It's Not About the Organ

Raoul S. Concepcion, MD

Editor-in-Chief of

Urologists in Cancer Care

Director of Clinical Research Urologic Surgeon Urology Associates, PC Nashville, TN

I am sure that those of you who attended the AUA meeting in Orlando were struck by the number of presentations on the use of biomarkers and their role in better risk stratification and management of the urologic oncology patient.

Obviously, many of these investigations have been focused within the world of prostate cancer. Questions in this disease state abound. Is there a better test than PSA to determine who needs an initial biopsy? Given the severe limitations of transrectal ultrasound and sextant biopsy, what assay(s) might help us decide who is the prime patient for active surveillance, or who may need a repeat biopsy if the first was negative? Lastly and most importantly, what noninvasive methodology or lab testing can be utilized routinely to monitor our current therapies and patient response?

We are coming to an understanding that cancers have some commonalities across the board. For the most part, our immune system does a yeoman’s job of monitoring our microenvironment. It efficiently weeds out aberrancies and protects us from foreign invaders. But like any security system, there will be the occasional breach, which could result in a catastrophic event. As it relates to the human body, this would mean the creation of a rogue state with potentially unregulated malignant cell growth.

Fortunately for our patients, we continue to move in a positive direction as we gain a better understanding of this incredibly dynamic and complex process. Gone are the days of routine “bleeding” to rid our bodies of evil humors. Surgery and radiation continue to be mainstays of therapy for select tumors, but they, too, are on the decline as our therapies become more molecularly based. And, as we all know, traditional cytotoxic chemotherapy is being re-evaluated.

New therapies are being developed rapidly, and it is imperative that we adjust our mindset to look at cancer development and progression in a mechanistically different fashion.

Traditional cancer-center models and therapies revolve around the organ of origin. We view tumor types based on the organ in which they are discovered. Our clinical trials revolve around the same concept: Let’s get approval for this therapy in this particular organ in a patient with this particular cell type and clinical characteristics. But in reality, neither a cancer nor its treatment is about the organ of origin. We are now of the belief that cancers are driven by common pathways that may happen to start in the prostate, breast or lung. The tumors can unfortunately mutate, and resistance to therapy is due to a new or distinct pathway that allows escape. These mutations may in fact be due to selective pressure of the treatment being used. Thus, therapies need to be developed and tested to target these pathways and epigenetic factors.

We know that immunotherapy is here to stay. Targeting the patient’s own immune system makes complete sense, given its role in surveillance, whether that be active or passive. Therapeutic vaccines, checkpoint inhibitors, advanced monoclonal antibodies: All will hopefully have a role in the management of our patients as we turn more and more toward precision medicine and the development of orphan drugs that target specific biomolecular targets. The field of “omics”—genomics, proteomics, and metabolomics— will hopefully become part of our nomenclature. Ideally, this will be the new paradigm as we move forward.