Getting Back to You: Responses to Comments on Cancer 2018

Doc Gumshoe follows up...

By Michael Jorrin, "Doc Gumshoe", October 30, 2018

The plan was for Doc Gumshoe to fix his gaze on the hype around Delta 8 as the ultimate banned cancer cure, which he will definitely get around to.   But the volume of comments and queries that “Cancer: The Lay of the Land in 2018” was such that I have little choice but to attempt to answer them to the best of my ability.   As of last count, there were eighteen distinct requests for further sleuthing, most of them suggestive and interesting, which tells me that the denizens of Planet Gumshoe are keenly interested in what’s going on in that particular area of medicine – not only how it affects their health, but their wealth and happiness.

Treatment of recurrent prostate cancer

The lead-off question here is how was the prostate cancer initially diagnosed and treated.   An exceedingly disquieting trend in the past few years is that fewer men are being diagnosed with prostate cancer, but that there is a considerable increase in the incidence of metastatic prostate cancer.   This emphatically does not mean that the disease is getting more severe.   It means that, largely because of the recommendation of the U. S. Preventive Services Task Force, fewer men are opting for the prostate-specific antigen test as part of their annual health check-up, therefore fewer cases of cancer are being identified and diagnosed – not that the incidence of prostate cancer is diminishing, only that its diagnosis is diminishing.   And that means that more cases of prostate cancer are being diagnosed at a later and more dangerous phase.   That could lead to metastasis of the cancer to a distant site or to local recurrence.   

Recurrence of prostate cancer can occur even if the prostate gland itself is removed surgically.   This can happen if cancerous cells have escaped from the capsule and invaded the surrounding tissue, in which case a local recurrence of the cancer might emerge even if the gland is gone.   When the prostate gland is excised by open surgery, the surgeon is scrupulously careful to make sure that the margins – the tissue around the prostate – are clean.   This is less possible when the treatment is radioactive seed implantation.

The most likely destination for cancer cells that have survived the initial treatment is the lymph nodes in the surrounding area, and the next most likely location is the bones.   A treatment option that is frequently employed in the event of recurrence is androgen deprivation therapy, since the growth of prostate cancer cells is stimulated by testosterone.   To this end, patients are given treatment that aims to block the effects of androgen, such as a luteinizing hormone-release hormone antagonist (LHRH) – for example, Pfizer’s Xtandi (enzalutamide) – an androgen antagonist.   Another drug in this class is Johnson & Johnson’s Zytiga (abiraterone).   Hormone therapy may be combined with some form of chemotherapy, such as drugs that inhibit the growth of blood vessels to the cancer cells (angiogenesis), those that inhibit cancer cell replication, or checkpoint inhibitors.   And in some cases, surgical castration has been employed.  

Recently, drugs in a class termed PARP inhibitors have been successfully used to treat recurrent prostate cancer.   These are inhibitors of the enzyme poly ADP ribose polymerase (PARP), which cancer cells rely on for growth and replication.

For example, just a few days ago the FDA granted a PARP inhibitor, rucaparib (Rubraca, from Clovis Oncology), breakthrough therapy designation for single-agent use in adult patients with metastatic prostate cancer following at least one androgen receptor-directed therapy and chemotherapy to prevent cancer cell replication.   That language makes it sound like a highly limited indication, but in reality it would describe almost all patients with prostate cancer that had escaped the prostate gland itself and lodged elsewhere in the body.       

Another agent in that class is AstraZeneca’s Lynparza (olaparib), which, when given in combination with J & J’s Zytiga, extended survival in patients with recurrent prostate cancer significantly longer than Zytiga given as monotherapy.

The objective of prostate cancer treatment should obviously be to catch it early and kill it quickly, so that the treatment of recurrent or metastatic prostate cancers is infrequent.   A treatment mode that appears to accomplish this effectively is termed “active surveillance.”   This practice differs from “watchful waiting,” in that it entails further regular PSA testing and repeat biopsies.   That strategy has recently been confirmed by a report at a recent AUA meeting which was based on a retrospective review of about 2,200 patients who had entered active surveillance between 1995 and 2016 at Mass General Hospital and the Sunnybrook Health Sciences Center in Toronto.   Of those patients, 432 were under age 60 at the start of active surveillance.   Their median PSA level was 4.6 ng/dL, which is at the low end of the range indicating the likely presence of a cancerous tumor in the prostate gland.   Almost all the men – nearly 98% – had a Gleason score of less than 6, pointing to a fairly early stage cancer.

The big news is that after follow-up – which in some cases went on as long as 22 years – not one single man in that group died of prostate cancer.   After five years of follow-up, 131 of those 432 men opted for some form of definitive treatment.   The most common reason was evidence of pathologic progression based on repeat biopsies, which led to definitive treatment in 88 men.   An additional 24 men decided to have definitive treatment based on rising PSA levels, and 15 men made that decision for other reasons.   The most frequent form of definitive treatment was radical prostatectomy, chosen by 82 men in this cohort.   But, to repeat the main take-away, in that group of 432 men who had gotten a diagnosis of prostate cancer, not one died of the disease, which had in those individuals been identified and treated in time.      

Qbiotics, from North Queensland, Australia

I’ll confess that this outfit had never emitted so much as a blip on my radar screen.   Qbiotics appears to be primarily focused on animal health, but they are making a transition to human health product, where obviously greater financial rewards are to be found.