Active surveillance in men with Gleason 3 + 4 = 7 prostate cancer at diagnosis


A critical question for men with favorable intermediate-risk prostate cancer (based primarily on a Gleason score of 3 + 4 = 7) can often be, “How safe would it be for me to go on active surveillance for a while after initial diagnosis?”

So let us be very clear about one thing immediately.

A man with favorable intermediate-risk prostate cancer (e.g., a clinical stage of T1c or T2a; a PSA level of 5.0 ng/ml; and a Gleason score of 3 + 4 = 7, with 15 percent of one positive biopsy core out of 12 showing cancer) who starts on active surveillance is always going to have a higher probability of the need for later treatment if he starts on active surveillance that an otherwise identical man who has only Gleason 3 + 3 = 6 disease.

So the question about “How safe” it would be for such a man to start on active surveillance as opposed to having immediate treatment is really about how effective treatment will be later when it actually becomes necessary.

The abstract of a presentation by Kalapara et al., to be given at the upcoming annual meeting of the American Urological Association, provides us with some reassuring information that addresses this precise question.

Kalapara et al. used information from a prospective database of men on active surveillance at Monash University in Australia to look at what was found among all men in that database (enrolled between 2000 and 2017) who underwent a delayed radical prostatectomy after being initially managed on active surveillance. All the men in their active surveillance database had to have a clinical stage of ≤ T2, a PSA level of < 20 ng/ml, a Gleason score of ≤ 3 + 4 = 7,  and fewer than half of their biopsy cores showing positive indications for prostate cancer at the time of diagnosis. All the men in the database were also given a confirmatory biopsy at 1 year and surveillance biopsies at least every 3 years thereafter.

The patients who started on active surveillance and then went on to have a radical prostatectomy were divided into two groups:

  • Men who started active surveillance with a Gleason score of 3 + 3 = 6 and had surgical treatment while their Gleason score was still 3 + 3 = 6 or immediately after upgrading to a Gleason score  of ≥ 7 (Group A)
  • Men who started active surveillance with a Gleason score of 3 + 4 = 7 and those who started active surveillance with a Gleason score of 3 + 3 = 6 disease, then progressed to a Gleason score of 3 + 4 = 7 but remained on active surveillance prior to their surgery.

After patients had surgery, they were assessed as to whether their post-surgical pathology and clinical outcomes were either favorable or unfavorable. Unfavorable disease was defined as prostate cancer with a Gleason score of ≥ 4 + 3 = 7 or pathological stage T3 and biochemical failure (i.e., a post-surgical PSA level > 0.2 ng/ml).

Here is a summary of the study findings:

  • 359 men were initially enrolled on active surveillance and followed for an average (mean) of 72.9 months
    • 286 of these men started with a Gleason score of 3 + 3 = 6.
    • 73 men started with a Gleason score of 3 + 4 = 7
  • 147/359 men (40.9 percent) went on to have some form of treatment.
  • 117 of the men who went on  to have treatment elected to have a radical prostatectomy
    • 77/117 men were in Group A
    • 40/117 men were in Group B
  • There were no statistically significant differences between the men in Group A and Group B (on average) with regard to their ages, their PSA levels at diagnosis, or their times from enrollment to progression.
  • Pathological results after surgery were similar between the two groups.
    • In Group A
      • 42/77 patients (54.5 percent) had unfavorable prostate cancer.
      • 23/77 patients (29.9 percent) had a Gleason score of ≥ 4 + 3 = 7.
      • 30/77 patients (39.0 percent) had pT3 disease.
    • In Group B
      • 21/40 patients (52.5 percent) had unfavorable prostate cancer.
      • 9/40 patients (22.5 percent) had a Gleason score of ≥ 4 + 3 = 7.
      • 16/40 patients (40 percent) had pT3 disease.
  • Rates of biochemical recurrence after surgery were also similar.
    • 12/77 men in Group A (15.6 percent) had biochemical recurrence and salvage therapy was successful in 10 of these patients.
    • 6/40 men in Group B (15.0 percent) had biochemical recurrence and salvage therapy was successful in all six of these patients.
  • 2/77 men in Group A (2.6 percent) progressed to have metastatic disease.
  • No patients had died of prostate cancer.

Kalapara et al. conclude that

Patients with GS 3 + 4 = 7 prostate cancer are more likely to progress to treatment on AS than those diagnosed with GS 6 disease. However, rates of unfavorable disease and BCR are equivalent between men with GS 6 and GS 3 + 4 = 7 disease who undergo delayed RP after AS. As such, our results support the safety of including selected men with GS 3 + 4 = 7 disease in AS programs.

The “New” Prostate Cancer InfoLink would point out that this cohort of “real world” patients who started on active surveillance was actually a higher-risk group of patients that those enrolled by Klotz et al. in the original Sunnybrook trial of active surveillance in that men with PSA levels as high as 19.9 ng/ml were eligible for enrollment, as were men with clinical stages T2b and T2c, and this cohort includes a higher proportion of men with Gleason 3 + 4 = 7 disease as well.

Despite the wide spectrum of patients who seem to have been eligible for inclusion in this study, the men with initial Gleason scores of 3 + 4 = 7 who went on to have surgery seem to have done just as well as the men with initial Gleason scores of 3 + 3 = 6, and this should offer a greater degree of confidence that active surveillance is a perfectly reasonable initial management strategy for men with favorable intermediate-risk prostate cancer. However, …

Even your sitemaster — who freely admits to having been a long-term advocate for active surveillance — is not sure he would consider active surveillance if he was diagnosed tomorrow with a clinical stage of T2b and a PSA level of (say) 17.0 ng/ml and a Gleason score of 3 + 4 in less than 50 percent of two positive biopsy cores out of 12 (although such patients do appear to have been eligible for inclusion in this study).

7 Responses

  1. I know they know this, so probably they will publish it, but they need to filter for sub-patterns of GP4, particularly cribriform. Even without that, thank you for the direct hit in my wheelhouse, Kalapara et al and @SM!

  2. It is interesting that the 2 mets were in the GP3 group, and I note the talk of 12-core biopsies. Suggestive of the point that it is generally better to know you have GP4 than to think you have not.

    Is there a repetition of “3 + 4” above, for “3+3”?

  3. Re “Is there a repetition of “3 + 4” above, for “3 + 3”?

    No. I don’t think so.

  4. But I KNOW so :- )

    “Despite the wide spectrum of patients who seem to have been eligible for inclusion in this study, the men with initial Gleason scores of 3 + 4 = 7 who went on to have surgery seem to have done just as well as the men with initial Gleason scores of 3 + 4 = 7”

  5. And you are right and it has been corrected.

  6. I want to share my experience in regards to active surveillance with a Gleason score (GS) of 3 + 4.

    I had GS 3 + 4 with a PSA baseline of 4.8 and then a month later it dropped to 4.2. The DRE exam showed some hardness. I was being treated for BPH by my PCP and dealing with that for about 5 years.

    In June 2017 I elected to have radical prostatectomy & pathology report, all the cancer was inside the prostate capsule. It was noted pathology examined the other tissues which were also removed. I had been referred to a local urologist/surgeon who exceeded my expectations of his intense experience and knowledge and had 2 years of robotic assistance training at Tulane. As an example of his experience, I asked how many prostatectomies he had done in the past month. His response was, “Around 22 completed”. I also asked him about me waiting since I had intermediate risk disease. I was 69 when my yearly PSA showed risk for cancer. I had four positive core samples out of 12 (three were 3 + 3 and one was 3 + 4). He said he would advise me not to do “watch and wait” because 3 + 4 was still a concern. I wanted to do more research and he felt I had about 6 months before more issues came about. I finally chose to have the da Vinci nerve-sparing RP procedure and the pathology report showed the cancer beginning in the neck of the urethra inside the prostate. I am glad I took his advise and have had three recent PSAs which were all 0.01. The expertise of the surgeon makes a difference … in my opinion. I felt this surgeon talked to me like a family member. He also said “as a patient I was in very good health for someone of 70 years old, which made a big difference. I discovered that many men who I had talked to even a couple of years younger could not have a radical prostatectomy because of their general health. I did also hear from these guys, “Oh I did not want to deal with the side effects of surgery”. Some admitted about the sexual erectile dysfunctions, then changed the subject.

  7. Dear William:

    There are no “rights” or “wrongs” here. Other men like you might have very reasonably made any one of several other possible decisions — inclusive of staying on active surveillance for longer and then having treatment some time later when there were initial signs of disease progression. These are very personal and individualized decisions.

    Having said that, there is no doubt at all that the skill and the experience of the physician is always important when it comes to having any type of treatment … and the “skill” part is a very important part. Not all surgeons who have done lots of radical prostatectomies are necessarily good at this operation.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s

%d bloggers like this: