In December 2010, I was diagnosed with a tiny bit -- less than 1 mm -- of Gleason 6 (now Grade Group 1) prostate cancer. In six biopsies with more than 80 cores over nearly 13 years, that speck of cancer is all that has been found.
I have seen two urologists while on Active Surveillance (AS, or close monitoring of this cancer). One called my cancer "wimpy." The other said it was "the lamest cancer I've ever seen." I found these descriptors funny, and reassuring, as intended.
My urologists have never formally used the term "very low-risk" (VLR) prostate cancer. The term came in vogue around the time I was diagnosed, as the American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN), two leading guideline writers, adopted this nomenclature.
The idea was to separate those with VLR lesions from those with low-risk (LR) and vary the intensity of surveillance based on the amount of cancer present. VLR is essentially low-volume, low-grade prostate cancer. LR is higher-volume, low-grade prostate cancer.
According to NCCN, VLR is defined as:
- Grade Group 1
- PSA <10 ng/mL
- Fewer than three prostate biopsy fragments/core position, ≤50% cancer in each fragment/core
- PSA density <0.15 ng/mL/g
LR patients are the rest of the Grade Group 1 population.
All patients with LR and VLR are candidates for AS. But the VLR group can qualify for less intense monitoring, meaning fewer tests spread apart at longer intervals.
An LR patient might have a PSA every 3 to 6 months, a prostate magnetic resonance imaging (MRI) scan every year or two, and a targeted biopsy, as needed, every other year or farther apart.
As a new patient, I started out with PSAs every 3 months and annual biopsies, and after that my monitoring was reduced. I now have a PSA/Prostate Health Index test annually. I haven't had an MRI and biopsy in 6 years. I'm 75 and may never have another biopsy unless my PSA (around 5) rises significantly.
However, the categorization of LR prostate cancer is going through some changes. Last year, the AUA the VLR diagnosis and combined the VLR and LR groups into a single LR group. They're the "lumpers."
Meanwhile, the NCCN panel, composed of prostate experts from more than 30 centers of excellence, has stuck with the separate VLR and LR distinctions. They're the "splitters."
The lumper and splitter approaches have been staples in science since before evolutionist Charles Darwin began in the mid-19th Century.
James Eastham, MD, chair in 2022 of the AUA guideline committee and chief of Memorial Sloan Kettering's Urology Service, explained the AUA position: "The hope was that it would convey that low-risk as a general category should be managed with AS rather than saying, 'Well, there's this special group of LR patients who are really very low-risk, and those are the ones we should focus on.'"
"It was really a hope that we would promote to the medical community, mainly urologists, that active surveillance is the number one recommendation for men with LR prostate cancer, and that's what should be discussed with every patient with LR prostate cancer. And that would include, of course, the very low-risk patients."
Ironically, Eastham also serves on the NCCN's Prostate Cancer Panel. Yet, he supports the AUA position.
Kevin Shee, MD, PhD, a urology resident physician at the University of California San Francisco (UCSF), argues that the AUA made the right move to help all Gleason 6 patients who should be on AS, including those with high-volume, low-risk cancer. In March, Shee published in European Urology calling for the abolition of the VLR category. He and his colleagues reported that UCSF has diagnosed no VLR patients since 2018. He attributes this to the increasing use of MRI-targeted biopsies.
The splitter school sees it very differently.
Daniel Spratt, MD -- an NCCN panelist and chairman of radiation oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland -- said that in reality, prostate cancer presents a "continuous spectrum" from "ultra low-risk, whatever you want to call it" to ultra-high risk. "I tell my patients that it's like a speedometer, going from zero to 100. These cancers are not totally different biologically," he said.
Spratt said splitting the diagnoses is helpful in communicating differences to patients and also in conducting trials. "You can't just say, everybody come on a trial."
He noted the gradations of prostate cancer are applied to high-risk and very high-risk and to favorable and unfavorable intermediate-risk prostate cancers. In 2013, as a resident at Memorial Sloan Kettering Cancer Center, Spratt co-authored a that divided intermediate-risk into favorable and unfavorable categories. Patients with favorable diagnoses (Gleason 3+4=7 or Grade Group 2) qualify for AS.
Jonathan Epstein, MD, the Johns Hopkins pathologist who has been a leading figure in classifying prostate cancers, laid down the fundamental research on prostate cancer volume in the 1990s that led to the VLR approach.
He still supports the concept: "There is a difference prognostically between VLR and LR."
While UCSF has not seen any VLR patients in years, Epstein said they're still out there. He estimates that the Gleason 6 population actually is made up 50/50 of VLR and LR.
He said AUA may be blurring the lines between VLR and LR to try to help patients understand that they all qualify for AS so they avoid overtreatment.
Shee maintains that the use of VLR suggests the opposite and puts higher-volume LR patients at risk for more aggressive treatment.
Are you a lumper or a splitter?
Epstein said -- and, as a patient, I agree -- the VLR diagnosis can be reassuring to most men contemplating AS.
I think both sides would agree that better ways should be developed to determine which patients are at risk for advanced prostate cancer. It could spare men like me from the burden of biopsies and diagnosis of a wimpy cancer, which can include emotional distress and financial toxicity from a harmless lesion.
Shee said, "Our hope for the future is that patients with your amount of disease are not biopsied/diagnosed at all, and that with MRI and noninvasive testing, we can identify VLR patients without subjecting them to the pain, discomfort, and side-effects of biopsy."
Howard Wolinsky is a Chicago-based medical writer. He has written the blog, "A Patient's Journey," for 鶹ý since 2016. He is the editor of the Substack newsletter, .