NCCN expands role for active surveillance in initial management of localized prostate cancer

In its most recent update to its guidelines on the management of prostate cancer, the National Comprehensive Cancer Network (NCCN) has now stated that active surveillance is a first-line option for the management of favorable, intermediate-risk prostate cancer. This new recommendation is discussed in some detail in an article posted yesterday on the Medscape web site.

Basically, this means that the NCCN is now recommending active surveillance as a first-line management option for:

  • All men with very low-risk prostate cancer and a life expectancy of 10 or more years
  • All men with low-risk disease and a life expectancy of 10 or more years

It is also stating that active surveillance can be considered as a first-line management option for

  • Men with favorable intermediate-risk prostate cancer that has predominant Gleason grade 3 pathology (i.e., Gleason score 3 + 4 = 7), a percentage of positive biopsy cores < 50 percent, and no more than one NCCN intermediate risk factor (i.e., a clinical stage of T2b or T2c or a PSA value of 10 to 20 ng/ml)

This new recommendation will be controversial for many in the urology community, but it does appear to be justified by the data published from the long-term follow-up of patients in large, active surveillance cohorts.

Patients willing to consider active surveillance as a first-line management strategy for favorable, intermediate-risk do need to appreciate that there is a significant likelihood that they will need treatment at some point in the future. In other words, active surveillance in this scenario is primarily intended to defer treatment until it becomes necessary and not to avoid treatment altogether. However, for a man in his mid to late 50s or older who can therefore maintain good erectile and sexual function and avoid risk of problems with incontinence for (say) another 5 to 10 years before curative treatment actually becomes necessary, this may be a very big deal indeed.

As noted in the Medscape article referenced above acceptance of active surveillance as a first-line management strategy here in the USA is still much lower than the acceptance level seen elsewhere in the world:

  • In Sweden in 2013, 78 percent of men with very low-risk prostate cancer and 59 percent of men with low-risk prostate cancer received active surveillance as first-line management.
  • Data from the CaPSURE database collected between 2008 and 2013 suggest that here in the USA about 38 percent of all newly diagnosed men with low-risk prostate cancer were being managed on either active surveillance or watchful waiting.
  • Estimates suggest that as many as 50 percent of newly diagnosed men with low-risk prostate cancer in the state of Michigan are being initially managed on either active surveillance, but that only 8 percent of newly diagnosed men with low-risk disease are being initially managed on active surveillance nationally in the US.

There are multiple reasons why active surveillance has a slower uptake here in the US compared to Europe. There are fundamental financial incentives for urologists and radiation oncologists to want to treat newly diagnosed patients as opposed to monitoring them. The complex healthcare system in the US makes it hard to gain adherence to specific sets of guidelines by doctors and by patients. And then there is the American societal attitude to “health”, which tends to operate from the presumption that all disease is or ought to be diagnosed early and cured immediately — whether this will actually benefit the patient in terms of increased life expectancy or improved quality of life or not.

The “New” Prostate Cancer InfoLink is pleased to see this expansion in the NCCN’s recommendations for the role of active surveillance. We believe that this will be in the interests of a very large number of men initially diagnosed with favorable, intermediate-risk prostate cancer, although it may take a while for a lot of men and their doctors to “buy in” to why this is in their best interests.

7 Responses

  1. I would be one of those men with “favorable intermediate” who would now be considered for active surveillance as a first-line management option under new NCCN guidelines: 3 + 4, T1c, PSA = 7 with a doubling time of ~36 months, 4 cores out of 12 positive for prostate cancer (< 5%, < 5%, 10% all 3 + 3, and 10% for 3 + 4). Last fall I chose to undergo SBRT treatment, after considering AS.

    My rationale: I concluded that I had only ~1-2 years based on PSA doubling time before I would have to seek some form of curative treatment and the earlier the better to maximize success. Add to this the uncertainty that the biopsy successfully determined the highest lesion (i.e., were there higher grade prostate cancer lesions that the biopsy missed?) and a concern that the 3 + 4 lesion (apex) could soon spread outside the capsule — I opted for curative treatment.

    Diagnostic capabilities are improving and will continue to improve. If in the near future diagnostic capabilities were to be improved enough to allay the above concerns, one would then have the information to make a rational judgment as to whether (and how long) to follow the AS prescription. Some day I have no doubt that we will have these diagnostic capabilities available to us. Until that happy day, I suspect that many guys in my situation would rather choose to err on the cautious side and opt for curative treatment.

  2. Dear T.:

    No one is suggesting that men like you “have to” or even “should” initiate management on active surveillance following initial diagnosis. These are all very personal decisions, and yours was and remains a perfectly reasonable one.

    However, just as you wanted to err on the side of therapeutic caution, there have long been other men with similar diagnoses who have had to fight hard with their doctors in order to avoid immediate invasive treatment because their priority was quality of life. Some (but far from all) men with a diagnosis like this have clearly been shown to have forms of prostate cancer which can be monitored for 15+ years without any sign of clinically significant disease progression.

    The new NCCN guidance gives additional validation to such decisions on the part of patients, and tells physicians that such decisions are reasonable and are supported by a significant amount of sound data.

  3. Another consideration in deferring treatment is the ongoing improvement in surgical, radiation, and other therapies as well as development of innovative techniques. Hopefully in the not too distant future focal therapy will become viable for micro-focal, higher grade prostate cancer.

  4. This IS a “very big deal indeed”!

    We need to keep in mind that active surveillance and watchful waiting can, in my mind should, include whatever lifestyle and mild medication tactics we can use to slow (or halt, or reverse) the growth of the cancer. For instance, Dr. Laurence Klotz, MD, perhaps the leading expert in AS, is very interested in the use of 5-alpha reductase inhibitor (5-ARI) drugs (finasteride/Proscar or dutasteride/Avodart) to combat the disease, and lifestyle tactics (exercise, diet, nutrition – including pomegranate extract or juice, stress reduction) seem helpful, and for some of us a statin, metformin, aspirin or all of these may work well.

    Another strategy is to have a limited course of androgen deprivation therapy (ADT, aka hormonal therapy). Supportive published studies do exist but are quite limited and far from conclusive. I’ve seen studies from two different practices using one-time ADT2 or ADT3, with and without 5-ARI as maintenance. It is clear that for some men this is all that is necessary long term. I have a friend who has done this very successfully with ADT3 and now Avodart as maintenance for more than 10 years. As I recall, he stopped ADT3 at the 13 month point. Such a course of ADT may be attractive to someone who wants the advantages of deferring an intrusive therapy but also is not yet comfortable with active surveillance.

  5. Dear Jim:

    Anyone who is treated with even a single shot of an LHRH agonist (let alone long-term 5-ARI therapy) is absolutely not on active surveillance, and, as far as I know, no one has ever done a randomized, prospective trial to compare true AS with surveillance after any form of short course of ADT. Case cohorts of the type you refer to are invariable retrospective and tell us little to nothing beyond the fact that such therapy “works” in selected patients.

  6. Of course I fully concur with your statement that ADT is not active surveillance. (Also, glad to see you back as feisty as ever!)

    I simply wanted to make the point that there is a middle course strategy worth consideration that lies between observation and intrusive treatments. My strong impression, based on tracking ADT3/IADT3 publications (formal and informal) for years (plus long personal experience and talking to survivors also on ADT3/IADT3) is that it has a marked favorable impact on almost all men who try this unless their disease is well advanced. (It works on some of those well-advanced cases too, as it did for mine.) A key advantage of one-time ADT for about a year is that for the vast majority of us side effects are reversible, with recovery back to the pre-treatment baseline, usually including substantial recovery by the 3-month point and virtually full recovery by the 6-month point. Thirteen to 17 months seems to be the sweet spot for treatment duration, plus continuing maintenance with one of the 5-ARI drugs that are very well tolerated by a large majority of men, but with some shorter courses (down to 9 months) possibly effective, but based on scant study.

    I am not impressed with single drug ADT as short-course primary ADT, and I’m a lot more impressed with ADT3 than ADT2, but, as you indicate, there are not many studies of primary ADT. I too know of no randomized studies of AS versus a short (at least 9 months) course of ADT. Of course more published research would help, but I’m not holding my breath, especially in our current truly wonderful environment where much more effective drugs for ADT (especially Xtandi/enzalutamide, Firmagon/degarelix and Zytiga/abiraterone), as they move toward approval/use for patients with less advanced disease) are legitimately the primary targets of researchers rather than the less effective older generation drugs. Regarding randomized trials, another obstacle is that the doctors who are enthusiastic about intermittent triple blockade have seen such striking success in their own practices that I doubt they could ethically serve as primary investigators where patients would be randomized to even IADT2, let alone IADT1. (That said, there is a role for each kind of ADT and IADT for certain patients, including ADT that includes only an antiandrogen or an antiandrogen plus a 5-ARI drug.)

  7. Jim:

    You are missing my and Allen’s point entirely. Where are the data to even suggest that someone should start ADT at all unless there is clear risk for metastasis (which was certainly evident for you and a number of other men who seem to have benefited from IADT2 and IADT3)? I don’t care whether it is a single dose of an LHRH agonist or 3 months of an antiandrogen alone or the initiation of some form of IADT.

    There were data from the use of high-dose antiandrogen monotherapy (with bicalutamide 150 mg) in high-risk, non-metastatic patients some years ago in Europe, but the FDA rejected that indication for bicalutamide because the risk for side effects was too high in their opinion (although this indication was approved in Europe). However, again, this was only for high-risk patients.

    In the context of non-high-risk patients, our point is that there appears to be no justification for initiation of ADT of any type at all. All that one is doing under such circumstances is managing the patients’ PSA levels, not treating disease. For patients with high risk for metastasis or evident metastasis, we are discussing a whole different ball game. In that game, your comments about ADT are relevant (albeit not well proven), but we aren’t talking about those patients.

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