Intraductal carcinoma of the prostate: of risk, outcomes, and Gleason scores

In a recent article in the American Journal of Surgical Pathology, Khani and Epstein have argued that patients initially diagnosed with intraductal carcinoma of the prostate (IDC-P) should have this reported as a separate class of prostate cancer, with no reference to the patients’ Gleason scores.

Now this is a relatively controversial recommendation — even for Johns Hopkins — and so we need to try and understand why someone of Dr. Epstein’s stature would make a recommendation like this.

It is well appreciated that IDC-P is commonly found in biopsy specimens from patients who also have clear indications of invasive prostate carcinoma along with Gleason pattern 4 or 5. Such patients also, commonly, and not unsurprisingly, go on to have unfavorable outcomes to treatment. However, there is much less data available from patients initially diagnosed with IDC-P and concomitant invasive cancers of low grade (i.e., Gleason pattern 3).

Khani and Epstein carried out a retrospective analysis of the clinical outcomes and the post-surgical pathological findings of patients in the Johns Hopkins pathologic consultancy files from 2001 to 2014.  All patients were required to have

  • A Gleason score of 3 + 3 = 6 on biopsy or at TURP
  • No invasive, higher Gleason grade tissue on biopsy
  • A finding of IDC-P on biopsy or TURP

Here are their core study findings:

  • 73 such patients were identified in the Johns Hopkins pathological consultancy files.
  • 62/73 patients also had clinical follow-up information available.
  • Known treatments among the 62 patients for whom follow-up information was available were
    • Active surveillance in 11 patients (of whom 6 went on have treatment for progressive disease)
    • Radical prostatectomy in 14 patients
    • External beam radiation therapy in 31 patients
    • Immediate androgen deprivation therapy (ADT) in 1 patient
    • Cryotherapy in 1 patient
    • Immediate chemotherapy in 4 patients, all of whom had metastatic disease at diagnosis
  • With respect to post-treatment pathology for the 14 men treated by radical prostatectomy,
    • 12/14 (86 percent) had extensive IDC-P.
    • 3/14 (21 percent) had Gleason scores of 3 +3 = 6.
    • 5/14 (36 percent) had Gleason scores of 3 + 4 = 7.
    • 4/14 (29 percent) had Gleason scores of 4 + 3 = 7.
    • 2/14 (14 percent) had Gleason scores of 4 + 4 = 8.
  • With respect to the pathologic stages of the 14 men treated by radical prostatectomy
    • 5/14 (36 percent) had a pathologic stage of pT2.
    • 5/14 (36 percent) had a pathologic stage of pT3a.
    • 4/14 (28 percent) had a pathologic stage of pT3b.
  • At 3 years of follow-up, there was an actuarial rate of disease progression of 20 percent among the 45 men who were initially treated with either radical prostatectomy or external beam radiation therapy.

Now the first thing to note is that we are talking small numbers of patients. The second is that, among the 14 men who went on to have an immediate  radical prostatectomy, 11 (79 percent) were under-staged at biopsy, which is a very high percentage. The third is that there are a variuety of opinions within the surgical pathology community about whether Gleason scores should be considered in the evaluation of patients diagnosed with IDC-P.

Based on this study, Khani and Epstein conclude that

… most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.

But there may be an alternative way to look at these data, which is to recommend that all men diagnosed with IDC-P and Gleason 6 disease on biopsy should be given a multiparametric MRI and a repeat MRI/TRUS fusion biopsy prior to any decisions about their management. It is clear that a significant percentage of patients with Gleason 6 disease and any amount of IDC-P are at high risk for relatively aggressive disease, but there is a subset of patients who may be manageable on active surveillance for a period of time. By being able to confirm which men really do appear to have IDC-P and a Gleason score of 6, it may be possible to give such patients the option of deferred therapy, at least for some period of time, before treatment is really necessary.

4 Responses

  1. One has to question the Gleason scores of the men with IDC-P and Mx disease as 3 + 3.

  2. Dear Rick:

    That was exactly the point of the final paragraph of the commentary. Is it not possible for us to tell (most of the time) which of these patients really have Gleason 3 + 3 = 6 disease before we have to take their prostates out?

  3. Agreed Mike … but I am focused particularly on data credibility and the four who had 3 + 3 at the same time as bone Mx and immediate chemotherapy; it should have given Epstein cause for thought — especially 4 out of 73 or 5.5%.

    Now one could argue that IDC-P causes an exception, but for me it questions the credibility of the data.

  4. Rick:

    This was just one of the reasons why I questioned the proposed hypothesis. The biopsies done on these men were almost certainly done on,ly to confirm a diagnosis of prostate cancer and the chances that they were Gleason 6, even at diagnosis, would seem to be near to zero.

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