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Pathologist's View On Prostate Cancer Grey Zone: 'What Do My Numbers Mean?'

By Dr. Michael Misialek
Guest Contributor

We don't like to admit it but cancer is rarely black and white. Increasingly a cancer diagnosis means living in a murky morass of constantly reassessing risk.

Here's one man's story of living on that precarious line. His saga, seen through a pathologist's filter, illustrates the uncertainties surrounding prostate cancer. And, as the number one cancer in men, it is increasingly becoming a familiar story for many. Questions like, 'What do my numbers mean?' 'Should we treat or not?' and if so, 'Which treatment is best for me?' inevitably arise.

Mr. B. is a 64-year-old man who was found to have an elevated PSA four years ago on his routine physical exam. Obviously, prostate cancer was the first thought that came to mind, particularly since his father had the disease. What he soon learned is that prostate cancer is a complex diagnosis — one that requires the careful integration of the physical exam, biopsy results, radiographic studies and lab results.

And, of course, it's a diagnosis that comes with many decisions and choices; choices that depend upon understanding the grey zone of medicine. Prostate cancer is rarely clear cut. As much as numbers like the PSA and Gleason score (the sum of the two most predominant grades in a patient’s tumor) guide diagnosis and treatment, they also contribute to the uncertainties on the best course of action.

When Mr. B’s elevated PSA was first detected, his primary care physician referred him to a urologist at Newton-Wellesley Hospital. His prostate was normal on physical exam and they elected no biopsy at the time. Over the next couple of years the PSA slowly continued to rise, still with no change in his physical exam. Last year a biopsy was done and was negative. No cancer, a relief. What was found was some inflammation. Could this have contributed to the rise in PSA? It certainly could have, but a negative biopsy did not rule out cancer. The journey of watching numbers continued.

This year Mr. B.'s PSA rose yet again, and his urologist ordered an MRI which was negative. Mr. B. underwent another biopsy. (Not an easy process since he takes the blood thinner Coumadin and any invasive procedure needs to be carefully coordinated with stopping and restarting this medication.) The biopsy is also uncomfortable: his first biopsy involved six needles, but this time it was twelve.

The slides came to me. I put them on my microscope and carefully studied each of them. As I scanned at low magnification I found two tiny foci of abnormal glands which qualified for a diagnosis of cancer.

But it was only present in two of the sites and extremely small — 1 mm and 2 mm — literally not much bigger than the head of a pin.

Gleason’s original drawing illustrating the grading of prostate cancer. (Courtesy)
Gleason’s original drawing illustrating the grading of prostate cancer. (Courtesy)

The next challenge then was to grade the cancer. Important decisions about treatment, and more, depend on knowing the Gleason score. There's a lot riding on the pathologist’s diagnosis. As one can see from Gleason’s original drawing, the cutoffs between grades can be subtle. Mr. B.’s cancer was on the border between a Gleason grade 3 and 4, right in the grey zone. The Gleason score is calculated by the two most frequent patterns seen in the biopsy. Thus his Gleason score could be interpreted as a 3+3 (6) or a 3+4 (7), seemingly small differences, but one with big consequences.

A patient with a low volume Gleason score 6 cancer will generally be recommended active surveillance, defined as careful observation with regular exams, PSA and biopsy, but no treatment. A score of 7 will often begin serious discussion about treatment. Active surveillance is less likely to be offered. Such treatments may include surgery, radiation (external beam, seeds) and cryoablation. At the recent American Urological Association meeting, one of the hot topics was on active surveillance in low volume score 7 patients.

As a pathologist, I frequently consult my colleagues for opinions on challenging cases. The more eyes the better. I turned to my colleagues to weigh in. Dr. Michelle Hirsch, a pathologist at Brigham and Women’s Hospital who specializes in genitourinary pathology, says consistency and precision are some of the most challenging aspects of diagnosing and grading low volume prostate cancer.  Experience builds this level of accuracy.

Mr. B. listened intently to my description of what I saw under the microscope. He felt even more relieved knowing his cancer had favorable characteristics. He is like many patients these days, asking many questions, doing their own research and accessing their labs online. He watches his numbers.

Perhaps the most controversial topic is the benefit of routine cancer screening by use of the PSA test. Screening for cancer should be a no-brainer, right? But it's not. Interestingly, the pathologist who discovered PSA is a firm opponent of routine screening.

Cancer detection involves more than PSA. A patient’s symptoms, digital rectal exam, family history and imaging findings are equally important. It is this distillation of all the clinical factors that informs clinical decision-making.

These days, a multidisciplinary team takes care of Mr. B., including experts in urology, pathology, radiology, hematology oncology and radiation oncology. Our team meets regularly to discuss patients like Mr. B. The College of American Pathologists recently published a report on the value of this collaborative effort in the care of prostate cancer patients.

You may never meet me, the pathologist, but I am a major factor in your care plan. Treatment begins with a pathologist’s diagnosis.

Mr. B. and his wife are content with the decision to pursue active surveillance. He will undergo regular PSA checks, imaging and biopsy. He will be watching his numbers. If anything changes, he knows he has a full armamentarium of treatment options available.

His story illustrates what for many is the new normal — the grey zone of medicine and the uncertainties in prostate cancer. More and more doctors practice in this realm as our patients pursue their lives.

Dr. Michael Misialek is Associate Chair of Pathology at Newton-Wellesley Hospital and Assistant Clinical Professor of Pathology at Tufts University School of Medicine.

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