Neal J. Meropol, MD, FASCO
Recently, I had the honor of coauthoring a chapter with Eric P. Winer, MD, President-Elect of ASCO, on the evolution of clinical cancer care since the enactment of the National Care Act of 1971 for the book A New Deal for Cancer: Lessons From a 50-Year War, by Abbe R. Gluck and Charles S. Fuchs, MD, MPH (Public Affairs, 2021). Writing the chapter gave me the opportunity to reflect on how policy and research investment since the implementation of the National Cancer Act have altered the oncology landscape, and what is likely to come next if we take advantage of the stage that is now set. The National
Cancer Act established today’s National Cancer Institute (NCI), with an NCI director endowed with significant authority, with an annual budget submission directly to the President and Congress, and empowerment to appoint advisory committees, award research grants, collaborate with the public and private sectors in the United States and internationally, and an expanded budget to create new cancer centers and other cancer control programs. In addition, the law established the National Cancer Advisory Board and President’s Cancer Panel, solidifying close executive branch involvement in national cancer programs.
The second decade or so after the law went into effect, which coincided with the early days of my career, including my fellowship training in the late 1980s and early 1990s, was still characterized by talk of finding “a cure for cancer.” But harkening back to those unrealistic expectations can obscure the truly transformational changes that have occurred in cancer care since the bill was passed; they were both important incremental advances as well as more groundbreaking developments, building upon fundamental discoveries and new technologies.
It can be easy to miss that cancer mortality in the United States has decreased by 32% since 1991.1 Unfortunately, not all members of society, including racial and ethnic minority populations, have benefited equally from improvements in cancer outcomes.
Looking Back on the Early Days
When I was in medical school in the mid-1980s, I learned of the Nobel Prize–winning work about a new method to generate monoclonal antibodies, the characterization of a growth factor that accelerated the opening of the eyes of newborn mice (epidermal growth factor), and the early use of a new imaging modality based on magnetic resonance. At that time, screening sigmoidoscopy was still often performed with a rigid scope. Bone marrow transplantation was a dangerous new procedure that required stays in inpatient isolation rooms of more than a month. Cancer surgery was commonly disfiguring. And radiation and chemotherapy were blunt instruments, with limited examples of curative potential.
As a fellow, I witnessed a transformation in supportive care, with the introduction of hematopoietic growth factors and serotonin antagonists, and the initial recommendations for adjuvant therapy in patients with node-negative breast cancer and those with high-risk colon and rectal cancers. These examples underscore that for those of us who cared for patients in the latter 20th century, it is difficult not to recognize the advances we have witnessed.
Assessing Advances in Cancer Care
What has changed? When I think about how far we have come, I see the biggest contrasts with those early days in oncology as falling into three broad buckets:
- What it means to receive a cancer diagnosis
- Innovative applications of science and technology in routine care
- Where and how patients with cancer receive their treatment.
When the National Cancer Act was passed, cancers were commonly diagnosed at a late stage, and prognoses were poor. Treatment options were narrow and associated with high morbidity. Patients often considered their diagnosis to be akin to a death sentence, and it wasn’t uncommon for them to be secretive about their diagnosis and isolated from friends and family. Today, cancer screening, early detection, and more effective treatments have all contributed to improved survival rates and a growing cancer survivor population of nearly 17 million in the United States.2
At the same time, the cancer advocacy community has grown and become more sophisticated, which has led to increased public awareness, research funding, and support networks. These factors have fundamentally altered the meaning and the aftermath of a cancer diagnosis.
In addition, investments in cancer research and technologic developments have dramatically improved the ability to successfully prevent, diagnose, and treat patients with cancer. Vaccines, genetic-risk evaluation, and risk-modification strategies are preventing cancer development, with screening methods for common cancers leading to early detection and risk reduction. Noninvasive diagnostic approaches using radiologic techniques, including positron-emission tomography and magnetic resonance imaging, and laboratory methods, such as molecular biomarkers, are now standard of care.
New technologies, biologic insights, and a greater understanding of the natural history of cancer have led us to less invasive and more targeted surgical and radiotherapeutic interventions. In terms of treatment, it is impossible to overstate the impact of sequencing the human genome for cancer care. Rapid gene sequencing, amplification, and editing, with laboratory automation, have led to the identification of new treatment targets and associated therapies. The molecular drivers of many cancers are now identified, and the widespread availability of genomic profiling permits the identification of rare gene alterations with associated systemic treatments that dramatically change the prognosis for an increasing proportion of patients. In 1971, bone marrow transplantation was a niche research endeavor. Today, cell therapies, including hematopoietic stem cells and engineered chimeric antigen receptor T cells, are routine curative approaches for numerous, previously fatal, hematologic cancers.
Finally, although the notion of immune surveillance and cancer immunotherapy existed long before 1971, it is only recently that the immune system has been leveraged at scale for cancer treatment with the success of checkpoint inhibitor therapies. With each new report of the long-term follow-up of checkpoint inhibitor studies, it is increasingly clear that some patients with advanced solid tumors can be cured with systemic immunotherapy. In 2021 alone, the U.S. Food and Drug Administration approved 17 new treatments for patients with cancer.3 For today’s oncologists, precision medicine is not an aspiration—it is a reality in everyday practice.
Back in 1971, cancer was largely treated in the inpatient setting, with surgery as the primary treatment modality. Today, cancer treatment is often conducted in the outpatient setting and may span years, while patients continue to raise their families, work, and live their lives. These factors have altered the way cancer care is delivered.
Cancer care is now a team effort that involves multiple modalities and takes place mainly in the outpatient setting. The complexity of diagnosis and treatment selection requires the involvement of many professionals beyond the primary oncologist, including nurses, advanced practitioner clinicians, clinical pharmacists, molecular pathologists, social workers, radiologists, and mental health professionals, as well as other subspecialty experts.
Multidisciplinary tumor boards are considered a quality standard, given the frequent need for multimodality treatment decision-making and coordination. Such care coordination may require patient navigators to assist with even the savviest patients.
Another factor that has achieved prominence in recent decades is the financial impact of a cancer diagnosis due to the increasing cost of cancer care and cost-sharing even among insured patients. Financial toxicity in cancer care is now a recognized consideration in treatment decision-making.
Predicting What’s Next
So, what could be possible in cancer advancements over the next 50 years? Critical investment in basic biologic research, enabled by new laboratory technologies, will provide additional foundational insights essential to the next wave of transformative advances. The steep trajectory of discovery is certain to continue, with further additions to our treatment armamentarium.
New blood-based screening tools will soon become standard, and similar methodologies will be applied in treatment monitoring and surveillance, with highly sensitive methods to detect measurable residual disease. The latter will increase cure rates in the adjuvant setting by guiding patient and treatment selection, and at the time of recurrence through identification of low-volume, curable, disease. Therapeutic personalization will continue to advance with new “omic” signatures to guide treatment. Tumor resistance to cellular therapies and immunotherapies will be solved—and even advanced solid tumors will be curable. I imagine that, just as care has moved from the inpatient to the outpatient setting, we will see many patient visits migrating to the use of telemedicine. And the expanding survivor population will require new care delivery models to meet the needs of long-term follow-up.
The onslaught of new data from clinical trials and high-quality observational real-world data sources is already overwhelming. We must find new ways to synthesize these research data along with the rich clinical data for each individual patient. In the foreseeable future, automated systems will be in place to organize and curate clinical data and apply published evidence and benchmarking from national pooled sources to provide decision support. The value of high-quality data entry at the point of care will be increasingly recognized, including key structured data elements, and associated opportunities for data-sharing, pooled analyses, and benchmarking. New data sources will become routine, including remote monitoring using digital health applications and patient-reported information. Accessibility of patient data across sites of care for clinical and research purposes will be facilitated by technical interoperability and adoption of common data models. There will be continued advances in artificial intelligence, but clinical decisions will continue to reside with human experts, supported by machine algorithms.
Improving the Design and Conduct of Clinical Trials
The generation of high-quality evidence to guide treatment requires that clinical trials be attractive to patients, widely accessible, and conducted efficiently. This will be achieved with the application of technology to improve patient identification for studies and the increased utilization of electronic health records (EHRs) to centralize data collection and monitoring. The clinical trials of the future will leverage data in the EHR collected during routine clinical care, supplemented by intentional collection of additional data elements required to ensure the quality and completeness needed to address specific research questions.
Building upon current efforts, clinical trial inclusion criteria will be simplified and expanded so that patients enrolled in clinical trials are more representative of the true, broader patient populations. Novel study designs will incorporate real-world data as control populations to increase efficiency and attractiveness by minimizing the proportion of patients randomly assigned to control arms. Ultimately, clinical research will be conducted wherever care is delivered.
Fifteen years after the National Cancer Act was enacted, I was a student in medical school, drawn to the field of oncology by the power of the patient relationships I observed and experienced and the application of science to advancing patient care. Those features still hold today in our highly personal and dynamic field, and I expect they will continue to do so in the next 50 years.
DISCLOSURE: Dr. Meropol is an employee of Flatiron Health, an independent subsidiary of the Roche Group, and holds equity interests in Flatiron Health and Roche.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
REFERENCES
1. Siegel RL, Miller KD, Fuchs HE, et al: Cancer statistics, 2022. CA Cancer J Clin 72:7-33, 2022.
2. National Cancer Institute: Cancer Statistics. Available at www.cancer.gov/about-cancer/understanding/statistics. Accessed on February 11, 2022.
3. U.S. Food and Drug Administration: Novel Drug Approvals for 2021. Available at www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021. Accessed February 11, 2022.
Dr. Meropol is Vice President of Research Oncology at Flatiron Health.
