Spontaneous remission in low-risk forms of prostate cancer


The issue of spontaneous remission of low-risk forms of prostate cancer came up yesterday during a meeting of Prostate Cancer International’s Active Surveillance Virtual Support Group (ASVSG).

Your sitemaster is aware of just one reported case of spontaneous remission in a high-risk form of prostate cancer. In the report of this case, Lee et al. describe a high-risk patient with apparent biochemical recurrence of prostate cancer after radical prostatectomy and a clear finding of a single, large, positive lymph node prior to and at the time of surgery. His PSA level immediately post-surgery was > 2.0 ng/ml and slowly climbed to 3.86 ng/ml. Because his PSA was climbing so slowly, he was given no further treatment. Then, at about 2 years post-surgery, his PSA level dropped into the undetectable range (< 0.1 ng/ml) and remained there. At 4 years post-surgery, his PSA level was 0.02 ng/ml and his serum testosterone level was within the normal range.

By contrast, it appears that spontaneous remission of low-risk prostate cancer in men on active surveillance may not be anything like as rare. The classic and very public example is that of Howard Wolinsky, who has been writing about the management of low-risk prostate cancer for several years now on the MedPage Today web site. Howard was initially diagnosed in 2010 with a very small amount of Gleason 3 + 3 = 6 disease in one of 14 biopsy cores. He has been on active surveillance ever since. In 2011, at an early follow-up evaluation, he had a positive MRI that showed two suspicious areas on his prostate. However, at a repeat, MRI-guided biopsy in early 2012, there was no sign of any cancer at all. Despite the fact that his PSA had risen to about 9 ng/ml by December 2013, when Howard had his fourth biopsy, there was still no sign of cancer on that biopsy. His PSA subsequently started to decline, and there has been no further signal indicating prostate cancer since.

But unlike the single case of spontaneous remission described above in the case of high-risk prostate cancer, Howard is far from being alone. Both Howard himself and another patient with a very comparable story were on the ASVSG call yesterday, and your sitemaster has come across  several other similar cases (although he hasn’t been counting). Perhaps he should have been.

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. 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).

However, as of today, it is beginning to seem like a really good idea for us 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 percent of all the men with very low-risk disease, like Howard? Or might it be 5 percent of all the men with low- and favorable intermediate-risk prostate cancer? We don’t currently have a clue.

What we do know is that if it is a significant and meaningful number of patients, these patients might be able to offer us greater insights into exactly why such spontaneous remissions occur, and that could be very important.

For those who are interested in reading more about spontaneous remission in cancer generally, try these two relatively recent articles by Eldridge and by Pukel. Your sitemaster is aware that spontaneous remission is an area of research interest at the National Cancer Institute, and he was under the impression that there was a small group of researchers trying to build a database of confirmable cases. However, so far he has been unable to identify that research team. One of the most widely held hypotheses is that such spontaneous remissions may occur most commonly when a patient’s immune system is stimulated by certain types of infection. This hypothesis was first proposed by the late Dr. Lloyd Old and it does correlate with other recent information about the use of immunotherapeutic approaches to cancer treatment (e.g., checkpoint inhibition and CAR-T). Dr. Old himself died of prostate cancer at the age of 78.