Although there has been much discussion about improved survival in cancer, most of the progress has reflected screening, earlier diagnosis, improved staging, and better supportive care. With regard to the millions of patients diagnosed at first presentation with metastatic disease (Stage 4), progress has been exceedingly slow.
A recent article in the Journal of the National Cancer Institute (Luyendijk, M. JNCI, June 2023) described just how slow progress has been. Dutch investigators compared outcomes between 1989 and 2018 for one and five-year survival in over 2 million patients with a focus on metastatic disease. First, it must be recognized that some cancers have a propensity for late diagnosis. Indeed, half of all patients with pancreatic cancer present with metastatic disease.
Secondly, there have been real gains in a small number of diseases like gastrointestinal stromal tumors (GIST), neuroendocrine tumors (NE), and melanoma. This is reflective of new therapies introduced in the last 2 decades that have proven effective for this minority of patients.
However, the newer targeted agents for the most part have provided small survival gains, with 22% of these medicines offering no survival benefit whatsoever over standard of care, despite enormous costs and significant toxicity.
More importantly, even for targeted agents that prove effective, improvement in survival is a meager 3 months on average.
The conclusion of this study is that the one and five-year survival rates of some cancers have changed very little in the last 30 years.
What cancer patients should be asking themselves is, “How can this be improved?”
First, we must recognize the limitations of the “much-hyped” genomic analyses for the prediction of response. Only a minority of cancer patients have actionable mutations (DNA targets), and even these fortunate few are virtually never cured.
Second, we must recognize that each patient is unique. Forcing patients into standardized treatment protocols undermines the need for patient-centric individualized care.
Third, we must incorporate more systematic approaches to cancer research that move beyond genomics to apply the more biologically relevant study of metabolomics.
Indeed, metabolism may be the final frontier for cancer research, as we move from DNA- directed therapies to metabolic inhibitors capable of depriving cancer cells of the very nutrients and energy sources that keep them alive.
Sadly, this JNCI paper is not surprising. It should be obvious to many that progress has been painfully slow, and more importantly that different approaches must be undertaken.
Cancer biology is complex. The scientific reductionists who control much of modern cancer research have attempted to simplify cancer to nothing more than a few alterations in genes, and they have been manifestly unsuccessful.
Nonetheless, there is reason to be optimistic. Human tumor studies like EVA/PCD, capable of examining cellular response to drugs and targeted agents, with a growing focus on metabolic inhibitors, offer hope for the millions of patients every year who present with metastatic disease.