Prostate cancer and its management: where we are at now

A relatively long article in the June 21 issue of US News & World Report discusses a series of topical issues related to the diagnosis and management of prostate cancer, including:

  • The “slow down” in the decline of the prostate cancer-specific mortality rate since 2013 (although it still has been dropping and was < 19 deaths per 100,000 in 2015)
  • The increase, between 2010 and 2014, in the numbers of men being diagnosed with metastatic prostate cancer  (from 6 per 100,000 in 2010 to 8 per 100,000 in 2014)
  • The recently approved change in the USPSTF guidelines for prostate cancer screening
  • The increasing numbers of prostate cancer patients whose first-line form of management is now either active surveillance or watchful waiting (consequently reducing risk for unnecessary over-treatment)

The article is based in part on prostate cancer data provided in the National Cancer Institute’s Annual Report to The Nation on the Status of Cancer, Part II: Recent Changes in Prostate Cancer Trends and Disease Characteristics, published in the July 1 issue of the journal Cancer (and no, your sitemaster has not yet had a chance to read through this dense, 14-page article,  which is available in full on line for those who are interested).

One of the things that continues to annoy your sitemaster, however, is that that the article in US News & World Report seems to use the terms “active surveillance” and “watchful waiting” as though these are near to interchangeable terms with the same implications,  and they are very definitely not. So, once again, let us be clear:

  • Watchful waiting is a passive technique that can be used to manage men with prostate cancer whether they have localized, advanced, or metastatic forms of prostate cancer if they have no evidence of symptoms; if they are unlikely to benefit from immediate treatment of any type; or if there is a high probability that they are not actually going to die from their prostate cancer. The “classic” type of patient suitable for watchful waiting would be a man in his late 70s who has been diagnosed with prostate cancer but who has multiple co-morbid conditions (diabetes, cardiovascular disease, etc.) that can not be well controlled and who has a life expectancy of 5 years or less. Such men are normally given regular PSA tests and clinical exams (maybe annually) to make sure there has been no significant change in the status of their prostate cancer, and treatment would only normally be given to relieve symptoms of their disease on progression.
  • Active surveillance (sometimes also known as active monitoring) is a proactive technique that is increasingly commonly being used to manage men with relatively low-risk forms of prostate cancer that are confined to the prostate; that might never progress to become clinically significant; or that will still be treatable later, with curative intent, should there be signs of disease progression. In other words it is a technique used to defer active, curative treatment until it becomes evident that such treatment is needed, and thus avoid immediate but potentially unnecessary over-treatment (and the consequent complications and side effects of such treatment) until treatment is actually necessary. The “classic” type of patient suitable for active surveillance might be a man in his early or mid 60s who has been diagnosed with a PSA level of < 10 ng/ml, a Gleason score of 3 + 3 = 6 (i.e., Grade Group 1), a clinical stage of T1c, and no symptoms of prostate cancer. Such a patient might never need treatment at all, or his disease might progress after some period of time and curative treatment could then be given. In the interim, the man’s quality of life would have remained high.
  • Conservative management is a term that can be used appropriately to include both watchful waiting and active surveillance because it simply means monitoring with no immediate treatment.

The failure to use these terms consistently and accurately is only helping to further confuse men who are newly diagnosed with prostate cancer. If a doctor tells the patient they he or she thinks that they can just “watch” his prostate cancer, what is he actually telling the patient? And we are still working out just how aggressively individual men on active surveillance need to be monitored, because it depends on a whole spectrum of factors that may impact the frequency of testing — and the types of test that need to be done.

It is relatively straightforward to just monitor a patient who is on “watchful waiting” using occasional PSA tests (unless something else becomes necessary). It is much more complicated to manage a man well on active surveillance because the spectrum of useful tests is much greater and most patients on active surveillance will want to avoid any prostate biopsy that isn’t actually necessary. Quite apart from the fact that it is often uncomfortable and distinctly dehumanizing for the patient, every biopsy comes with some degree of risk for complications and side effects in and of itself.

It may take us many more years to really work out how best to manage men on active surveillance in ways that will maximize the length of time they can stay on AS and minimize their risk for disease progression. And there is no doubt that the appropriate form of AS will vary depending on specific types of patient and their precise clinical situation. But — in the interim — can we please at least get some standardization of the terminology use to describe the differing forms of care?

And now, to return to the “slow down” in the decline in the prostate cancer-specific mortality rate. …

We are probably going to need another major scientific “leap forward” in order to re-accelerate the decline. We had major steps forward from 2000 through to 2014 and 2015, with multiple new drugs and new drug combinations being used to treat advanced forms of prostate cancer; greater skill and superior technology in the use of standard treatments like surgery and radiation therapy; and completely new forms of treatment that we are still learning how to best apply. However, the next great step forward will probably be learning how to enhance our immune systems to work better against advanced forms of prostate cancer. CAR-T cellular therapy and drugs like pembrulizumab (Keytruda) and nivolumab (Opdivo) are revolutionizing the treatment of some forms of cancer (e.g., aggressive forms of melanoma and lung cancer and some of the hematologic cancers). Unfortunately, to date, these forms of therapy don’t seem to have been having the same levels of impact on advanced forms of prostate cancer … but the dsoor is now wide open to new opportunities in the field of immuno-oncology, and it seems highly likely that we will find new immuno-oncologic treatments that will work well against prostate cancer in the near future.

Last but not least … There is still an urgent need for a form of non-invasive test that can tell us, with a very high degree of accuracy:

  • Whether a man has prostate cancer, as opposed to other possible prostate-related conditions like BPH or prostatitis
  • The risk level of that prostate cancer if he does indeed have prostate cancer

It is high time that we identify, develop, and put into standard use tests that could minimize the need for use of the PSA test (which really only tells a doctor and his patient that there is “some sort of prostate-related problem”) and the prostate biopsy (which was once a huge advance in the ability to judge a patient’s level of risk, but has become an enormous burden for tens of thousands of men with prostate cancer who are at risk for multiple biopsies over time).

One Response

  1. As a volunteer mentor to men worldwide over the internet, one of the primary concerns of newly diagnosed men who have not yet had a biopsy is the fear of that biopsy, the discomfort they “might” experience, the concern they will experience infection from biopsy needles. They are searching for biomarkers or imaging that is sensitive enough to identify the absolute presence of prostate cancer development. So, yes, we would certainly hope that with continued research and trials we will one day come upon those specific procedures that will once-and-for-all eliminate these concerns.

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