THE "NEW" PROSTATE CANCER INFOLINK

So in this series of reports on what happened at the 3rd Advanced Prostate Cancer Consensus Conference (APCCC) in Basel, Switzerland, we will not be trying to get into detail about exactly what data got presented each day.

Rather, our goal will be to try to communicate information about how the management of advanced prostate cancer is becoming much more complex as we move from treating basic forms of advanced disease (node-positive or metastatic disease) to treating advanced prostate cancer using “precision” forms of medical care.

Sessions today (Thursday) dealt with the following four key topic areas:

• Molecular biomarkers and novel imaging in advanced prostate cancer
• Node-positive prostate cancer (N1 but M0)
• PSA recurrence after radical local therapy and oligometastatic prostate cancer
• Regional care (demographic and environmental factors)

Molecular biomarkers and novel imaging

The first of the topics in this session focused on the roles of genotypic (hereditary DNA testing) and somatic (tumor DNA testing) sequencing in the care of men with advanced prostate cancer and the need to be able to both test for specific genetic markers (like the BRCA1/2 and other genes) and then understand how useful this information is, currently, in making decisions about how to treat men with such biomarkers.

It was clear from the presentations and the discussions that considerable progress is being made in this field, but also that we are still early in the learning process. The bottom line as far as your sitemaster could tell from the discussions was that there was a general consensus among experts that all men with high-risk and/or metastatic forms of prostate cancer should at least ask their doctors about having molecular testing of their their somatic (tumor) DNA or their genotypic (hereditary) or best of all both. However, the ability of the average urologist or oncologist to be able to interpret the results of such tests remains low, and it is crucial to have the results of such tests evaluated by a molecular pathologist if one is to be able to actually use such information to make treatment decisions.

The second of the topics in this session was devoted to the evolving role of gallium-68 PSMA PET/CT scanning in identification of risk for and making decisions as to the treatment of high-risk forms of prostate cancer — and in particular the precision with with this new form of PET/CT scan can determine the location of cancer tumors prior to definitive first-line therapy and/or in patients with recurrent disease after first-line treatment.

Once again, the general consensus among the experts was that gallium-68 PSMA PET/CT scanning has taken our ability to identify high-risk lesions at relatively low PSA levels to a whole new level (beyond that available with the Axumin PET/CT scans). However, it was also carefully pointed out that our ability to know how to interpret the data from such scans was still in evolution. Gallium-68 PMSA PET/CT comes with false negatives and false positives. We also know that there is a significant set of risks for over-treatment among some men with positive gallium-68 PSMA PET/CT. And, on top of that, the quality of the CT scan element of the gallium-68 PMSA PET/CT scan data can vary significiantly from ceneter to center and trial to trial.

Node-positive prostate cancer (N1 but M0)

We are increasingly having to face up to the reality that historical “node-positive” prostate cancer can be subdivided into a series of subcategories:

• Clinically node-positive prostate cancer based on data from classical forms of imaging (e.g., mpMRI scans)
• Clinically node-positive prostate cancer based on data from new forms of imaging (e.g., Axumin-based, gallium-68 PSMA-based, and [¹¹C]choline-based PET/CT scans)
• Pathologically based node-positive prostate cancer (based on lymph node biopsies and/or peri-surgical lymph node findings)

Once again, the quality of the evidence related to how to treat these subsets of patients (taking account of other factors such as the patients’ PSA levels, their Gleason scores, etc.) is relatively imprecise. We need better data on the various subsets of these patients to see if we can gain greater confidence as to the quality of the data being used to make decisions about which patients to treat how. As well-informed readers will be aware, men with clinically evident or pathologically evident positive lymph nodes can be treted using surgery alone, radiation therapy alone, radiation therapy + ADT, surgery + immediate adjuvant radiation therapy, and even surgery + immediate adjuvant radiation therapy + ADT.

A extensive set of presentations and discussion addressed currently available data supporting the various treatment options and also what trials could or should be done in the near future to address the benefits and the risks of each type of therapy in the various subsets of patients

PSA recurrence after radical local therapy and oligometastatic prostate cancer

The day’s third session dealt exclusively with the potential ways that are now available to treat oligometastatic prostate cancer … and began with speakers noting that there is no well characterized definition of what actually constitutes “oligometastatic” prostate cancer. Indeed, by the end of the session there had been a number of new definitions proposed for specific subsets of “oligometastatic” prostate cancer that depended upon

• Whether the patient was still responding to androgen deprivation therapy (ADT)
• Whether the patients was actually castration resistant (i.e., had progressive disease after first-line ADT)
• Had true, classical, metastatic disease (based on data from a bone scan or a CT scan), and if so, how many such lesions
• Had metastases only visible of Axumin-based, or other forms of PET/CT scan (e.g., gallium-68 PSMA-based or [¹¹C]choline-based, etc.)

By the end of the session, once again, it had become very clear that we do not always know how to

• Accurately classify patients into specific subsets of “types” of oligometastatic disease
• Treat those patients in the most effective, safe, and cost-efficient manner that is correlated to the precise subtype of their disease

On the other hand, at least for the patients who have oligometastatic, castration-resistant prostate cancer that is only visible on newer forms of PET/CT scans (i.e., they have non-metastatic, castration-resistant prostate cancer or nmCRPC), we do know that those patients are likely to respond well to some of the newer forms of androgen receptor therapies (enzalutamide/Xtandi, darolutamide/Nubeqa, and apalutamide/Erleada).

We also know that there is strong evidence from Phase II trials that stereotactic body radiation therapy (SBRT) can be used effectively and safely to target evident, classically visible, oligometastatic lesions in certain subsets of patients. Expert speakers made the point that while it was not unreasonable to use SBRT in this way for carefully selected patients with specific types of lesion, we should not be expecting this form of therapy to be recommended (as yet) in treatment guidelines, because it has not been proven in a highly defined set of patients in a well-designed, randomized, Phase III clinical trial.

What is more, we really have no idea what to do with patients who have castration-resistant prostate cancer and one or two metastases that are evident on classical imaging scans but multiple lesions that are evident on the newer PET/CT scans. Should these patient be getting treatment with one of the newer forms of androgen receptor and directed SBRT? Maybe. Of course this will require further clinical trials as well.

Regional care (demographic and environmental factors)

This session dealt with issues of ethnicity and sociobiological factors in different regions of the world and how they impact the diagnosis and management of advanced prostate cancer over time. It would be very difficult to summarize all of the factors addressed in this particular session because so much of the data presented was dependent on the specific country or region of the world to which the speakers referred or the subset of patients being referred to.

At this time, what is clear is that there are all sorts of regional, ethnic, and other reasons that may be are are affecting how individual patients with advanced forms of prostate cancer are getting treated (or should be getting treated) in different counties around the world. What is a lot less clear is whether what is actually happening in different countries is either as well defined or as well conducted as we might like it to be.

Having said that:

• Some excellent data were presented as to why many Asian (e.g., Chinese) patients should be treated with docetaxel chemotherapy at significantly lower doses than those being given to US-based patients, primarily because the average body mass of Asian patients is a great deal lower than that of US patients, so use of a lower dose of docetaxel lowers risk for toxic effects of docetaxel in Asian patients from that seen when they are administered “standard” doses of docetaxel.
• The use of pre-emptive, primary G-CSF along with docetaxel chemotherapy has significantly lowered risk for specific hematologic side effects in Japanese patients.
• A series of recommendations for the treatment of prostate cancer were presented for areas of the world with low levels of medical resource, based on a global consensus meeting held in December 2018.
• The issue of appropriate treatment of the elderly (i.e., geriatric patients) with prostate cancer was specifically discussed.

The core message that yous sitemaster suggests that readers should take away from this first day’s discussions at the APCCC is that while we have made enormous progress in understanding how to better treat progressive forms of prostate cancer over the past 30 years, we have an increasingly long way to go in determining “the best” ways to treat definable subsets of patients because of:

• All the new diagnostic and prognostic tools that are now available to clinicians for use in better characterizing specific subsets of prostate cancer
• The limited amount of solid knowledge (and the limited numbers of experts) available to accurately interpret some of these data and then use these data appropriately in the actual treatment of individual patients
• The real-world issues related to access to high-quality care for something like 75 percent or more of the world’s prostate cancer patients

Here on the InfoLink site, we largely — on a routine basis — are focused on forms of diagnosis, prognosis, and management that are available to people living in the “Western” world of men who have relatively high-quality healthcare insurance (i. through commercial or state-facilitated healthcare systems of differing types). The reality of prostate cancer healthcare in most of the world, however (Africa, South and Central America, much of Asia, and even a good deal of the Middle East) is that the types of health service that we take for granted (LHRH agonists; IMRT; drugs like enzalutamide and apalutamide) are either unavailable or unaffordable for all except the very rich.

Thus, in the western world we are trying to put high quality protocols in place so that we can execute “precision medicine” in the management of prostate cancer, but for the vast majority of men with advanced prostate cancer in a county like Brazil or Equador or Nepal, the normal first-line treatment for a diagnosis of metastatic prostate cancer is still a bilateral orchiectomy — fbecause it is simple, low in cost, and can be carried out easily by any competent surgeon. Your sitemaster has no idea how many men in America each year receive a bilateral orchiectomy as first-line treatment for metastatic prostate cancer, but in some poorer parts of even one of the richest countries in the world — e.g. Appalachia — it may still be more common than you think.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: APCCC, genetics, genomics, node-positive, oligometastatic, recurrent |