Precision oncology has transformed cancer care, but it also raises complex ethical questions around safety, informed consent, access, equity, and genomic privacy. In this expert panel discussion from the Precision Oncology Summit, Stanford bioethicist Henry T. Greely, JD, joins practicing oncologists to examine how clinicians and health systems navigate these challenges in real-world practice.

From Left to Right, Henry T. (Hank) Greely, JD, Sachdev P Thomas, MD, Meera Ragavan, MD, and Alborz Alali, MD.

This video shows a short presentation followed by a roundtable discussion at the Precision Oncology Summit, highlighting complex challenges complex ethical challenges that practitioners must navigate daily in the field of precision oncology, which brings tremendous promise for cancer treatment. While none of these challenges represent fundamental obstacles to the advancement of precision medicine, they demand careful attention and thoughtful approaches from clinicians, researchers, and healthcare systems alike.

The discussion was opened by Professor of Law and Director of Stanford Program in Neuroscience and Society, Henry T. (Hank) Greely, JD (Stanford Law School). The panelists include Sachdev P Thomas, MD (Kaiser Permanente), Meera Ragavan, MD (Kaiser Permanente), and Alborz Alali, MD (Dignity Health Woodland Clinic).

The transcript below has not been reviewed by the speakers and may contain errors.

The Foundational Ethics in Precision Oncology: Safety and Efficacy

The most fundamental ethical obligations in precision oncology—though often overlooked as ethical issues—center on safety and efficacy. Nothing is more unethical than exposing patients to unreasonably unsafe treatments or offering them ineffective interventions. In precision oncology, efficacy presents particularly complex challenges.

The field encompasses a wide spectrum of outcomes. Some diseases, like chronic myeloid leukemia (CML), have experienced near-miraculous improvements through precision approaches. However, many other cancers have seen little to no benefit, with numerous cases falling somewhere in between. The parameters governing these outcomes shift rapidly, creating both opportunities and responsibilities for clinicians.

This rapid evolution creates a wonderful opportunity to relieve human suffering, but it comes with the burden of staying current. The challenge intensifies because precision oncology operates in percentages and probabilities. Clinicians make decisions based on group statistics that cannot fully account for individual patient factors—environmental history, broader genomic background, or the heterogeneity within a tumor's genome. The ethical imperative to maintain current knowledge becomes particularly acute in such a fast-moving field with potential for significant patient impact.

A related concern involves the "hammer and nail" problem. When specialists focus intensively on one approach, they risk viewing every problem through that single lens. While precision oncology represents one important front in the fight against cancer, it exists alongside immunotherapy and other emerging treatments. Recent findings, such as the correlation between mRNA COVID vaccination and improved survival in small-cell lung cancer and melanoma, highlight how quickly new insights can emerge. Although early and speculative, such developments underscore the importance of remaining open to diverse approaches beyond one's primary area of expertise.

The Challenge of Informed Consent in Complex Decision-Making

The complexities that make precision oncology challenging for clinicians make informed consent even more difficult for patients. If the decision-making framework proves complicated for trained specialists, it becomes exponentially more challenging for patients, many of whom struggle with statistical reasoning—a fact evidenced by lottery participation rates.

Oncology patients face informed consent under particularly difficult circumstances. They often arrive terrified, confronting not only fears of mortality and morbidity but also lingering cultural stigmas surrounding cancer diagnoses. These emotional burdens complicate decision-making when treatment options involve unclear, uncertain statistical choices.

The challenge deepens when patients desperately seek hope in seemingly hopeless situations. Marketing from pharmaceutical companies and testing laboratories—directed both at physicians and, through television and social media, directly at patients—adds another layer of complexity to the informed consent process. Ensuring that patients understand their options well enough to make collaborative decisions remains an ongoing and particularly demanding challenge in this field.

Access Disparities: Financial, Geographic, and Population-Based

Access to precision oncology involves multiple dimensions of inequality, each raising distinct ethical concerns. Financial barriers remain significant—questions of insurance coverage, payer policies, and the struggle to obtain approval for treatments that clinicians and patients believe offer the best chance of success create ongoing challenges.

Geographic access presents another barrier. Large portions of the United States lack specialists knowledgeable about precision oncology within 100 or even 200 miles. On a global scale, most of the world's population lives more than 500 miles from such expertise. Even if precision oncology became widely available financially and geographically in developed nations, residents of rural Bolivia, the Central African Republic, or Laos would likely wait decades for similar access.

While focusing on national access issues makes sense given that the United States has yet to guarantee healthcare to all its residents, the international implications prove even more significant. This connects to another critical access problem: the field relies on human population genetics that vary by geography, yet the underlying data derives predominantly from people of European descent. Approximately 80 to 85 percent of genomic data comes from individuals whose ancestors originated in Europe, often Northern Europe specifically. While genetics doesn't determine everything, it matters significantly, and different genetic variations produce different effects across populations.

Improving database coverage to ensure diverse populations receive equal opportunities for health and successful treatment represents a major ethical imperative. The access question has another dimension as well. While the ethical goal remains ensuring everyone who needs precision oncology receives it, the corollary proves equally important: those unlikely to benefit shouldn't receive it.

In diseases with high fatality rates and limited treatment options, pressure mounts for access to drugs even when patients don't meet FDA labeling requirements or literature-supported criteria for off-label use. Patients without other options naturally seek access driven by hope, but providing treatments unlikely to help serves neither patients nor the healthcare system. Increasing appropriate access while serving as a responsible gatekeeper to deny inappropriate access creates a delicate ethical balance, complicated further by safety concerns with some denied treatments.

Privacy Concerns in the Genomic Era

Privacy issues, while perhaps less critical than other challenges, matter significantly to patients. For fifty years, the public has heard that genes are special, magical, representing the essence of individual identity. Many believe that if someone obtains their genome, terrible consequences will follow.

In reality, genome data may be less sensitive than Google search records or credit card information. Most genomes contain nothing particularly interesting. However, many people believe their genomes hold fascinating, unique, important, or scary information they want protected from others. Although precision oncology tests typically involve targeted genomic segments rather than whole genome sequencing, patients worry nonetheless.

Clinicians should inform patients about the Genetic Information Nondiscrimination Act (GINA), which prohibits employment and health insurance discrimination based on genetic information at the federal level. They should also reassure patients that genetic information is less sensitive than commonly believed and unlikely to significantly impact their lives even if leaked. However, complete confidentiality cannot be guaranteed. Hackers represent a persistent threat, and law enforcement authorities could potentially obtain genetic information through subpoenas or search warrants for forensic purposes, leaving healthcare providers with little recourse.

While complete privacy cannot be promised, patients should understand that genetic information breaches shouldn't create major problems in most circumstances.

Dr. Alali on Confidentiality vs. Family Right to Know

A real clinical case illustrates the complex intersection of patient autonomy, confidentiality, and family welfare. A 35-year-old woman diagnosed with triple-positive BRCA1-positive breast carcinoma requiring chemotherapy, radiation, and surgery faced a profound dilemma. She has an identical twin sister from whom she has been estranged for years following a contentious inheritance dispute that involved attorneys and harsh words before settling into silence.

When informed that her identical twin faces the same genetic risk, the patient experienced devastation. This situation creates tension for everyone involved. The patient faces an emotional and ethical crisis, while the oncologist and genetic counselor must balance confidentiality and patient autonomy against another person's right to potentially life-saving information.

While this scenario represents an outlier, studies show 85 to 95 percent of patients share genetic information with immediate family. It offers valuable lessons about physician-patient relationships and institutional policy development. Such cases, though uncommon, require clear procedures for navigating the tension between autonomy, confidentiality, and the right to know crucial health information. Identical twins represent approximately one in 210 live births globally—a remarkably stable rate across cultures—meaning nearly one percent of the world's population belongs to an identical twin pair, making such scenarios more likely than they might initially appear.

Dr. Thomas on Daily Clinical Challenges in Precision Oncology Practice

From a practicing medical oncologist's perspective, precision oncology presents numerous day-to-day ethical challenges. Within integrated healthcare systems like Kaiser Permanente, structured approaches exist for reviewing all genomic results, including next-generation sequencing (NGS) from both liquid and tissue samples, with particular attention to incidental germline findings.

Common mutations like BRCA1, BRCA2, and CHEK2 may be purely somatic, but efforts are made to inform physicians when findings may be germline, warranting referral to genetics programs. Robust genetics divisions can assume responsibility for patient discussions, germline testing, and even cascade testing for family members and relatives when needed.

However, challenges persist. Families may be estranged or geographically dispersed. Relatives may lack means, access, or insurance coverage for germline testing or face denials. These obstacles remain ongoing concerns.

Regarding testing rates, NGS and sequencing have increased but remain uneven—approximately 80 percent in academic practices, 50 to 55 percent in semi-urban private practices, but only 35 percent in rural communities. These numbers have remained relatively static, though practicing oncologists increasingly recognize the importance of early testing.

Approval process nuances create additional challenges. RET inhibitors, for example, have pan-tumor approval for fusions, but point mutations in medullary thyroid carcinoma can also respond—information clinicians must know. Similar situations arise with cholangiocarcinoma and FGFR2 inhibitors. Drugs like Pemigatinib from the FIGHT trial and Futibatinib from the Phoenix trial are approved for rearrangements. Second-generation drugs like Tinetinib from Tera Pharmaceuticals are being tested for FGFR2 mutations and other alterations, but these remain under investigation. Instances occur where drugs are used inappropriately because the specific indication—fusion rearrangements in these cases—isn't clearly understood.

Issues also arise around homologous recombination deficiency (HRD) in ovarian cancer, particularly in determining loss of heterozygosity and appropriate thresholds. Loss of heterozygosity thresholds for ovarian cancer likely differ from those for prostate cancer, where it may not be considered. Paired sampling can reveal discrepancies—a recent case involved a germline RAD51 mutation that tissue sequencing missed due to a large exon deletion. These details sometimes prove critical.

This raises questions about optimal testing approaches—tissue versus liquid biopsies. For ESR1 mutations, liquid tumor testing makes perfect sense. However, for MTAP deletions, liquid biopsies likely miss most cases, making tissue sampling preferable.

Test utility varies by disease. Pancreatic cancer historically saw low testing rates due to limited actionable findings, but this is changing. As KRAS-ON trials evolve and rapid accrual in trials like KRYSTAL demonstrates, identifying specific KRAS mutations—G12A, G12C, G12S, or G13D—becomes important because treatments differ.

These challenges require ongoing education, but the field as a whole continues evolving, with oncologists demonstrably improving their precision medicine expertise.

Dr. Ragavan on Policy and Payer Landscape Implications

From a health services research perspective focused on structural and financial barriers at Kaiser, precision oncology's intersection with current policy and payer landscapes reveals important trends. Two major developments stand out.

First, precision oncology has driven a clear pattern: we're testing more and treating more. Testing expansion ranges from multi-cancer early detection (MCED) tests becoming mainstream to pan-tumor approvals, new driver identification, and minimal residual disease (MRD) testing post-operatively. The field is expanding rapidly, along with the resulting therapeutics.

This expansion has transformed outcomes for some patients, created marginal benefits for others, and, in some cases, may not have achieved desired results or potentially caused harm. Acknowledging this spectrum remains important. The critical question becomes: how do health systems adapt to these rapid changes?

Incorporating new tests into workflows—such as HER2-IHC with pan-tumor approval or MET-IHC, now approved across tumor types for thoracic oncology—presents constant challenges. Every few months brings new tests and diagnostics requiring integration into routine workflows. Additionally, as more early-stage patients receive extended treatments, pressure increases on already resource-strained systems. Infusion volumes and demand rise across health systems while oncologist supply may decline, creating concerning mismatches from a health system perspective.

The second major trend involves a rising cost and coverage crisis in the United States affecting patient, system, and payer levels. Not all payers still cover guideline-concordant treatments, with well-described lags causing significant practice difficulties. While California is an exception, many states lack Medicaid programs covering comprehensive NGS for tumor types like lung cancer, despite guideline inclusion for over five years.

As care becomes increasingly expensive, payers shift costs to patients. After several relatively flat years, deductibles are expected to rise substantially in the coming year, with healthcare teams actively helping patients navigate open enrollment changes.

Some changes are policy-driven. Dramatic Medicaid changes begin in 2027. Enhanced premium tax credits on Affordable Care Act plans that increased enrollment during COVID are expiring—currently central to government shutdown debates. However, many changes are payer-driven and employer-driven, as unsustainable costs drive up premiums, deductibles, and cost-sharing across the board.

This creates ethical dilemmas. As testing and treatment expand while access issues persist, the reality emerges that in the United States—setting aside global considerations—some patients receive comprehensive testing despite not being candidates for systemic therapy (perhaps older, frail patients), while simultaneously, younger patients eligible for clinical trials targeting driver mutations without FDA-approved therapies don't even receive the comprehensive NGS needed to facilitate trial enrollment.

This represents the reality within which practice occurs, an important context for considering precision oncology's ethical landscape. The estimated cost of adequate health insurance for a family of four reached $27,000 in the past year, against an average household income of approximately $80,000. While much of this doesn't come from take-home pay, it represents a substantial burden with no improvement anticipated in the near future.