I recently had reason to survey the progress made in renal cell cancer (RCC) over the last 70 or more years. In 1950, a patient who presented with metastatic RCC had a 0%-5% overall response rate (ORR) to the therapies of the time, with an anticipated overall survival (OS) of approximately 10 months. By 2005, those numbers had changed marginally, signifying no progress in more than 60 years despite honest efforts.
Although the introduction of more effective therapies stagnated, scientists toiled tirelessly to understand the genetics and subsequent pathways of this highly angiogenic and immunogenic cancer, so that after the turn of the millennium, novel therapies were ready for clinical testing. Since 2005, dozens of treatments have been tested and approved after hundreds of trials involving thousands of patients.
The results are nothing less than staggering. In the span of 14 years and after a sustained period of what I call “progresslessness,” there has been a nearly 10-fold increase in ORR and 5-fold improvement in median OS survival. These results over such a short period of time are on par with breakthrough discoveries in medical sciences that our physician predecessors lived through, including development of vaccines and antibiotics.
It may be easy to dismiss the progress made in treatment when facing a patient whose disease marches on despite these therapies, but one should keep in mind the new therapies that have come along to fight cancer pioneered by basic scientists in the kidney cancer space, including monoclonal antibodies against VEGF; tyrosine kinase inhibitors; mTOR inhibitors; checkpoint inhibitors; and oral inhibitors of hypoxia inducible factors. Basic science has converted the most recalcitrant of all advanced urologic tumors to among the most treatable, and in so doing is causing a frame shift in the management of many solid malignancies. Today, these agents meaningfully slow and occasionally cure disseminated disease, bending previously dismal survival curves on our way to converting cancer to a chronic disease state.
It has been said that science is an endurance sport as there are decades where nothing happens followed by moments where decades happen. We should be no less astonished by the pace of progress than the physicians 80 years ago administering penicillin for the first time to bacteremic patients. The survival curves are bending downward at long last and physicians have a front row seat.