COMMENTARY

Our Failures Demand a New Approach to Cancer

Azra Raza, MD

Disclosures

December 05, 2019

A few weeks before his death, 23-year-old Andrew—my daughter's best friend—was approached about a DNR (do not resuscitate) order. He was suffering from end-stage brain cancer, but he refused outright to even consider signing.

Source: Chad Hunt

That evening, however, when his father came to spend the night with him, Andrew asked for the form and quietly signed it. "I did not want to do it while my mother and sister were in the room," he said.

Andrew was diagnosed 16 months prior with a particularly aggressive, unresectable glioblastoma multiforme. From the moment of diagnosis, every oncologist who treated him knew there was no hope for any long-term survival. Yet, he received round upon round of aggressive, toxic therapies until he died. Why? Because if he did not receive at least palliative therapy, the rapidly advancing cancer would be even more painful. His choices boiled down to dying from the disease or dying from the treatment.

The outcome for those with advanced disease is marginally improved or no better than it was half a century ago.

Andrew forced me to accept that we have failed our patients with advanced cancer, both as oncologists and as a society. The War on Cancer, declared in 1971, infused the field of oncology with huge sums of money, attracting brilliant minds to research as well as savvy business executives who spotted a chance to benefit monetarily. Yet today, almost 50 years later, only a select few patients with common types of advanced cancer are cured while more than a third are financially ruined 2 years after diagnosis.

Here is the problem: With few exceptions, and despite billions of dollars in research and millions of publications, the same old slash, poison, burn (surgery, chemotherapy, radiation) strategies to treat cancer prevail. We've sought comfort in the way things have always been done; if everyone else is doing it, it must be right. As a result, the outcome for those with advanced disease is marginally improved or no better than it was half a century ago. Do we really expect that pouring ever-increasing amounts of money into the current treatment paradigm will provide a real solution?

Instead, let us bring the patient back into the picture, front and center, and ask some fundamental ethical questions: Why are we subjecting a majority of patients to unbearable physical discomfort and financial ruin so that a small subset may experience a borderline improvement in survival measured in months and not years? Why are our regulatory agencies, who have been charged with protecting patients, approving therapies with tremendous risks without attempting to define who the likely responders are? And why are we even developing treatments that are so horrendous that entire industries are emerging just to deal with the toxicities, where we must constantly ask ourselves whether the cancer or the treatment will ultimately kill the patient?

Our patients deserve better. For those with cancer now, we should, first and foremost, stop adding to their pain and suffering; at the same time, we must take infinite care not to break their spirit.

And for our future patients, let's reverse the treatment model. Current treatments attempt to kill the last cancer cell. Instead, we should go after the first cancer cell, diagnosing not minimal residual disease but minimal initial disease, and prevent the very first cancer cells' expansion into an end-stage monstrosity that is almost impossibly difficult to contain. While there has been no noticeable change in survival for advanced cancer, there has been a 26% drop in mortality from all cancers over the past 50 years. Most of this is due to a decline in smoking and the success of periodic screening measures like mammography, colonoscopy, Pap smears, and prostate-specific antigen testing.

In order to uncover and attack the first cancer cells, the next generation of monitoring technologies will use sophisticated biomarkers and imaging devices capable of scanning and identifying disease-related perturbations at a molecular level before the clinical appearance of symptoms. The human body can, and should be, monitored continuously so that preventive measures can be instituted in a timely fashion. In such a scenario, individuals at risk for certain cancers due to germline polymorphisms or a history of carcinogen exposure can be selected for highly focused screening.

Some of the best solutions may emerge by questioning what we have been taking for granted.

Every solution breeds a new set of problems. There will always be the potential for overdiagnosis and overtreatment in cancer. This is a legitimate concern but one that can be mitigated with careful planning. For example, there is no need to rely solely on any single test as the ultimate proof of trouble. Rather, if a scanning method reveals a hot area, it should be followed closely and cautiously for signs of growth. Simultaneously, supplemental biomarkers associated with cancers in a particular organ should be sought in the blood, saliva, urine, stool, or breath. Only when all signs point to a malignant presence with a lethal potential should attempts be made to rid the body of the offending cells. Some of the same therapies that may not benefit patients with advanced cancer could be more helpful in early-stage disease. Chronic myeloid leukemia is a case in point: Imatinib can be curative during the chronic phase but useless as a single agent during blast crisis.

Ultimately, as cancers are diagnosed earlier, preventive measures will be dramatically less severe than treatment measures. They will also help dissipate much of the anticipatory anxiety that patients feel when given the news that they are at high risk for cancer.

Some of the best solutions may emerge by questioning what we have been taking for granted. Examining dogma and received wisdom through the prism of human anguish like Andrew's will create a rival paradigm in cancer research, one focused on protecting all patients.

When I look back at Andrew's experience with our current treatment approaches, I'm struck that he almost never gave in to despair in the presence of his family and friends. He shielded them by showing good cheer even as he suffered unbearable pain. Nations should be dedicating monuments to the nobility of his strength. Many of us have treated patients like Andrew. How many more will it take for us to finally demand a different approach to getting this disease under control?

Azra Raza, MD, is the Chan Soon-Shiong Professor of Medicine and director of the Myelodysplastic Syndrome Center at Columbia University in New York, NY. She is the author of The First Cell: And the Human Costs of Pursuing Cancer to the Last.

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