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). Whether ART is likely to benefit a particular patient and should be administered is a decision best made by the multi-disciplinary treatment team and the patient with full and thoughtful consideration of the patient’s history, current functional status, values, and preferences, and his tolerance for the potential toxicities and quality of life effects of RT.

4 Responses

  1. As a layperson, I understand the word “recommendation” to mean a directive to take or not take certain action. But the word “recommendation”, per the definitions, is used in the guidelines when the evidence grade is “C”, which means low quality and low certainty of evidence (which is hardly a “recommendation” as I would use the word). If the evidence grade is “A” or “B” (high quality and high certainty), that results in a “standard” (but which I would consider to be a “recommendation”). Guideline 3 states the physician should “offer” ART, and guideline 7 states the physician should also “offer” SRT. Both should be “offered”, even though guideline 3 is a “standard’ and guideline 7 is a “recommendation”. “Offered” does not mean to “recommend”.

    Am I correct to conclude that when each guideline is “offered” (i.e., “the patient, his family and the multi-disciplinary treatment team … [will] engage in [the] shared decision-making process in which the patient is advised to consider the possibility of additional treatment (i.e., RT).”), it is at that time when the physician will state to the patient, with respect to ART, “there is good evidence to support this treatment choice”, and with respect to SRT, “there is not very much evidence to support this treatment choice, and the evidence that there is, is not of good quality”? If so, isn’t the bottom line that the physician, following these guidelines, will always “offer” both but “recommend” ART over SRT in practice (or at least the patient would be imprudent to choose SRT because of the low evidence grade)? Help!

  2. Dear Richard:

    Clinical guidelines like this do not come in black and white. They always come in shades of grey. Furthermore, all guidelines are subject to the individual physician’s views on the degree of applicability of a particular guideline to a particular patient’s individual situation and the individual patient’s willingness to accept the “recommended” (or “offered”) form of care.

    Language is important in all of this, and rather than try to distinguish with precision between a “recommendation” and and “offer”, I believe it is better to look at all guidelines as “suggestions” that range in strength from being so strong that they might as well be considered to be absolute truths (e.g., a guideline that tells physicians and the parents of newborn children that all children should be vaccinated against polio) to being closer to “perhaps a good idea but we aren’t certain about it” (e.g., some of the guidelines you refer to above that come with only a “C” level of evidence).

    It is also important to understand that organizations that issue guidelines like this have limited power to enforce them on anyone (even their own members), so precisely how they get applied can vary considerably. There are plenty of well known examples of guidelines that are extremely strong that still aren’t universally adopted and applied by the medical community. One of these is the recommendation that anyone who had had a heart attack should subsequently receive treatment with a type of drug called an ACE inhibitor. This guideline comes with extremely good supporting evidence. ACE inhibitor therapy comes with a really rather low risk for side effects, and most ACE inhibitors are now generic, so there is no real cost issue. And yet large numbers of people (I think about 20% last time I heard) who have heart attacks are not put on ACE inhibitor therapy when they leave hospital despite considerable efforts by many organizations to get physicians to conform to this recommendation.

  3. What you state makes perfect sense and is very easy to understand. Seems like the guidelines would be easier to apply and comprehend if they used levels of “recommendations” (or “suggestions”), e.g., from highest to lowest, and they dispensed with the harder to distinguish “standard” from “recommendation” terms. Thanks for translating!!

  4. Regarding ART and SRT, a recent retrospective study published in the Journal of Urology (see “Identifying appropriate patients for early salvage radiotherapy after prostatectomy“) noted that:

    “[a] significant association between higher rPSA [relapsed PSA] values and PSA progression after SRT was identified in patients with GS 8-10, but not GS ≤7. In patients with GS 8-10, [freedom from PSA progression] at 53 months was 77% vs 26% when SRT was initiated at a rPSA of ≤0.33 ng/mL vs 0.34-1.0 ng/mL, respectively (log-rank p = 0.003).”

    The evidence seems to be growing that SRT when PSA is barely detectable can be as effective as ART. This could spare some folks whose PSA after surgery becomes undetectable from having to get radiation therapy until they see any PSA rise (using an ultrasensitive PSA test). In particular, those with Gleason 8-10 who have positive margins might want to wait, since nearly half of all positive margins prove non-viable.

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