Raoul S. Concepcion, MD
Urologists in Cancer Care
Director of Clinical Research
Urology Associates, PC
Two years ago, I diagnosed a longtime friend with Gleason 3 + 3 prostate cancer, two cores positive, less than 10% of each core involved, and a prostate volume of 110 grams (with no voiding symptoms).
After a long discussion regarding treatment options, I recommended active surveillance. My friend, an attorney and very well read across many topics, was more familiar with the then-common terminology used in the lay vernacular: “watchful waiting.” He looked directly at me and asked: “What am I waiting for…to die, or for this thing to spread?” He then proceeded to use a comparison that has opened my eyes to what personalized medicine is all about. He likened his situation to being a soldier sent into battle, knowing that his chances of survival were grim.
If you are one of the unfortunate to be thrust into that position, he pointed out, your interest at that moment is not your fellow soldiers. All you really care about, for the most part, is “What happens to me?”
When we have that difficult discussion with our patients about how to best manage their particular cancer, we quote percentages of survival, recurrence-free disease, and mortality based on large numbers of patients with similar clinical characteristics and histopathology. We relate our own personal and institutional data, as well. What we do not take into account, at least for now, is the patient and his or her unique tumor.
Every patient’s immune status is different. Every tumor and the way its cells respond to the local environment is different, based on the genetic profile, and many other factors, of the host, our patient. The grade and stage may be the same from patient to patient, but the pathways for escape and the tumor’s ability to mutate may be different.
If you attended the AUA’s Annual Meeting this year, you know that one of the hot topics for discussion and presentation, besides PSA guidelines, revolved around biomarkers in prostate cancer. Is there adjunct testing beyond Gleason, stage, and PSA that can help us answer the question posed by our patients? Can we start to look at the signature of these tumors to better stratify who needs treatment and who we can observe? Whether it is genetic sequencing, epigenetic mutations, or proteomics (and we are far from the definitive test), that is the direction in which all of us who manage patients with malignancies should be going.
This holds true not only when it comes to predicting progression and aggression, but also in the advanced stage, where we need to be pairing therapeutics based on the genetic/protein marker to see the response from our many oncolytics that are now available. This is germane to all cell types. Imagine if we could better predict which patients’ non-muscle-invasive urothelial cancer would never progress to muscle-invasive disease. Yes, we would do less cystoscopy, but we would also bend the proverbial cost curve and better position ourselves to be the ones who manage urothelial cancer. This becomes important in the changing healthcare environment.
As most of us are aware, there are many therapies currently available for the management of the patient with castration-resistant prostate cancer (CRPC). All have different mechanisms of action, and all confer survival benefit as monotherapies. The burning questions are: What is the appropriate sequencing, and which combinations might be superior?
Should these determinations not be based on the patient’s tumor? A colleague and friend once told me that we do research incorrectly. We study drugs, not patients. If we enroll a patient in a clinical trial and there is progression, the patient is dropped. While that makes sense within the design of a trial, shouldn’t our broader goal for that patient be to change therapies based on what his tumor is expressing?
I know that many of you will say I am being too idealistic, and that we are years, maybe decades, away from having that ability. But we need to start somewhere and adjust our thinking about how malignancies develop and progress beyond definitive therapy. Perhaps we should move away from directing therapy based on the primary site of malignancy—lung, colon, prostate, pancreas, etc—and focus our efforts on inherent pathways common to the tumors, irrespective of the organ.
Moving forward, I hope to offer you more articles elucidating these concepts. It behooves all of us to understand what is driving these tumors at a cellular level, and how we can better utilize that information to manage our patients. Perhaps then we can more definitively answer the top question on our patients’ minds: “What happens to me?”