Minding the Gaps in Prostate Cancer Treatment – Philippine Endourological Society

Treating cancer is hard. Its even hard when you have years of experience and are considered an expert.

Communication with patients is always a challenge, as is gathering all the information you need to make an informed decision. Then there’s the energy and time that are required to keep up with the clinical literature in your space, and the scientific/basic literature of it if you are so inclined.

I am not a highly disciplined regular reader of a stack of journals. I am impressed by those who are. I am a talker, and an extrovert, and I also like to explain things and have them explained to me. Perhaps that is why I chose a niche within my career that allows me the great opportunity to teach, lecture and explain things a lot. I like doing that. Its how I learn.

One of my greatest challenges is that I like to think out loud. This has served me well at times and not so much at others. Sometimes the thoughts that come through ‘out loud thinking’ are incomplete, improperly informed, or just plain dumb.

But let’s dive a little deeper on where thinking out loud can be highly useful. Consider the discovery of gaps in our knowledge.

I’m not sure why, but I feel like ‘evidence based medicine’ isn’t quite the buzzword it was years ago – for example during the time of my medical school and residency training -the mid 1990s. During that era I had professors who attempted to be able to cite evidence for every medical decision they made – and would remain agnostic on areas where there wasn’t level 1 evidence or something close to it. It seemed slightly paralyzing at times.

We can’t really function that way. There are gaps in what we can do when we treat prostate cancer – big ones. And level 1 evidence is costly to get, labor intensive and not always collected with clinical decision making in mind. As we focus on castration-resistant prostate cancer (CRPC), consider these two ‘conundra’ in CRPC:

1. Non metastatic CRPC: Treat? Wait? Which drug? We now have a lot of data in this setting, but I still think there is a gap concerning when and if, we should start one of the AEDA agents ( Apalutamide, Enzalutamide, Darolutamide or Abiraterone). Interestingly, I have also had the following experience in this setting: When trying to prescribe apalutamide to a nonmetastatic CRPC patient, the pharmacy recommended that I Rx Abiraterone instead, which is on formulary for this condition, and far less expensive in this setting, but not supported by level 1 evidence. I thought that was funny, and would have figured that a formulary committee might go the opposite direction and NOT recommend it. In fact, I know the data on Abiraterone in nonmetastatic CRPC pretty well – because I led and published the IMAAGEN study, that demonstrated results that compare very favorably with Apalutamide, Darolutamide and Enzalutamide – but IMAAGEN was not a placebo controlled study. So is it level 1? Its not, that’s a gap, but I think extrapolation may be ok in this setting. Apparently at least one formulary committee agrees.

2: CRPC after up to date metastatic hormone sensitive prostate cancer (mHSPC) treatment. This is a big one for me and I think for many of our colleagues. It is great to tell a patient that we are making great progress on the initial management of high or low volume mHSPC through the addition of docetaxel, abiraterone, enzalutamide or other therapies. The challenge is that the moment a patient who has received this approach develops CRPC we fall into a gap. Imagine a patient now with CRPC who has already ‘seen’ ADT plus enzalutamide. They may have a low volume of disease because they responded well to that combination, and are likely symptomatic. Should that patient get docetaxel? They are likely not symptomatic enough for radium, and there is not likely to be much gain from replacing then enzalutamide with abiraterone, apalutamide or darolutamide., So what do we do? I personally have been all over the map in this setting. Apart from sequencing the tumor and hoping for a rare but exciting finding of an MSI High or BRCA2 mutated tumor, when I can help generate data and likely help the patient, we are in a data free zone.

I bring up these cases not because I have the answers, but because I am comfortable with the ambiguity in these situations. Also, there is a solution, and this is the week we explore those solutions and offer them for the world.

The best way to mind the gap is to find consensus. That’s what we do around the kitchen table, in diplomacy, the courts (some of them) and in politics.

A few dozen clinicians from all over the world will gather in Switzerland this week to answer questions like those posed above and more. We will vote, and the results will be published. Any clinician anywhere can lean on those results and take solace knowing that we all recognize that data do not exist for all corners of prostate cancer management, but perhaps if dozens of experts agree on a path of treatment in these gaps, that one can recommend it and counsel patients with confidence.

But do we need to be “experts”? Unsurprisingly, I have found that some of the clinicians who treat a relatively low volume of prostate cancer patients can have some of the most thoughtful strategies for treating them – often pulling from their experience treating other malignancies like breast, lung or colorectal cancer, on a daily basis – something I don’t do. And they are often the ones who do regularly pore through the stacks of journals that I don’t. They are indeed experts, but framed in a slightly different perspective.

That is why we have worked to offer a sampling of the Advanced Prostate Cancer Consensus Conference (APCCC 2019) expert consensus questions to all clinicians who treat prostate cancer globally. Those thoughtful, busy, and diversified clinicians have something to teach us. If you are among them, click here to take the survey!

A certain aura surrounds the fact that we gather in Switzerland to build consensus, of all places. These are tumultuous times in the world, even though the world of oncology and cancer care for the most part stays above the fray, I still feel that gathering to form consensus in the peaceful and famously neutral country has some sort of symbolic significance. I look forward to vigorous discussion, some debate, some disagreement and even a celebration of our collective presence in the gaps.

Written by: Charles Ryan, MD, Professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, United States