Although the word “cancer” is often used to denote a single entity, cancers from different
parts of the body are unique in terms of their biology, prognosis, and treatment. What
may be less known to patients is that in some parts of the body, a single type of cancer
can have this same diversity. Nowhere is this more striking than with prostate cancer.
Prostate cancer ranges from tumors that are extremely slow growing (indolent) to those
capable of causing severe morbidity and death.
Whether a man has a prostate cancer characterized as indolent or aggressive is
primarily based on the grade determined by a pathologist, a physician who studies
tissue samples under the microscope removed during surgery or biopsy. A large part of
my career has been defining and correlating patterns of prostate cancer under the
microscope with how prostate cancer behaves. These different patterns result in the
stratification of prostate cancer into different grades, each with their own unique
microscopic appearance and prognosis. The grade assigned to the tumor by a
pathologist is critical for guiding therapy and determining prognosis.
The Gleason grading system used for prostate cancer ranges from grade 2 (most
indolent) to grade 10 (most aggressive). Expert prostate cancer pathologists and
clinicians, including myself, devised another grading system that is used in parallel to
the Gleason system. This intuitive patient-centric Grade Group system for prostate
cancer is composed of 5 grades.
Grade Group1 has an excellent prognosis and with men usually undergoing active surveillance; Grade Group 2 has a very good prognosis with rare metastases with some men undergoing active surveillance and others treatment depending on a host of factors; Grade Groups 3 and 4 have worse prognosis yet in most cases can still be cured with early diagnosis and treatment. Grade Group 5 (Gleason grades 9-10), which is what President Biden has, often presents with tumor that has already spread out of the prostate and is the grade most likely to result in death due to prostate cancer.
Prior to the reporting of President Biden’s aggressive prostate cancer, there was an
emphasis in the press on the more indolent nature of prostate cancer and the need for
active surveillance as opposed to definitive treatment, so as to avoid the side effects of
surgery and radiation. Over 50% of older men harbor cancer in their prostates with the
vast majority of these men eventually dying with but not of their cancer, never even
knowing they had prostate cancer.
There has been an ongoing debate as to whether low-grade prostate cancer should even be called “cancer”. The argument for renaming low-grade prostate cancer as “non-cancer” is that the fear of the word “cancer” could drive some men to overtreatment. Amongst the evidence to support Grade Group 1 as “non-cancer” was a study that I lead showing that Grade Group 1 (Gleason 6) cancer does not have the potential to spread though vessels to distant sites (i.e. metastasize).
However, most experts in the field of prostate cancer, myself included, think Grade
Group 1 prostate cancer should be called cancer. They look like cancer under the
microscope; can locally directly invade (without distant spread) out of the prostate; and
molecularly have many of the hallmarks of cancer. However, more importantly, from a
practical standpoint even with the most modern current tests available, there is a
significant risk of missing higher-grade cancer on biopsy.
Needle biopsy of the prostate samples a very tiny area of the prostate. Even though the biopsy shows Grade Group 1 cancer, elsewhere in the prostate could be higher grade, more dangerous cancer that needs treatment. If we called Grade Group 1 cancer not cancer, there would be a significant risk of mislabeling a patient with unsampled significant cancer. Patients would be told they don’t have cancer with a potentially greater risk of them not being followed as closely with repeat biopsies, repeat imaging, and follow-up visits. Also, this issue of renaming low-grade prostate cancer as non-cancer had greater relevance in
the past, where the majority of these indolent low-grade cancer were over-treated with
surgery or radiation.
However, currently, the vast majority of men with low-grade cancer in the U.S. are being followed on active surveillance, demonstrating that patients understand that they can be followed closely without immediate surgery or radiation even without renaming these indolent cancers as non-cancers.
President Biden’s situation calls to attention that prostate cancer can be very aggressive
and potentially lethal. His disease is at the other end of the spectrum of prostate cancer
virulence in comparison to low-grade prostate cancers followed on active surveillance.
It also raises conflicting issues relating to the diagnosis and treatment of prostate
cancer in older men. On one hand, there is the desire to not over-diagnose and over-
treat older men with a shorter life expectancy. Yet, there is a correlation with more
aggressive prostate cancer being more common in older as opposed to younger men.
With men living longer, there is also the risk that if nothing is done in older men to look
for prostate cancer they may present with advanced potentially incurable cancer. Some
experts in the field oppose looking for cancer in older men, arguing that it will still take several years before a man dies if he is diagnosed with
advanced prostate cancer.
However, dying of metastatic prostate cancer can be very painful and treatment can also have significant morbidity, severely affecting the quality of a man’s remaining life. There are guidelines, such as from the National Comprehensive Cancer Center (NCCN) that provide recommendations as to what age to stop screening for prostate cancer. These are guidelines, not requirements. It is a complex issue that should be tailored for the individual patient as to what should be done to diagnose prostate cancer at different ages of a man’s life.
Patients need to recognize that prostate cancer is not a single disease, with very
different approaches to each patient’s tumor factoring in multiple parameters along with
patient preference and their overall health. Knowing more about the spectrum of prostate cancer can help patients and their loved ones make more informed, collaborative treatment decisions.
Prostate Cancer is Not a Single Disease: A Pathologist’s Perspective
Jonathan Epstein, MD
Advanced Uropathology Center of New York
www.advanceduropathology .com
This article was submitted to WHN by Stacy Eichel, Marketing/Public Relations Coordinator, on belhalf of Dr. Epstein.
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