Can prostate cancer resolve itself?

medpagetoday.com - Mystery! The Vanishing Prostate Tumor | MedPage Today

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Cancer specialists are comfortable with the terms partial remission and complete remission when patients undergo some sort of aggressive therapy such as radiation or chemo. But the concept of spontaneous remission is more problematic, especially with low-risk prostate cancers in patients like me on active surveillance (AS) who have had no treatment at all. Back in May, Michael Scott, a patient advocate and layman with loads of expertise with prostate cancer, went out on a limb to suggest in his blog that spontaneous remission was real and worthy of the attention of serious researchers. Scott, founder of Prostate Cancer International and its Active Surveillance Virtual Support Group, mentioned my case and that of a man whose name he couldn't recall. I asked other men in two virtual support groups for men on AS if they had experienced spontaneous remission. James Simms, 72, a retired banker from Tampa, was the only one to reply. As it happens, he had described his case at Scott's group. Simms and Scott gave me a new perspective on what might have happened with my "lame" cancer, as my urologist calls it.

My case

I was diagnosed with a sliver of Gleason 6 in a single core in a blind biopsy in December 2010, and two tiny suspicious lesions were disclosed in a multiparametric magnetic resonance imaging scan a few weeks later. Follow-up biopsies in 2012-2016 showed no sign of cancer. Likewise, a follow-up MRI in 2016 revealed no lesions. I was cancer-free as far as the radiologists were concerned. So my cancer potentially disappeared sometime in 2011, though that was not acknowledged at that time.

My urologist, Brian Helfand, MD, PhD, of NorthShore University HealthSystem in Glenview, Illinois, joked last year that if my PHI (Prostate Health Index) were any lower, I wouldn't have cancer at all. Was he inadvertently on to something?

I have asked Helfand and my previous urologist what had happened to my cancer. Did it just go away -- albeit in a less dramatic fashion -- than the case of St. Peregrine, a 14th-century priest, patron saint of cancer patients, whose ulcerated cancerous leg healed the night before he was to undergo an amputation? Had I experienced a spontaneous remission or regression?

Such cases involving all sorts of cancers, confirmed in biopsies and advanced imaging, are sprinkled throughout the medical literature. My urologists told me cancer still was lurking somewhere in my prostate, a dark passenger too small to find. For the record, my PSA, which had reached a peak of nearly 9 ng/mL in 2013, has dropped and been stable for about six years, settling in at around the upper 4s and low 5s. The results produce a flat-line graph. This phenomenon could not be explained. Otis Brawley, MD, former medical director of the American Cancer Society, suggested my slides had been switched. (Something like that happened in a study of pharmacogenomics for which I volunteered at the University of Chicago.) A radiologist theorized that the inflammation brought on by a biopsy in 2010 might have activated an immune response that gobbled up my mini-cancer.

Another theory was a biopsy scooped up my only trace of cancer. Who knows?

Simms' case

James Simms' urologist calls him an AS pioneer. In fact, he was among the first AS patients in the U.S. He was diagnosed with two cores with Gleason 6 at 10% or less. He went on AS in November 2006. He had three blind biopsies from November 2006 to November 2010. Each showed the presence of Gleason 6 cancer. Multiparametric MRI scans he had in October 2017 and March 2019 suggested a growing presence of cancer based on his PI-RADS scores (Prostate Imaging Reporting and Data System) of 4 and 5, respectively, These are considered highly suspicious and a biopsy is indicated. But then Simms experienced a sudden improvement, a St. Peregrine moment to some. This April, Simms underwent a follow-up, a 16-needle guided biopsy that showed no cancer. "NO CANCER! Regression in prostate cancer is seemingly rather rare," he said.

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What might have caused his remission? Simms speculated, "Two UTIs (urinary tract infections), a swollen testicle and abscess from September through December 2018 kicked my immune system into action." In August, Trushar Patel, MD, Simms' urologist at the University of South Florida, ordered a new biopsy with and without a gadolinium-based contrast agent. More good news. Simms got a PI-RADS 2. "This lesion has gotten smaller, and it may be prostatitis we're dealing with!" he said. "In Jim's case, I think he had an infectious process that was mimicking cancer progression on MRI," said Patel. "This case highlights the limitations of MRI in distinguishing cancer from benign pathology. Unfortunately, we cannot prove that his immune response put his cancer into remission. We could have simply missed his cancer focus on the prior biopsy, as his cancer was small and can be difficult to localize." Patel and Helfand told me the same thing: spontaneous remission is impossible to prove unless the prostate is removed and reexamined as a whole specimen pathology. For the record, no one on AS is volunteering for that. Meanwhile, Scott checked the medical literature and found a single case of spontaneous remission in a man with advanced prostate cancer and none in men with low-risk disease. Still, he said he personally has encountered a number of such cases, including my "classic and very public case" described in this column in MedPage Today. Scott theorizes there likely is nothing in the literature about such cases because AS is so new in the U.S., available only since the first decade of this century. "It makes perfect sense that prior to the modern 'active surveillance era' reports of cases of spontaneous remission of low-risk prostate cancer would have been non-existent. Prior to the availability of the PSA test, most such patients would never have been diagnosed at all," he said. "After the availability of the PSA test in the 1980s, and for the following 20 or so years, nearly every man who was diagnosed with low-risk prostate cancer was told he needed immediate treatment, and so there was no chance that he could have gone into spontaneous remission because his cancer had been eliminated (albeit, in many cases, unnecessarily)." The idea of spontaneous remission for low- to intermediate-risk prostate cancer received mixed reactions in the medical communities involved with caring for men with prostate cancer, ranging from possible to impossible.

Pathologists weigh in

Jonathan Epstein, MD, director of surgical pathology at Johns Hopkins Hospital in Baltimore and a leading provider of second opinions on prostate exams, said in a terse email: "[Spontaneous remission] does not happen in prostate cancer. [Prostate cancer is] just a small cancer that on repeat biopsy can be easily missed." Lester Raff, MD, MBA, medical director of the laboratory at UroPartners in suburban Chicago: "I have not had much exposure to the concept of spontaneous remission. I am a little hesitant to accept it. It would mean 1) that the tumor stopped growing and 2) all malignant cells died. I have not seen evidence of that total tumor necrosis without some active intervention, such as radiation." "The question I always have with such apparent cures is the accuracy of the initial diagnosis," Raff continued. "Lesions diagnosed as Gleason Grade 2 carcinoma on prostate biopsy 15 years ago might not be classified as cancer today. The usage of special stains has also made it possible to diagnose as benign some lesions that were once thought to be malignant."

Urologists too

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Helfand: "While it is a good thought -- I do not know of anyone who has spontaneous remission. There are many examples where someone was diagnosed and treated historically and was not found to have disease in surgery pathology. But this was thought to be such a low-volume disease that the pathologist couldn't find it. I am not convinced that a tumor resolves -- especially a low-risk tumor that invoked little immune response. But who knows? Anything can be possible." Laurence Klotz, MD, the University of Toronto urologist who pioneered active surveillance in 1997, commented in a 2018 lecture that spontaneous remission is well recognized in breast cancer and probably applies to prostate cancer as well.

And now radiologists

Speaking about all types of cancer, Joel Dunnington, MD, who recently retired as professor of diagnostic radiology at MD Anderson Cancer Center In Houston: "There are some spontaneous remissions. But these are very rare without treatment. This probably just indicates a very good immune system that is actually doing what it is supposed to do." Ari Goldberg, MD, PhD, medical director of MRI at Loyola University Medical Center in Maywood, Illinois, said he has seen a handful of men on active surveillance who would qualify as having experienced spontaneous remissions from an imaging standpoint. He added: "Playing the devil's advocate, the first thing you say is, 'Well, how do we know that the first diagnosis was correct?' We tend to think that the pathologist is always correct, but when the pathologist said, 'Okay, that's Gleason 6 or 7,' etc., was he or she correct? And now the MRI doesn't show the same thing and a targeted re-biopsy doesn't show the cancer. What else should we call it aside from remission?" Scott said it's time to start carefully tracking the incidence of apparent spontaneous remission of prostate cancer in men on active surveillance. "Just how many of these men are there? Is it 1% of all the men with very low-risk disease, like Howard? Or might it be 5% of all the men with low- and favorable intermediate-risk prostate cancer? We don't currently have a clue." Maybe there are lessons that can be learned from cases of suspected spontaneous remission that can help other men with prostate cancer. Simms said: "Over the last several years I participated in the Blessing of the Sick at St. Mary's Catholic Church on the last Sunday of the month! Did I have a prostate cancer miracle? Was St. Peregrine operating in Tampa Bay? If nothing else, this experience calls into question those Facebook Fear Mongers who belong to a 'Prostate Cancer Surgery or Else' support group especially for low-grade cancer." As for me, I retired from religion long ago. Whether my case is considered spontaneous remission or not, makes little difference. As I head into my tenth year on AS, I would be satisfied if my PSA remained stable and I had as few as possible MRIs and biopsies in the years ahead. That would rank as a miracle of sorts in my book.

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medpagetoday.com - Mystery! The Vanishing Prostate Tumor | MedPage Today

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