Speed of change in the management of prostate cancer

One of our regular correspondents (who lives in England) was recently told something rather interesting by the Consultant Urologist he sees in the UK. The gist of the Consultant Urologist’s comment was as follows:

The urologic oncology community is getting better at treating prostate cancer faster than your prostate cancer [i.e., the cancer of the patient in question] is getting worse.

This particular patient was diagnosed a while ago with favorable, intermediate-risk prostate cancer. He has been managing this on active surveillance (AS) for nearly 2 years since his actual diagnosis in 2016, but he had been  monitoring his PSA level since 2008 and had initially refused a 12-core transrectal biopsy in 2013. He appears to be in his mid to late 50s.

The patient in question has pointed out that, for men who are good candidates for AS and who are considering AS as an initial form of management for their prostate cancer, it is important to take into account not how progressive forms of prostate cancer are being treated today, but

  • How clinically significant and progressive forms of prostate cancer were being treated 15 years ago compared to today and
  • How clinically significant and progressive forms of prostate cancer are likely to be treated 15 years from now (should such treatment ever be needed)

We should also note that this particular patient (because of his occupation) has a sophisticated ability to assess risk/benefit decisions and a high level of statistical education. He is therefore relatively unusual in a couple of important ways. However, the point he brings to our attention is actually a very interesting one, so let’s explore it a little further.

If you had been a 62-year-old patient of Dr. Laurie Klotz in Canada in 2003 and you had just been started on active surveillance as a relatively “good” candidate for AS (PSA level 5.8 ng/ml; two positive biopsy cores out of 12, with 10% Gleason 3 + 3 = 6 in each of the two cores; a clinical stage of T1c; and a prostate volume of 49 cm3), you might well still be on AS today — or you might have progressed. But what were your other options back in 2003?

They would have included:

  • Open radical prostatectomy — because laparoscopic surgery, with or without a robot assistance was in its infancy
  • Relatively early forms of intensity modulated radiation therapy (IMRT), the older three-dimensional conformal radiation therapy (3D-CRT), and permanent seed-based, low-dose-rate brachytherapy — because the more sophisticated forms of radiation therapy available today (including proton beam radiation therapy, image-guided radiation therapy, sterotactic body radiation therapy, and high-dose brachytherapy), if available at all, were only available at a very small number of specialized or tertiary care institutions
  • Early forms of whole gland cryotherapy — which even then were known to have high risk for complications and side effects

In other words, by comparison with all the things that are available today, your choices would have been very limited.

Similarly, if we look at the options that would have been available to you if your initial treatment failed, those choices would have included:

  • Continuous and intermittent forms of androgen deprivation therapy (ADT) using an LHRH agonist with or without an antiandrogen like bicalutamide
  • Docetaxel + prednisone as first-line chemotherapy if you were metastatic and became castration-resistant
  • Other forms of late-stage therapy that could only relieve pain (e.g., mitoxantrone + prednisone and radioactive strontium injections)

Indeed, docetaxel + prednisone had only just been approved for the treatment of mCRPC. There was no sipuleucel-T (Provenge). There was no abiraterone acetate (Xytiga). There was no enzalutamide (Xtandi). There was no apalutamide (Erleada). There was no cabazitaxel (Jevtana). There was no radium-223 (Xofigo). And no one was going to tell you that even if you became castration-resistant with metastatic or non-metastatic disease you had a decent shot at several extra years of life.

With the exception of a few people like Dr. Klotz, most urologists would still have been telling you to have a radical prostatectomy promptly.

It is your sitemaster’s humble guesstimate that if the same relatively “good”, 62-year-old patient on AS (PSA level 5.8 ng/ml; two positive biopsy cores out of 12, with 10% Gleason 3 + 3 = 6 in each of the two cores; a clinical stage of T1c; and a prostate volume of 49 cm3), was to start on AS today, he might well still be on AS in 2033 or he might have progressed.

But his options — if he was to show signs of progression indicating a need for treatment — have changed radically:

  • There are something like a dozen forms of first-line therapy that can be applied today, including highly sophisticated forms of surgery and radiation therapy as well as all sorts of newer forms of treatment (from various types of focal therapy to things like Tookad-based VTE).
  • At least some of these forms of therapy can also be used more than once (e.g., HIFU) or they can be applied as second-line forms of therapy prior to any need for systemic, drug-based therapy.
  • Quite apart from basic, continuous, or intermittent ADT, we now have the six newer drugs named above, and we have learned a whole lot about how to use these more effectively.
  • Also … the use of MRI scanning to help to assess risk and eligibility for certain types of treatment is becoming commonplace.

What else might be available 15 years from now that goes above and beyond the things we can already imagine?

We can already imagine the potential possibilities of

  • CAR-T therapy for advanced forms of prostate cancer (if we can make it work)
  • Other new forms of immunotherapy (based on drugs like the PD-1 or the PD-L1 inhibitors and other new drugs currently in development)
  • Drugs for the treatment for specific subforms of aggressive prostate cancer (e.g., PARP inhibitors in the treatment of MSH and BRCA1/2 forms of prostate cancer)

But it is what we can’t really clearly imagine yet that is probably more likely. Relatively benign types of drug that can transform the way our immune systems work in relation to cancer, and that we could start taking as soon as there was any sign of progressive disease, might be among the most interesting. People are beginning to work on these — although not (yet) in relation to prostate cancer as far as your sitemaster knows.

4 Responses

  1. Great article! All men considering treatment instead of appropriate AS should read this!

    Here are a couple of additions to improvements in IMRT since 2003: now widespread knowledge that higher doses (such as 78 to 81 Gy) are needed, and growing use of rectal spacers such as SpaceOar to further lower an already very low risk of long-term rectal side effects.

  2. This was a very interesting post and well explained.

    There are many papers explaining various protocols by which to embark on active surveillance that can help the patient and his physician maintain close attention to prostate cancer cell activity, but the question always remains: which is the best one? My opinion is “patient attention” to his own understanding by personal research and study of these many protocols to then be able to discuss with his treating physician.

    From my own observations over these many years dealing with my prostate cancer, those patients who did much more than simply “follow the doctor’s orders” have fared the best in subsequent survival longevity. Both Jim Waldenfels and I fall into that category.

    Adding to the improvements cited by Sitemaster, we have newer forms of imaging that are more efficient in identifying location of cancer cell activity than the usual CT, PET/CT, MRI scans — among which are PET/CT imaging with radiotracers that include [11C]choline, sodium [11C]acetate, gallium-68 PSMA, and [18F]fluciclovine (Axumin).

    For the past twenty-two (22) years, following my own “recurrence” in 1996 — wherein usual imaging failed to identify cancer cell activity — my treatment for elevating PSA has been ADT medications that ran the gamut to include eventual abiraterone/Zytiga and enzalutamide/Xtandi; even with these more recent medications my PSA was showing new elevation.

    I was on the brink of chemotherapy when I learned the availability of 18F PET/CT imaging using the radiotracer fluciclovine available nearby at the University of Kansas Cancer Center Nuclear Radiotherapy Department. After all these years [18F]fluciclovine PET/CT “finally” identified the location of continuing cancer cell activity in my body. What a relief to learn I had no bone metastasis with head, chest, pelvic area and only very low but continuing activity in the area of my anastomosis from nearly twenty-six (26) years ago when my prostate gland was surgically removed in “open” surgery! Targeted “Edge” radiosurgery is being arranged and we shall see if my prostate cancer may be finally eradicated.

  3. Sitemaster – thanks for your apt edits.

  4. Chuck – That’s great news, and a fine example for others facing challenging recurrences! Wishing you the best!

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