If we ask someone what the goal of cancer medicine is, the answer is almost automatic: cure itmake it disappear or win the war against this devastating disease. However, in molecular biology laboratories and advanced oncology consultations, the verb is changing, since we no longer speak of “eradicating” at all costs, but to contain. An idea that may be quite shocking, but which is proposed as the future of medicine.
The idea. Douglas Hanahan, one of the most influential figures in modern biology and one of the great responsible of the hallmarks of cancerwhich are the hallmarks that define a tumor, has put this idea on the table. In this case, it points to a concept that clashes with our intuition, but fits with scientific data: cancer without disease.
The idea is provocative, since it suggests that histologically malignant tumors are possible living off of us without killing us or affecting our quality of life. The objective is no longer the total elimination of the enemy and becomes something more pragmatic: keeping it under biological and clinical control so that the patient dies with the cancer, but not from the cancer.
There is no cure. In a recent interview and in your updates of the Hallmarks of Cancer 2022, Hanahan insists that the complexity of cancer makes a universal cure unlikely. Instead, it proposes to understand what specific capacities sustain the tumor, such as evasion of the immune system, inflammation, replicative immortality… to selectively block them.
In this way, it is not about destroying the entire tissue, but about converting a lethal process into an indolent one. This is what Hanahan calls “adaptive resistance”, since we assume that the tumor will try to look for new escape routes, and we will change the therapeutic strategy to block them, maintaining the tumor ecosystem within safety margins.
It already happens. All of this is not a futuristic theory, but rather it is already happening on two very different fronts: the tumors that we decide not to touch and the aggressive tumors that we have learned to stop.
Not trying is sometimes the best. The most literal example of “cancer without disease” is found in the prostate and thyroid. Here, diagnostic technology has advanced so much that we detect tumors that, biologically, would never have caused problems.
In the case of prostate canceralmost half of low-risk tumors now enter active surveillance protocols. In this way, instead of operating or radiating (with the risk of impotence and incontinence that entails), doctors begin to monitor the mass. And the data, after 20 years of follow-up in large groups of people, are quite clear: cancer-specific mortality in these well-selected groups is less than 1%.
In the clinic. With all this, the idea is that it is better to live with a controlled cancer than to pay the physical price of curing it, although logically, if it goes too far out of containment, the most correct thing is to try to eradicate it with the tools we have.
In the case of papillary thyroid cancer We also have this same situation, since overdiagnosis has led to stopping aggressive surgery in favor of observing tumors that the body keeps at bay on its own.
The new chronicity. Where the paradigm changes most dramatically is in advanced or metastatic cancer. Twenty years ago, a diagnosis of stage IV lung cancer or metastatic melanoma was almost invariably a short-term terminal sentence. Today, thanks to immunotherapy and targeted therapies, a new category of patient has been born: the “treatable but not curable.”
With this strategy there are already different organizations, like the British NCRIwhich describe growing cohorts of patients living for years with the disease. In this case they have metastases, but they live a normal life with their jobs and trips while receiving chronic or intermittent treatments to contain the disease. But without staying on the road.
Changing the rules. This new paradigm within oncology has forced changing the rules of the game in clinical trialssince the aim is no longer just for the tumor to disappear, but for prolonged stabilization.
With regard to toxicity, the logic of “maximum tolerated dose” in chemotherapy (give medication until the patient can tolerate it) does not work if you are going to treat the patient for five years, since their quality of life with very aggressive chemotherapy will decrease each time. Right now, quality of life and low toxicity are prioritized with ‘milder’ medications to allow long-term treatment without major side effects.
This is why cancer is beginning to resemble, in its management, diabetes or HIV: a chronic condition that requires lifelong medication, but that does not necessarily dictate the date of your death.
Psychological problems. Logically, this model of ‘chronic cancer’ has its shadows. Medical literature warns, for example, that living with “dormant” or controlled cancer places an enormous mental burden on patients. Studies on active surveillance show that, for some patients, the anxiety of having a “ticking time bomb” inside worsens their quality of life more than the surgery itself. And each review consultation can mean a world to know if it has gone more or less.
And more problems. In addition to this, you must know that not all of these diseases can become chronic, such as glioblastoma or pancreatic cancer, which continue to have an aggressive biology that, today, escapes this lazy control.
But also, turning cancer into chronic is great news for the patient, but a titanic challenge for public health, since it implies treating more people, for more years, with very high-cost biological drugs.
The summary. Hanahan’s “cancer without disease” is not giving up. It is accepting that, if we cannot eliminate the enemy, victory lies in keeping it at bay long enough for life to continue its course and even allow science to continue advancing. As mortality statistics suggest: more and more people are dying with cancer, but fewer people of cancer. And in that nuance lies an entire medical revolution.
Images | National Cancer Institute Angiola Harry
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