The APCCC in Basel, Switzerland: Day 2

The second day of the APCCC here in Basel ran for 10 hours and encompassed a total of six sessions, as follows:

  • A special session on the Movember IRONMAN registry project
  • Management of metastatic, castration-sensitive/naive prostate cancer
  • Management of castration-resistant prostate cancer (CRPC)
  • Side effects of treatment and their management
  • Bone and bone metastases
  • The future of APC management

The Movember IRONMAN registry project

Movember has funded the development and implementation of a 5,000+ patient registry study enrolling men with advanced forms of prostate cancer from a total of 11 different countries. Enrollment is possible if you have an advanced form of prostate cancer and if you live in one of the following nations: Australia, Brazil, Canada, Ireland, New Zealand, Spain, South Africa, Sweden, Switzerland, the UK, and the USA. The project has been running since 2017.

The study will collect detailed information about all enrollees, including things like the patients’ medical history and type of prostate cancer, their treatments over time, blood samples, and regular survey information. The primary goal is to see if collecting and analyzing this information can help us to better understand what causes prostate cancer, how to stop or slow its progression, and how to provide the best possible care and thereby optimize men’s quality of life over time.

To date, this registry has enrolled has enrolled 870 patients, of whom 792 remain on study. So there are still > 4,000 opportunities for readers with advanced forms of prostate cancer to participate.

Management of metastatic, castration-sensitive/naive prostate cancer

This was a complex session with seven different sessions and two discussion periods that encompassed multiple aspects of the management of metastatic, hormone sensitive prostate (mHSPC).

The first specific area of discussion was on how to test appropriately for serum testosterone levels in men on treatment for mHSPC. Current Canadian guidelines now state that serum T levels in men well managed on standard forms of ADT should be < 20 ng/dl. Your sitemaster specifically asked two of the experts about the need for monitoring of serum DHT levels in this setting. They advised your sitemaster that they no longer saw any benefit to this if the correct form of test for serum T was being carried out.

The next two presentations address the current and potential roles of surgery and radiation therapy to ablate the primary tumor in men with mHSPC. There seems to be no doubt that this is a wise step that can improve survival (at least with radiotherapy) in carefully selected patients. However, there is still a great deal of research needed into exactly how to select the correct patients, and into whether siurgical ablation of the primary is as effective as radiotherapy. The current suggestion seems to be that ablation of the prostate worked best for men with relatively low metastatic tumor burden … but other factors could be very important to this decision.

We were then challenged by three presentation on the general topic of “the best” ways to treatment with newly diagnosed, mHSPC. The only right answer to this question today is “each patient has to be evaluated individually”. Whether or not one is going to ablate the primary tumor, it is clear that the two basic forms of available treatment are docetaxel + standard ADT or abiraterone acetate + prednisone + standard ADT. Both these forms of therapy have been shown to benefit men newly diagnosed with mHSPC, and they each come with their pros and cons that may depend on everything from the patient’s tumor burden to his age and the genetic subtypes of his particular forms of prostate cancer. It seems likley to additional studies will be able to further segment patients into specific types of treatment based on definable characteristics, but this is going to take time.

This session was completed by a presentation on how to manage men  for the long-term who were on ADT alone or on ADT plus other forms of therapy but were still hormone sensitive. This is an area of evolving interest, and one should not assume that traditional forms of ADT and intermittent ADT are now outmoded for such patients. For the right patients, such therapies continue to be highly effective and relatively safe

Management of castration-resistant prostate cancer (CRPC)

From an “advances in medical care” perspective, this was probably the most interesting session of the day, in that it dealt wiith the many advances in the treatment of late stage disease — from the use of apalutamide (Eleada), datrolutamide (Nubeqa) and enzalutamide (Xtandi) in the treatment of non-metastatic CRPC (nmCRPC) to the use of drugs like lutetium-177 PSMA, the PARP inhibitors, and the PD-1 inhibitors.

Once again, while we have all these new agents available in the treatment of late stage prostate cancer, patients are going to need to appreciate that exactly which agents should be used when and in which specific patient types is going to need a lot of experience  and new data to work out. It is not even clear (yet) to what extent the ability to identify metastasis earlier through the use of better imaging techniques is going to change the definition of “non-metastatic”. Remember that in the trials of the above three drugs in the treatment of nmCRPC, nmCRPC was still being defined by the absence of metastasis on a bone and/or a CT scan.

Incidentally, at this meeting, Dr. Eric Small — half jokingly — described apalutamide, enzalutamide, and darolutamide, when used in the treatment of nmCRPC, as “SPA drugs” (based on the names of the trials that proved their value prior to chemotherapy: SPARTAN, PREVAIL, and AFFIRM). Ther term seemed to catch on, so don’t be surprised if you hear your doctor, some time in the future, refer to these as the SPA drugs.

Everyone is looking forward to the potential offered by new drugs such as the PARP inhibitors and the PSMA targeted agents (e.g., lutetium-177 PSMA), and there seems to be no doubt that these will be coming to market, but we were also reminded that new form of combination therapy using agents like sipuleucel-T and permbrolizumab earlier in therapy also present opportunities to be explored.

Finally, there was discussion of the treatment of the so-called “neuroendocrine” forms of prostate cancer, where drugs like carboplatin clearly have a potential role. The speaker was at pains to point out, however, that a whole bunch of slightly differentv types of later stage and other prostate cancers had become lumped together under the somewhat inappropriate term “neuroendocrine”, and that we still needed to find better terminology for this set of prostate cancers.

Side effects of treatment and their management

This was perhaps the most disappointing session of the day. Speakers reviewed and discussed options for the treatment of erectile dysfunction (and its consequences), incontinence, hot flushes, metabolic changes (e.g., weight gain, etc.), fatigue, cognition and dementia, etc. However, there is really minimal new knowledge in any of these areas. It appears as though in the hurry to find new and better types of treatment for advanced disease, the abIlity to alleviate the side effects and complications of all the available treatments has become an afterthought.

If there was one clear piece of new information in this area, it was that physicians and patients needed to be vary cautious about the idea that ADT and other forms of late stage therapy necessarily were associated with problems of cognition and dementia. There seems to be increasing evidence that if you divide patients into those with a significant risk for dementia and those who are not, this can explain much of the apparent onset of dementia without any reference to added risk because of ADT. However, this does not mean that ADT doesn’t have impact on cognitive function over time.

Bone and bone metastases

Protection of patients bones from unnecessary fractures is a key component of the management of advanced prostate cancer, and this session dealt carefully with this important topic.

There appears to be a growing consensus that not all patients on ADT necessarily need to be on antiresorptive therapy with drugs like zoledronic acid and denosumab. Rather, what is important is to be monitoring and testing all such patients for their bone density and risk for fractures and implementing antiresorptive therapy at an appropriate time. It was also made very clear that in the opinions of most experts, exactly which agent was being used was relatively unimportant.

On the other hand, for patients who are being treated with a combination of drugs like ADT and one of the newer androgen receptor blockers (abiraterone, enzalutamide, etc.), the need to simultaneously initiate antiresorptive therapy to protect against fractures appears to be a priority. The combination of traditional forms of ADT with the newer agenst appears to come with not only heightened risk for fractures, but also heightened risk for mortality associated with such fractures.

The future of APC management

This final session of the day was appropriately initiated by a British patient — Robin Millman — taking about patients’ “wishes”  for progress in the management of prostate cancer.

An issue that Mr. Millman emphasized several times in his short presentation was the need to address the quality of life and the psychological issues that so impact the prostate cancer patient community (and their family members). Unfortunately, not one of the following six presentations by physician-scientists addressed this set of priorities at all. It appears to your sitemaster that the patient community is going to need to push much harder for research into the areas of quality of life and psychological factors in the management of prostate cancer. It is all very well to be adding months and years to patients’ lives through the development of fascinating new drugs and prognostic techniques associated with better imaging methods, but what most patients want more than anything is to be able to enjoy those additional months and years of life and to be able to escape some of the debilitating side effects and complications of therapy if this can be made possible.

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