NCCN guidance on the initial management of low-risk, localized prostate cancer

As many readers will already be aware, the National Comprehensive Cancer Network (NCCN) has recently removed the word “preferred” from its statement regarding the use of active surveillance (AS) as an appropriate form of management of men with low-risk forms of localized prostate cancer. A broad swath of specialists in the initial management of low-risk disease, as well as many in the patient advocacy community, have been highly critical of this change to the NCCN guidelines.

Active Surveillance Patients International (ASPI), ZERO — The End of Cancer, and AnCan have all, already, written to the Chairman of the NCCN guidelines on the management of prostate cancer and protested NCCN’s recent decision.

Prostate Cancer International and The “New” Prostate Cancer InfoLink wish to make it very clear that we find this modification to the NCCN guideline to be utterly unjustifiable. It goes against common sense and it is clearly not supported by any available high-quality data. Indeed, Prostate Cancer International believes that the appropriate guidance for the management of favorable-risk forms of localized prostate cancer should state that:

  • For men with very low-risk disease, active surveillance is strongly recommended.
  • For men with low-risk disease, active surveillance is recommended.
  • For selected men with favorable, intermediate-risk disease, active surveillance is a reasonable option.

Furthermore, we would note that we feel the word “preferred” is a highly misleading term and should not be used in any of these cases. Why? Because it raises the whole question of what “preferred” actually means and who is doing the preferring.

I may “prefer” to have two spoons of sugar in my coffee because I like the taste better. But that doesn’t mean it is a good idea. My primary care provider might “prefer” me to have no sugar in my coffee (since I have a history of high cholesterol and a myocardial infarction). If what I put in my coffee was to be determined by him, I would stop drinking coffee! However, if he chooses to “recommend” that I have no sugar in my coffee, I understand the recommendation and I would decide to use the minimum amount of sugar  that made the taste of coffee acceptable to me.

Two large, randomized clinical trials (PIVOT and ProtecT) have shown that close monitoring of men with favorable-risk forms of localized prostate cancer is as effective — in terms of overall survival — as immediate active treatment (with surgery or radiation therapy), and comes without the risk for side effects like loss of erectile/sexual function, various forms of incontinence, and a spectrum of associated psycho-social disorders that affect the quality of life of the patient and his family members too. Were these trials “perfect”? No. They most certainly weren’t. As just one example, they both included men who were almost certainly NOT good candidates for active surveillance in the first place!

In Sweden today, some 90 percent of men with well-defined forms of low-risk prostate cancer are initially managed on active surveillance.

In the UK today, a surgeon who operates on a man with a low-risk form of prostate cancer must provide written justification for his or her decision to do so because active surveillance is considered to be the initial standard of care for all such patients.

Now we do need to be very clear about several factors that affect the appropriate application of active surveillance — here in the USA and elsewhere around the world:

  • The selection of appropriate patients for management on active surveillance should, in our opinion, be based on high-quality data and a shared decision between the patient and his doctor. Such high-quality data can be expected — at this time — to include such factors as a confirmatory MRI/TRUS-guided fusion biopsy — preferably by transperineal as opposed to transrectal methodology — and (perhaps) genomic testing of selected biopsy tissue.
  • Active surveillance is a form of proactive management that is intended to allow for curative treatment as and when necessary for the individual patient. It is NOT the same as “watchful waiting”, which is only intended to monitor a patient for his risk of pain and unnecessary suffering associated with the development of metastatic prostate cancer.
  • Active surveillance requires close  patient management through the use of a series of regular biomarker tests, imaging tests, and additional biopsies as necessary. Just monitoring a man’s PSA level every 6 months or so does NOT meet standards of good practice for active surveillance.
  • Not all men with low-risk forms of localized prostate cancer are good candidates for initial management on active surveillance. Men with certain types of hereditary genetic markers for cancer risk (e.g., BRCA1/2 mutations) or very high levels of disease-related anxiety may well be appropriate for earlier, invasive treatment (if this is a shared decision between patient and doctor).

The real problems here are twofold:

  • The unwillingness of the physician community within the NCCN to stand up and take a hard decision about the right thing to do.
  • The social problem that Americans in the mass do not understand that not all cancers are “deadly”.

It is past time to address these problems, and the NCCN can actually take a major step toward resolving both of these problems by acknowledging that low-risk, localized prostate cancer offers us an opportunity to re-write the way we think about the appropriate management of all forms of low-risk cancer and start to educate patients accordingly.

10 Responses

  1. Will NCCN reconsider its downgrade of active surveillance as patient advocates stand in solidarity and call NCCN to reverse its policy change? Where do the Prostate Cancer Foundation and the American Urological Association stand on this vital issue for men with low-risk prostate cancer? For more, see here. Let Dr. Ted Schaeffer, chairman of the NCCN prostate cancer guideline panel, know where you stand:

  2. Maybe it requires a footnote: AS is preferred unless
    • Decipher or Prolaris score is high risk, or somatic genomics show PTEN loss or TMPRSS2:ERG fusion
    • germline genomics show presence of HRR mutations
    • you are African-American
    • there is PNI
    • mpMRI-estimated tumor volume > 0.5 ml.
    If any of the above apply, further discussion of risks and options is required.

  3. Allen:

    The NCCN guidelines always come with a detailed discussion of all the ifs, ands, and buts that may be relevant under specific circumstances. What is under discussion here is ONLY the core guideline statement. The potential list of the ifs ands and buts is a good deal longer then the “footnote” you are proposing, although these are certainly relevant.

  4. Over 30k American men die each year of this disease. Approaching 500k on ADT. And still no standard screening standards. My initial diagnosis was Gleason 3+3, Genomic testing indicated low intermediate risk. Fortunately I ignored AS. Opps biopsy missed worst bits and after RP and salvage RT failed salvage extended lymph node surgery confirmed cancer in para aortic lymph nodes. So puzzling that medical industrial complex gets this disease so wrong.

  5. Actually, I am saying AS may not be preferred over RP or RT if any of those 5 conditions obtain. I think NCCN erred last year in making an unqualified statement that it is preferred for all low risk. Those are the only exceptions I know of – what other exceptions are there?

  6. Allen:

    Respectfully, no one has ever said that AS is preferred or recommended for ALL men with low-risk prostate cancer. Such guidelines are a generalized statement for “most” men, not “all” men. Each individual has to be carefully assessed to see if he meets the criteria for low- or very-low risk. This is not being properly done in the US at present. And the most obvious example of another exception that you have omitted is clinically severe anxiety. There is a distinction between men who are “anxious” about being on AS and those who are so anxious that it is or could severely impact their quality of life.

  7. Dear Mr. Wadsworth … It is not unusual for a man to initially be diagnosed with a Gleason score of 3 + 3 = 6 and then, on full work up, to clearly not meet criteria for low-risk prostate cancer. That appears to have been the situation in your case. And I suppose there is also the question of just how long ago your initial biopsy was carried out.

  8. I think it’s very important for guidelines writers to be clear on the definitions of what is low and very low risk. Allen’s 5 points are correct but I submit if any of them exists then are these patients truly “low or very low” risk and AS candidates? The point of adding these biomarkers was to find risk where PSA kinetics and basic imaging didn’t. On the other hand, African Americans and family history are classified in the early detection guidelines as high risk with screening determination in mind. There is a conundrum present when you look at early detection risk stratification for defining screening targets and localized prostate cancer risk stratifications for defining AS patients. These are not parallel definitions. That’s an area that needs improvement because it’s confusing. It’s like saying a high risk screening patient is also high risk for disease progressing and that is not a correct way to assess risk after diagnosis.

  9. Hey Tony!

    I think you are onto something. Maybe AS should have its own NCCN risk categories. For example, African-American men with, say, low volume GS 3 + 4 and < 10% pattern 4, may be at the high end of riskiness for AS. For them, the AS "treatment" may consist of quarterly PSAs, annual mpMRI, and biopsies. While, white men, with say, only 1 core of < 50% GS 6 may be at the low-risk end and require only mpMRI every 3 years.

    The NCCN risk categories came from D'Amico's analysis of RP data originally. They predict recurrence after surgery. I have previously argued that radiation should have its own risk categories (see this link and this link). Maybe NCCN is just trying to fit too many square pegs into too few round holes.

    It makes sense for physicians to do three separate risk scores for each localized PCa patient (RT, RP, and AS) which predicts his risk of recurrence if he undertakes each of those treatment options.

  10. Today, NCCN revised their low-risk guidelines to read “Active surveillance (preferred for most patients).” I’m glad they qualified it as for most low-risk patients. The new footnote goes on to explain:

    “The panel recognizes that there is heterogeneity across the low-risk group and that some factors may be associated with an increased probability of near-term grade reclassification, including high PSA density, a high number of positive cores (e.g.,>3), high genomic risk (from tissue-based molecular analysis), and/or a known BRCA2 germline mutation. In some of these cases, upfront treatment with radical prostatectomy or prostate radiation therapy may be preferred based on shared decision-making with the patient.”

    They’ve included most of the qualifications I suggested except for African-American ethnicity and PNI. Additionally, they added PSA density (at what cut-off?) and BRCA2+. I like that they are saying that even if it is not “preferred” it is nonetheless open to shared decision-making.

    I still believe that NCCN should have separate localized-risk categories for prostatectomy, radiation, and active surveillance because there are different variables that affect recurrence risk for each. But I am realistic enough to know that this is an uphill battle.

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