Viewpoints Debate Merits of Universal Tumor Sequencing

By Lori Solomon, Editor, Diagnostic Testing & Emerging Technologies

There is universal recognition that genomic information has forever changed oncology care and is increasingly driving treatment decisions. For patients who have exhausted standard therapy or with rare tumors, there is growing consensus that genomic testing is appropriate. However, debate remains about the utility of implementing universal tumor sequencing, as seen in two opposing viewpoints published April 14 in JAMA Oncology.

“In this era of massive database creation, knowing the genomics of thousands or millions of patients and their subsequent outcome will undoubtedly provide transformative information for successfully treating cancers,” writes Vivek Subbiah, M.D., from University of Texas MD Anderson Cancer Center in Houston, in advocating for universal tumor sequencing. “Most important, however, genomic testing provides a powerful diagnostic tool, and every patient with cancer deserves an accurate diagnosis.”

Neither side would dispute that established targets benefit treatment for many solid and hematologic cancers. The difference is whether or not these single-gene, single-drug or hotspot tests are sufficient, or whether testing should shift towards more comprehensive, multiplex methods (pan-cancer or next-generation sequencing-based testing). Subbiah argues that comprehensive testing has advantages of not wasting tissue, saving money, compared to pricing numerous individual tests, and creating a thorough genomic information portfolio.

Others question the value of comprehensive genomic information in terms of improved patient outcomes.

“When evaluating any new intervention, we rightfully expect to see trial data that demonstrate improvement in a prospectively defined, clinically significant end point measured in a population of patients who receive the novel approach compared with those who are managed by current standards of care,” writes Howard West, M.D., from the Swedish Cancer Institute in Seattle, Wash. “Though precision medicine is a buzz-worthy catchphrase, it falls woefully short by these criteria.”

West argues that too many genomic studies focus on the “manufactured end point” of detecting a targetable mutation, a “low water mark of correlation” compared to “meaningful end points” of patient outcomes. He suggests that such studies run the risk of translating correlation into “implied and imagined” meaningful outcomes.

“Without knowing how many patients undergo molecular testing beyond current standards, we should view cases of a remarkable response to a targeted therapy identified by tumor sequencing as lottery winners rather than as evidence to support its use as a strategy for routine clinical decision making,” cautions West. “Such cases offer hope the same way a scratch ticket provides hope for those seeking to win an instant fortune. Without population-based data illustrating significant benefits of a sustained duration from tumor sequencing versus standard management … we might reasonably surmise that unproven treatments directed by tumor sequencing will generate endless opportunities for clinicians to follow rabbit holes of speculative but ineffective and wildly expensive alternatives.”