Comprehensive Genomic Profiling at Diagnosis Extends Survival in Patients with Advanced Cancer

A new study from Providence Health presents a strong case for integrating complete genomic testing into the early stages of cancer diagnosis, arguing that doing so can significantly improve patient outcomes. Published this week in JCO Oncology Practice, the study demonstrates that implementing genomic profiling as part of the initial diagnostic workup can streamline treatment and increase access to precision therapies that substantially extend survival.

Led by co-authors Brian Piening, PhD, and Carlo Bifulco, MD, the research includes a cohort of more than 3,200 advanced cancer patients across the Providence Health network, spanning states including California, Oregon, Washington, and Texas.

The study comes amid the consensus that cancer treatment should ideally be tailored based on a patient’s specific genetic mutations. However, Piening and Bifulco observed that many cancer patients do not receive timely genomic testing, often missing critical opportunities for personalized treatments that could improve their prognosis. “One of the big issues in the field is a lot of patients don’t get access to this,” Piening said. “They cannot likely get a precision medicine path if they don’t get the testing upfront.”

Addressing barriers to genomic testing

The team began developing the study over five years ago to tackle obstacles to genomic testing, including insurance denials, delays in results, and inconsistencies in the types of tests administered. “We built a project where genomic testing for advanced cancer patients would be instituted as early as possible,” Piening explained. By initiating testing at the point of diagnosis, the researchers aimed to ensure that treating oncologists would have a complete genomic profile in hand at the first meeting with their patients, maximizing the potential for informed, precision-guided treatment.

The new protocol established that every patient with advanced cancer would receive a comprehensive genomic panel test at no cost, covered by Providence Health. In contrast to the fragmented approach seen in many clinical settings—where only select gene panels or single-gene tests are ordered based on treatment decisions—the study used a comprehensive 523-gene DNA/RNA hybrid panel linked to advanced cancer. “We made it part of the pathologist’s initial workup,” Piening added. “This data can also help pathologists classify tumors, especially those of unknown origin.”

Bifulco emphasized that this early integration of genomic testing is crucial for patient care, describing the standard, delayed approach as “absurd” in light of modern advancements. “Cancer is a genomic disease, and to decouple genomic testing from the diagnosis of cancer in 2024 is, at this point, absurd,” he said. The study’s protocol, he argued, should be considered as routine as the standard pathological diagnosis performed under a microscope.

Earlier testing improved survival

The results of the first two years of this initiative support the approach. Over 49% of the patients tested had at least one actionable biomarker, meaning they could be matched with a targeted therapy, immunotherapy, or relevant clinical trial. Specifically, when assessing complete genomic profiling, 67% of tumors harbored actionable alterations including clinical trials, compared with 33% when tested with a 50-gene panel.

Among patients with six months or more of follow-up, over 52% received a targeted therapy or immunotherapy, versus 32% who received conventional chemotherapy alone. For patients who received a matched therapy based on their genomic results, the median survival rate increased to 25 months, compared to 17 months for those who received only chemotherapy.

This study follows the team’s first paper, focusing solely on advanced non-small cell lung cancer (NSCLC) patients. That analysis confirmed that comprehensive genomic profiling can provide critical, timely insights that inform treatment pathways  That study found that in comparison to small panel-tested patients, patients who received complete genomic testing had a higher rate of actionable mutations (77% vs. 63%), patients with actionable mutations received matched precision therapies at a higher rate (64% vs. 50%) and improvement in overall survival (median: 16 months vs. 7 months).

“When you add up molecular-guided therapies, immunotherapies, and clinical trials, it’s clear that comprehensive genomic profiling is pushing us toward better patient outcomes,” said Piening.

The authors hope their work will spark changes to make comprehensive genomic profiling a routine part of cancer diagnosis nationwide, similar to the diagnostic standards applied in hematologic cancers like leukemias and lymphomas, where genomic profiling has long been integrated into the initial workup. “There’s usually acceptance that the genomic workup is part of the diagnostic workflow for these blood cancers,” Bifulco noted. “But for solid tumors, this hasn’t been the case. We just need to change our approach.”

While incorporating genomic testing upfront may seem straightforward, the researchers acknowledge there are systemic barriers to overcome. One of the primary hurdles is shifting the healthcare framework to treat genomic testing as essential rather than elective, especially for solid tumors. By demonstrating the feasibility and benefits of this approach, the study provides a powerful case for establishing genomic profiling as a diagnostic standard. “Bringing it back to the pathologist as part of the initial diagnosis is the only way to overcome these gaps in patient care,” Bifulco said.

The economic benefits of this approach are also worth noting, as comprehensive testing at diagnosis could ultimately reduce the need for multiple, sequential tests over the course of treatment. By cutting down on fragmented testing and aligning patients with precision treatments earlier, the Providence model suggests potential savings and efficiencies across the healthcare system.

“We’re finally getting to a place where there’s such a spectrum of precision therapies available, that it’s making a clear impact on survival outcomes,” Piening said. The team plans to investigate additional subsets of patients and refine genomic testing strategies based on cancer type and other factors. “We expect to ask more specific questions as the data matures, looking at different tumor types and treatment patterns,” he said.

Ultimately, the study’s findings underscore the influence of complete genomic testing when applied early in a cancer patient’s journey. “Precision medicine has a lot of potential, but it only works if patients have access to it,” Bifulco emphasized.