New grade group system predicts risk for prostate cancer-specific mortality

According to a report on the Renal & Urology News web site this morning, a new paper about to be published on line in European Urology (by He et al.) has shown that the new ISUP staging system can be used to project risk for prostate cancer-specific mortality, “regardless of treatment received or clinical stage at diagnosis”.

For those who may have forgotten, the new ISUP staging system has compacted the Gleason scores down to a total of five new “grade groups” that are roughly equivalent to the older Gleason scores as follows:

  • New grade group 1 ~ Gleason 3 + 3 = 6 or lower
  • New grade group 2 ~ Gleason 3 + 4 = 7
  • New grade group 3 ~ Gleason 4 + 3 = 7
  • New grade group 4 ~Gleason 4 + 4 = 8
  • New grade grade 5 ~ Gleason 4 + 5 = 9, 5 + 4 = 9, and 5 + 5 = 10

What He at al. have shown is that, among >330,000 prostate cancer patients for whom data is available in the Surveillance, Epidemiology and End Results (SEER) database and all of whom were diagnosed between January 2006 and December 2012:

  • The cumulative incidence of 7-year prostate cancer-specific mortality is
    • 0.43 percent for men in new grade group 1
    • 0.48 percent for men in new grade group 2
    • 0.80 percent for men with new grade group 3
    • 2.13 percent for men with new grade group 4
    • 4.57 percent for men with new grade group 5
  • The risk for prostate cancer-specific mortality among men in this data set who underwent a radical prostatectomy, relative to the risk for men with new grade group 1 was
    • 1.13 times higher for the men with new grade group 2
    • 1.87 times higher for the men with new grade group 3
    • 5.03 time higher for the men with new grade group 4
    • 10.92 times higher for the men with new grade group 5

Basically, as one’s grade group goes up, one’s risk of dying from one’s prostate cancer roughly doubles with each step up from grade group 2 to grade group 5.

Now the actual paper by He et al. doesn’t yet seem to be available on line (even as an abstract), so we have no original source document to check these data against — yet.

What is of interest, however, is that the data from He et al. appear to correlate with earlier data from another paper (from a team at at Johns Hopkins, led by Misop Han), which showed that, among a cohort of just over 700 men, all diagnosed with Gleason 8, 9, and 10 prostate cancer, men with Gleason 9 and 10 prostate cancer were about twice as likely to die of prostate cancer within 4 years as the men with Gleason 8 prostate cancer.

Many older and more experienced patients are still very dubious about the value of the new grade group system as compared to the older Gleason system. The “New” Prostate Cancer InfoLink believes this is simply a matter of adaptation, and agrees with many in the pathology community that over time this new grade group staging system will be much easier for new patients to interpret that the older Gleason scores. Also, because the new grade group system inherently lumps all Gleason scores of 6 or less into new grade group 1, it will help to do away with the common misunderstanding that a Gleason score of 6 has to indicate a pretty risky form of prostate cancer (which is, of course, not the case at all).

17 Responses

  1. One small correction:

    New grade group 4 ~ Gleason 4 + 4 = 9 (should be 8)

  2. I wonder how this new information incorporates earlier tables which incorporate other factors in predicting survival rates?

  3. Dear John:

    If you are referring to things like the Partin tables and the Kattan predictive nomograms, it is my understanding that these will all be revised to take account of the new pathgological grading system as fast as reasonably possible. For while, the pathological data are going to be reported using both the Gleason grades and the new grade groups.

  4. Thanks Jake … typo now fixed above …

  5. John-
    As you can see in this Partin nomogram, it is already incorporated and has always been there. What is new here (aside from some minor changes in the ISUP grading) is a simple nomenclature change: GS 3 + 3 is called “grade group 1”, GS 3 + 4 is called “grade group 2” etc. It is a benefit to patients only by showing them lower numbers which are less scary. It does not affect clinical assessment of risk. In fact, if you believe as I do that Gleason pattern 5 should always be reported, it masks that in a small number of cases (GS 3 + 5, GS 5 + 3 and GS 4 + 4 are all grouped together in grade group 4). With the new AJCC staging system due out by year-end, there should be a new risk stratification system — that will be the more important change for clinicians.

  6. Given the emerging view strongly put forward by Klotz and by Ahmed et al. that ISUP 1 has no metastatic potential and given that their attempts to get it (Gleason pattern 3, essentially) downgraded from “cancer” status are doomed to fail (in my view), and probably rightly so given continued local invasive potential of Gleason pattern 3, is it too late to count mathematician style, from “0” (i.e., old Gleason 6 would be ISUP 0)? Thus:

    Before: Dr: “You have Gleason 6 (out of 10) cancer of the prostate”
    Patient: “I’m gonna die!”

    Now: Dr: “You have grade one cancer.”
    Patient: “Cut it out!”

    After: Dr: “You have grade zero cancer”
    Patient: “??????”
    Dr: “It means it is still cancer but has no metastatic potential and is quite likely completely safe to live with.”
    Patient: “Phew!”

  7. Dear William:

    So first, yes, I think it is too late to introduce the idea of an ISUP stage group of 0. However, there is a solution to your problem that is pretty simple.

    Now: Dr: “You have grade one cancer. It means that yes it is still cancer, but has no metastatic potential and is quite likely completely safe to live with.”
    Patient: “Phew!”

  8. I want to live on the planet you guys live on. On my planet, the conversation goes:

    Dr: You have grade group one prostate cancer. You’re in luck — someone just cancelled, so I have an opening in 2 weeks for daVinci robotic surgery.
    Patient: That’s kind of soon. If you want to treat me that quickly, I must have a serious case. My mother-in-law died of pancreatic cancer within 2 weeks of her diagnosis.
    Dr: Well, you have the lowest grade of cancer, but it is cancer, and with time it can progress to higher grades, spread, and metastasize. Also, about a third of the time we later find out that the biopsy missed the higher grade cancer that was lurking there. You were lucky to catch it early — what’s the point of putting it off? My next opening after that is in 2 months.
    Patient: Is it OK to wait that long?
    Dr: Probably. But once it grows outside of the prostate capsule, I can’t cure it for you.

  9. Allen:

    Didn’t you hear? Most of us have moved next door to Laurie Klotz in Canada. There are several reasons for this, not all related to prostate cancer! We have a spare bed in a corner in the attic, and it isn’t snowing hard this week.


  10. Very tempting! I’d better decide before Canada builds a wall to keep Americans out.

  11. WOW! A study with 330,000 patients showing mortality rates for 7 years under 0.1% for those of us with any Gleason 3s is truly revolutionary! Hopefully this stops the gross over-treatment, especially with the supposed nerve sparing daVinci robot. Worst case in the next 5-7 years, we watch/hope for medical advances to find and treat high grade, lethal prostate cancer.

    Thinking that physicians like Klotz, Horan, Schlotz, Vorstman, Busch, Epstein, Emberton, and others are smiling because they have taken a lot of heat for saying:

    (1) G3s do not kill us.
    (2) G3s rarely ever metastasize into 4s (less than 0.1%).
    (3) G3s do not have the same cancerous characteristics as G4s and should not be given the insidious “cancer” label.
    (4) G3s do not cause problems outside of the prostrate

    That said, these physicians do currently recommend that we actively monitor our “disease” for hidden or newly forming, high-grade prostate cancer (G4 or higher), and have mpMRIs that are are read by experienced pathologists knowing that second opinions are wise, easy, and relatively cheap.

    Best, ScottD

  12. It is obvious after reading the referenced article that all of the 7-year mortality data quoted are for patients after prostatectomy, just like the risk data in the following paragraph.

    May I assume that the number of patients selecting surgery is unknown?

    Thank You

  13. Maybe I missed something, but as I read the original article I was asking myself, “Are they basing their projections only on those who had RP?” Doesn’t the article say that the 7-year PCSM was after RP based on the various grade groups?

    “Using the Surveillance, Epidemiology and End Results (SEER) database, Dr Lu-Yao’s team identified 331,320 PCa patients who had primary and secondary Gleason patterns diagnosed during January 2006 to December 2012. The cumulative incidence of 7-year PCSM after RP was 0.43%, 0.48%, 0.80%, 2.13%, and 4.57% for Grade Group 1 to 5, respectively. Among men who underwent radical prostatectomy (RP), those in Grade Group 2 through Grade Group 5 had a 1.13, 1.87, 5.03, and 10.92 times increased risk of PCSM, respectively, compared those in Grade Group 1.

    The primary strength of the study was the large population-based sample size with racially diverse populations that reflect real world experiences, Dr Lu-Yao and colleagues stated. Major limitations include short follow up and the lack of PSA data at diagnosis. In addition, the investigators were not able to determine whether patients received active surveillance, watching waiting, androgen-deprivation therapy, or adjuvant therapy.”

  14. Dear Wolfram:

    You’d have to read the full text of the paper to learn the answer to that question. The abstract is now available on line, but it doesn’t address you question. What it does tell us is that the data are based exclusively on the men who had surgery (because otherwise one wouldn’t really know whether they were true Gleason 6s or whatever).

  15. Dear John: See the response I just left to Wolfram’s similar question.

  16. For me as a G2-er, the interesting thing is the low relative risk compared to G1. Apologise for OT but the view I am staking my life on is that the premium is accounted for by cribriform glands, as is possibly emerging in research (it already being clear that “the boundary” falls within Gleason pattern 4).

  17. My apologies, I totally missed the after RP for the mortality tables/rates. I would edit or remove most of my first paragraph.

    Best, ScottD

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