Sunday, February 10, 2008

Prostatic Tubular Neogenesis - A letter to colleagues

Given that a priority of the medical profession is to alleviate pain, it is incumbent upon its practitioners to avoid using emotionally-laden terminology that causes just which it wishes to avoid, i.e., pain. The terms “cancer,” “malignancy,” and “tumor” and are firmly entrenched in our common socio-political vocabulary. Bringing one of these terms to consciousness has the effect of conjuring up a lethal adversary for which screening, early detection, and opposition with specific treatment is mandated.

However it has been increasingly clear for the past several years that most patients who are presently diagnosed with one of the above terms in relation to their prostate are at risk of treatment for which the cost in side-effects far outweighs any benefit of aggressive treatment.

The incidence of prostate cancer is presently four to five times its mortality. Sixteen percent of men will be diagnosed with CaP but only three percent will succumb to it. As both non-invasive (PCA3, TMPRSS-ERG) and invasive diagnostic advances (increasing number of biopsies per case followed by “triple” immunohistochemical stains) magnify our ability to detect abnormalities in an aging population, we will only increase the fear which leads patients and their physicians to make poor choices.

It is time to reconcile the discrepancy of the term that pathologists assign to a microscopic finding to the historical and practical significance of that term. The most common significant finding made by contemporary pathologists on prostate biopsies cannot be adequately described by “tumor” (Greek: swelling), “cancer” (from the crab-like extension), or “malignant” (threatening to life or tending to metastasize). I propose the terms “prostatic tubular neogenesis” (creation of new epithelial tubes or acini) and “potentially malignant” to better describe the microscopic findings that we have in the past labeled “adenocarcinoma” “cancer” “tumor” and “malignant.”

The pathologist discovering an abnormality perhaps only fractions of millimeters in length and present on a small fraction of prostate cores may indeed have uncovered evidence representing the tip of a much larger, more aggressive process. While even the smallest abnormal finding on biopsy may be an indicator of a much larger and possible life threatening process, it is more often an incidental findng that is best surveilled or ignored rather than aggressively extirpated. Although attempts to identify “clinically insignificant” prostate cancers have been attempted, the sampling error inherent in the biopsy procedure has precluded practical application. While small lesions lacking histological aggressiveness may indeed be “potentially insignificant” the indolent nature of their status cannot be proven until after a prostatectomy. A diagnosis of “adenocarcinoma” or “cancer” once issued on a pathology report and communicated by the urologist or patient and his family is never “insignificant.”

Criteria are evolving that allow for the active surveillance of the common microscopic neoplastic findings we identify. As these histological criteria (presently the number or fraction of involved cores, the length of the focus, the present of Gleason pattern 4 or 5) and increasingly molecular criteria (TMPRSS-ERG, hCAP-D3, AZGP1) evolve, we will better define which of our findings are potentially life threatening and which are indolent. Other factors such as patient’s comorbity, age, family history, genotype, and psychological biases will undoubtedly assist in the decision as to what course of action, if any, is in the patient best interest.

I suggest that the terms “cancer,” “adenocarcinoma,” “malignancy,” and “tumor” be avoided by on pathology reports unless there exists clear evidence of Gleason pattern 4, more than two cores are involved, or if total lesion length is more than 3mm. The term “tubular neogenesis” followed by an explanation, can better serve the discussion between physician and patient that must follow. As our understanding evolves, criteria for identifying life-threatening prostatic alterations on needle core biopsies in conjuction with serological or urine-based molecular assays, or new non-invasing imaging techniques will allow the more aggressive terms to be used without fear of inducing unnecessary medical intervention.

It is my hope that such a change in terminology may better serve our patients by fostering the educational discussions they must have with their doctors as they decide upon a course of action acceptable to both patient and clinician. We must continue to investigate the histologic and molecular prognostic variables that will be useful in separating out the minority of life-threatening prostatic neoplasms from the majority of indolent ones. In the meantime, let us see that our diagnoses are placed in context so that we are not accomplices in advising therapies that are worse than the disease. Primum non nocere.

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