Advancements in targeted therapy and immunotherapy have led to a rapidly increasing number of patients with metastatic cancer becoming patients with chronic cancer.
Evan Wu, MD
Immuno-oncology, the redirection of one's immune system to fight disease, is the single most important recent discovery, both in oncology and all of medicine. Immuno-oncology is the redirection of one’s own immune system to fight off cancer. It has produced remarkable clinical outcomes in patients who were previously given a death sentence.
Although only in early stages of development, there are a host of adverse events and failures associated with immuno-oncology. However, investigators are expanding on the work done by this year’s winners of the Nobel Prize in Physiology or Medicine, James P. Allison, PhD, and Tasuku Honjo, MD, PhD, at an extraordinarily rapid pace. We are discovering new targets for immunotherapy and learning how to use these agents in combination with other anticancer therapies.
As a medical oncologist in training, the most frequent question I get asked by peers outside of the medical field is when we will “cure” cancer. I am always astounded and disturbed by the simplicity of the question. Some cancers, such as testicular cancer and certain hematologic malignancies, are effectively curable already. But the biology of cancer development is so complex and individualized to each patient’s tumor that it is incredibly difficult to categorize even tumors of the same organ and histological subtype.
However, an incensed rant is not what the average layperson is looking to hear from an oncologist, so this is my not-so-simple answer to the “curing cancer” question.
First, most early stage cancers are curable simply by removing them. One may argue that there will be more early stage curable cancers and less advanced cancers as screening mechanisms improve. But it is nearly impossible to imagine a situation where we could successfully prevent all advanced cancers from ever developing simply through early detection.
Colon cancer screening will still require regular colonoscopies, although there is always the possibility of novel biomarkers. Breast cancer will still depend on mammography and/or MRI. Hematologic malignancies will be caught on routine blood tests, and screening CT scans will never be a financially realistic option to catch all lung and upper gastrointestinal cancers.
Therefore, the primary focus of the question of curing cancer centers on advancements in the treatment of metastatic cancer. During training, oncologists are taught to call all metastatic cancers incurable and to emphasize the point that all treatment for metastatic disease is palliative. Recent developments in targeted therapies and immunotherapy have challenged this treatment paradigm.
In the very best, albeit exceedingly rare, cases, tumors dissolve away with immunotherapy, leaving no radiographic or clinical evidence of metastatic cancer. More often, the targeted agents and immunotherapy treatments lead to a prolonged state of stable disease. How cancer frequently detail women with metastatic disease on targeted therapy living otherwise healthy and normal lives for 10 years or more. Many patients with metastatic melanoma and lung cancer previously treated with immunotherapy are also nearing or surpassing a decade of survival living with metastatic cancer. Although oncologists will never call these patients “cured,” they certainly do not fit the traditional mold or trajectory of patients with metastatic cancer.
As more and more of these patients accumulate through the improved therapies, this country will continue to collect a substantial population of patients with “chronic cancer.” These patients will represent an overwhelming majority of our cancer clinic population and represent a new normal for the meaning of and our treatment approach to metastatic cancer. Patients will always be horrified and distraught from the diagnosis of metastatic cancer, but rather than immediately planning their will and traveling the world before they die, they can be assured that the new normal could easily mean 10-plus years of quality living with a chronic disease.
An appropriate analogy is to compare cancer to the evolution of HIV. In the early stages of HIV, the diagnosis was a death sentence. As treatments dramatically improved, however, and we learned about the complex biology of HIV, we have still been unsuccessful in curing HIV. But we have managed to turn HIV into a chronic disease. The virus remains dormant in one’s cells just as cancer remains controlled in one’s organs or lymph nodes. Stopping antiretroviral therapy may result in disease relapse much as how stopping targeted therapies will result in disease progression.
The often-asked simple question of “curing” cancer has 1 simple answer: NO! We will not cure cancer; we will never cure cancer. We will not figure out every mechanism of resistance and every mutation that causes every type of cancer. And yet, advancements in targeted therapy and immunotherapy have led to a rapidly increasing number of patients with metastatic cancer becoming patients with chronic cancer. We will continue to see more and more metastatic cancers become chronic conditions, and the oncology world will be full of patients living with the chronic disease known as metastatic terminal cancer.