In my February 16th blog, I discussed a recent NIH consensus conference that concluded that "active surveillance" was appropriate therapy for men with low-grade and low-stage prostate cancer. I also discussed the conference suggestion that these low-grade and low-stage lesions should be called something other than cancer (or carcinoma). Many clinicians view both the conclusion and the suggestion as long overdue. Not everyone agrees of course, but a personal incident last week emphasized to me how much we need to consider what our words mean, both to patients and clinicians.
A colleague of mine, who I consider to be an expert in prostatic gland pathology had signed out two of 12 prostate cores as showing "atypical small acinar proliferation (ASAP)." He had based the distinction from adenocarcinoma on the presence of scattered basal cells around a few of the glands. The case had been sent to another expert in consultation at the patient's request, and he interpreted both cores as showing minimal ( <5% ) prostatic adenocarcinoma, Gleason score 3+3=6. I was asked to review the case and, not surprisingly, I found it to be a totally borderline call.
I would suggest that the following inter-related facts about this and similar cases are true:
1. Seeking additional expert consultation for a diagnosis of either minimal low-grade adenocarcinoma OR ASAP (or equivalent terms) is not only a waste of time and money, it is likely to cause nothing but increased confusion and anxiety.
2. The biologic significance of ASAP and minimal adenocarcinoma is (virtually) identical and the treatment (or more appropriately lack there of) should be identical as well.
3. Basing a clinical decision on the distinction between ASAP and minimal adenocarcinoma shows a fundamental and alarming lack of understanding of the biology of this disease.
4. If a patient or clinician is naive enough to think that this distinction should form the basis for a therapeutic decision, ie. therapy for minimal carcinoma and surveillance for ASAP (in spite of the new guidelines), then when faced with conflicting opinions, it makes no sense whatsoever to go with the more aggressive course, given the considerable morbidity associated with both radiation and prostatectomy and the indolent nature of low-grade / low-stage prostatic carcinoma.
5. There is no reproducible "gold standard" for the distinction between ASAP and minimial carcinoma and if such a standard existed, it would have no clinical meaning. Because of the limited biologic behavior of such lesions, we are unlikely to ever devise a meaningful way to discriminate between them.
6. The NIH consensus committee's suggestion that we find another name for these minimal lesions that does not involve the "C-words" (cancer, carcinoma) is, on balance, a step in the right direction. Perhaps we should simple expand rather than shrink, the use of the ASAP (or similar) designation.
7. Although, the diagnosis of clinically significant prostatic carcinoma is rarely difficult, careers have been made based on clinically insignificant diagnostic ascertions about lesions at the low end of this disease spectrum.
8. There have been many important advancements in our understanding of the variants of prostatic adenocarcinoma, refinements of our grading system, identification of carcinoma mimics, and recognition of pathologic features carrying prognostic weight. However, the trend toward diagnosing low-grade, low-stage carcinoma on smaller and smaller foci has led to widespread patient anxiety and over treatment.
9. As I hope is obvious, the above is a reflection of a much larger general problem in medicine, namely misinformed clinicians (and patients) making radically different treatment decisions based on pathologists "drawing lines" where in fact none exist and using differing terminologies that imply significant biologic differences where none exist. A short list of other similar problem areas would include:
ADH v. low-grade DCIS of the breast
low-grade dysplasia v. indefinite for dysplasia in Barrett's esophagus
severe dysplasia v. intramucosal adenocarcinoma in any GI biopsy
severe dysplasia v. carcinoma-in-situ at any anatomic site
CIN2 v. CIN3 of the cervix
Atypical melanocytic proliferation v. "early" melanoma
....you get the idea!