A new article from the group at Johns Hopkins has now confirmed that rates of prostate cancer-specific mortality and progression to metastatic disease are extremely low at 15 years of follow-up in their 18-year-long active surveillance cohort.
The new paper by Tosoian et al., just published in the Journal of Clinical Oncology (and supported by data in a media release from Johns Hopkins that are reported on the ScienceDaily web site) makes an number of key points that correlate extremely closely with the data previously published by Klotz and his colleagues in Canada — especially when one bears in mind that the Johns Hopkins protocol has almost certainly been the most restrictive current protocol accepting patients for inclusion on active surveillance.
Here are the core data reported by Tosoian and his colleagues:
- Their cohort included 1,298 men with an average (median) age of 66 years.
- Average (median) patient follow-up of 5 years (range, 0.01 to 18.00 years).
- Survival rates are
- 93 percent and 69 percent overall survival at 10 and 15 years respectively
- 99.9 percent prostate cancer-specific survival at both 10 and 15 years
- 99.4 percent metastasis-free survival at both 10 and 15 years
- The cumulative incidence of grade reclassification was
- 26 percent at 10 years
- 31 percent at 15 years
- The cumulative incidence of curative intervention was
- 50 percent at 10 years
- 57 percent at 15 years
- Average (median) treatment-free survival was 8.5 years (range, 0.01 to 18 years).
- Factors associated with grade reclassification were
- Older age at diagnosis (hazard ratio [HR] = 1.03 for each additional year)
- PSA density at diagnosis (HR = 1.21 per 0.1 unit increase in PSA density)
- Higher number of positive biopsy cores at diagnosis (HR = 1.47 for each additional positive core)
- Factors associated with curative intervention were
- PSA density at diagnosis (HR = 1.38 per 0.1 unit increase in PSA denisty)
- Higher number of positive biopsy cores at diagnosis (HR = 1.35 for one additional positive core)
Tosoian et al. concluded bluntly that:
Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.
In addition, the report on the Science Daily web site makes the following important points:
- Over 10 and 15 years, the cumulative risk of a grade reclassification to a level that would be considered potentially lethal in most cases but still curable was no more than 5.9 percent for both very low-risk and low-risk prostate cancers.
- 109/1,298 men (8.4 percent) opted for surgical or radiation treatment despite the absence of significant change in their prostate cancer status under the stringent Johns Hopkins protocol.
- 47/1,298 men (3.6 percent) actually died of non-prostate cancer causes, mostly from cardiovascular disease and 9/47 had received treatment for their prostate cancer.
- 2/1,298 men (0.15 percent) actually died from prostate cancer.
- One of these men died after 16 years in the active surveillance program.
- The other man died 15 months after his diagnosis and a recommendation of active surveillance at Johns Hopkins, but was actually monitored at another hospital.
- 3/1,298 men (0.23 percent) in the program progressed to have metastatic prostate cancer.
- Tosoian et al. calculate that men in the program were 24 times more likely to die from a cause other than prostate cancer over a 15-year span.
There can now be no serious doubt about the potential value of active surveillance as a management strategy for patients with very low-, low-, and (potentially) “favorable” intermediate-risk disease. The questions that need resolution today are what best practices should be with respect to such matters as:
- Entry criteria onto active surveillance protocols (specifically including PSA density data)
- The necessity for repeat biopsies within 12 months of diagnosis as a condition for inclusion on active surveillance protocols
- The frequencies and criteria for subsequent repeat biopsies (based, for example) on modern MRI data
Data like those now published by Klotz and his colleagues in Canada (based on a significantly less stringent protocol) and by Tosoian et al. should give men with favorable risk prostate cancers a great deal more confidence about the safety of being managed on active surveillance over time, and should also help to reduce the number of men who feel the need to have early treatment while on active surveillance if there is no signal that treatment would be advisable.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk | Tagged: active, Johns Hopkins, outcomes, protocol, surveillance |
THE "NEW" PROSTATE CANCER INFOLINK 
We see from the above how important it is to have a correct diagnosis and correct communication between pathologist, urologist, and patient. I am trying to gather information on this process. I invite all prostate cancer patients to respond to this link. Thanks for your help.
wOOt! :-)
Very encouraging! As you correctly point out, Johns Hopkins has the most restrictive protocol. There may be many men who would be good candidates under the Klotz protocol, but were rejected by this one. Also many men had curative intervention earlier due to the enhanced restrictions. Some “back of the envelope” calculations: At 15 years, 57% had curative intervention, but only 31% had grade reclassification. So 26% had curative intervention without grade reclassification. But only 8% “opted for surgical or radiation treatment despite the absence of significant change in their prostate cancer status under the stringent Johns Hopkins protocol.” I suppose that leaves 18% who had interventions only because of increasing number of positive cores or PSA density. It would be great to have a clinical trial where men were randomized to one protocol or the other (just pipe-dreaming!).
Thanks for posting this highly important study! I will mention this article at our Us TOO planning group this evening. This study further establishes active surveillance (AS) is a sound approach, arguably the prime, wise choice for men with low and especially very low-risk prostate cancer. I have a few thoughts and questions.
What a long way we have come from the first article published on results back in 2002 (Klotz), back when even he still referred to it as “expectant management” or even “watchful waiting”! I am aware of seven major centers with AS research programs and am curious whether there are others. The seven are: the University of Toronto, Sunnybrook (Klotz), Erasmus Medical Center (Netherlands, Schröder), Johns Hopkins (Carter), UCSF (Carroll), Memorial Sloan-Kettering (Carroll), M. D. Anderson (Babaian), and Royal Marsden. Are there other leading centers, especially with long-running series?
For years certain leading urologists have opposed AS, fearing that the “escape of just one cancer cell” would doom many of the participants. Clearly that has been disproven. One of those doctors was Dr. William Catalona, MD, recently at Northwestern. Has he changed his mind about AS?
I’m curious whether the rates of reclassification of Gleason grades include cases where the grades are reduced. The low cumulative incidence of reclassification to potentially lethal levels suggests that may be the case: “Over 10 and 15 years, the cumulative risk of a grade reclassification to a level that would be considered potentially lethal in most cases but still curable was no more than 5.9 percent for both very low-risk and low-risk prostate cancers.”
Finally, with persuasive evidence of the effectiveness and safety of AS piling up, coupled with evidence of rapidly increasing use of AS, is there any sign that the US Preventive Services Task Force has noticed and will factor in this “cure for over treatment” in a revised recommendation that favors smart screening for prostate cancer.
Dear Jim:
Since you had to have a Gleason score of 6 to be eligible for enrollment in the Johns Hopkins AS protocol, and a Gleason score of 6 is the lowest Gleason score now recognized by Johns Hopkins, I can see no way that anyone’s grade could have been “down-graded” in this study.
With respect to whether Dr. Catalona has changed his views about active surveillance … does it really matter? The data speak for themselves.
The 0.23% of men who progressed to Mx with a 3 + 3 original diagnosis is consistent with the Mayo observations, albeit 31% were upgraded by 15 years.
I am not familiar with the John’s Hopkins AS protocol but assume it is restricted to 3 + 3.
Ok. I just got my results. 1 out of 18 was positive and that one was 10%. Gleason 3 + 3. What do I do? keep an eye on it, radiation, or surgery. I’m 62 years old and healthy except for this. No history of cancer in my family. Thank you in advance.
Dear Ernesto:
If you join our social network, it was specifically designed to help individual patients (and particularly the newly diagnosed patients like you) understand all their options and ask appropriate questions of their doctors.
Hi Ernesto,
Additional information that would help the social network help you includes your current PSA level, past PSA results to help show velocity as well as a trend or pattern, whether your cancer was assigned a “stage” (very likely), any Digital Rectal Exam (DRE) result (also very likely in your file), any PSA Density estimate by your doctor (PSA divided by the size of the prostate), your age, any serious other health conditions, and any symptoms that rarely these days indicate possible prostate cancer.
Based on what you have provided so far, I’m envious of your situation!
Re Dr. Catalona’s current view of active surveillance (AS):
Hi Sitemaster again. I’m responding to your reply to me of September 1, 2015 at 5:22 pm. My first reaction was “of course, his view really no longer matters” to the adoption of active surveillance overall. But I’m back to my first viewpoint: if a staunch opponent of AS like Dr. Catalona has changed his view, that would suggest opposition to AS has crumbled. I just checked the web, and there is evidence he is now moving toward acceptance of active surveillance.
Here’s a URL for a statement in the spring of 2015 by him on research to support better identification of men suitable for AS based on genetics: http://drcatalona.com/quest/spring-2015/article5.html . This statement appears to be substantially more receptive of AS than a statement he made in the summer of 2014 at http://www.drcatalona.com/quest/summer-fall-2014/article1.html . The 2014 statement comments on the superiority of surgery to watchful waiting, as indicated in a well known Scandinavian study, but does not draw the needed sharp distinction between watchful waiting and AS. It emphasizes what Dr. Catalona evidently views as significant risks of AS. On the other hand, he emphasizes risks for intermediate-risk men on AS using evidence of overall survival, which I take as a faulty approach for his purpose; this is also in the spring of 2015, so he isn’t departing the field quietly.
Dear Jim:
I and many others (with much more wisdom that I) have long believed that Dr. Catalona has — for years — massively over-emphasized the value of PSA testing in the diagnosis of prostate cancer and, to an even greater extent, over-emphasized the benefits of radical surgery in the treatment of favorable-risk prostate cancer while under-emphasizing the risks.
The fact that he may now, grudgingly, be willing to acknowledge the value of active surveillance in men with very low-risk disease is not, to my mind, of relevance any longer. It is the behavior of a man who has long put more emphasis on his personal point of view than in the evidence clearly apparent to those with more open minds to the actual data.
Amen to your comment!