Growing pains put gene panels in a pinch

Says Dr. Lindeman, “I’ve had payers tell me they’re not interested in paying for things that are in the WHO diagnostic guideline if it doesn’t lead to a change in treatment.”

Dr. Lindeman also sees a gap between how pathologists and treating physicians interact with guidelines. He would like to see the NCCN expand its scope to include a set of algorithms and guidelines for diagnostic workups, done in parallel with, or anticipation of, what needs to be done for management. It would be helpful, he adds, if more pathologists were involved in creating the NCCN guidelines. “There’s usually a few. I don’t want to complain that there’s no voice. But it’s usually a minority.”

But if the underlying problem is economic, even the best guidelines will only go so far, Dr. Caughron says. Not only is it hard for guidelines to keep up with the published literature, but, more concerning, he says, “is there seems to be a reluctance on the part of payers to look to guidelines as a definitive answer to their questions. I have heard payers speak with cynicism about guidelines, which I find disappointing and a little disturbing.” Guidelines can help physicians deliver the right care, but they might not push the payment needle.

Why the cynicism? “Not all guidelines are created equal, if I can put it that way,” says Dr. Caughron. Some are better researched and written than others. “It only takes one less than perfect example for someone who’s writing the checks and paying the bills to believe that these can be dismissed.”

There’s another problem: Payers aren’t steeped in practice patterns and realities, patient care trends, and technologies the way health care providers are. Guidelines don’t map directly onto what happens in practice, and thus can’t fully answer the questions payers may have when deciding what to pay for.

“A great example of that is prior authorization,” Dr. Caughron says. While guidelines make it clear that certain testing should occur with NSCLC, for example, payers may say, “‘We agree, but we want to review these charts, these patients, and make sure they meet the criteria,’” rather than trusting the system.

No one talks about taking economics off the table when pondering these problems—clearly, economics is the table on which other laboratory challenges are set.

But there is room around that table to work out some answers, Dr. Chandra says. “Medicine is practiced at the local level,” he says.

PathGroup has its own high-volume, high-throughput molecular laboratory, providing services to more than 200 hospitals belonging to integrated regional health care systems spanning multiple states. “We have different testing protocols that are institution-specific.” Those most involved with genomic profiling—pathologists, medical oncologists, interventional pulmonologists, interventional radiologists, genetic counselors, hospital administrators—identify standards of care and appropriate testing protocols at each hospital.

Equally important, Dr. Chandra says, is they agree on who will order the testing.

In some cases, that might be pathology-driven reflex testing. This can be a standing order that’s arrived at through a consensus, multidisciplinary conversation. It could also be an institution-specific order, Dr. Chandra says. “In one of our institutions, every stage three and stage four lung cancer gets molecular testing based on medical and NCCN guidelines.” In other institutions, oncologists and pathologists can simply order molecular testing ad hoc.

However, the ad hoc approach appears to be less successful, Dr. Chandra says. “In our experience, either testing doesn’t get ordered or it doesn’t get ordered quickly enough. And oftentimes the pathologist will wait for the oncologist, and the oncologist will wait for the pathologist—and the test never gets ordered.” The literature also backs up the efficacy of multidisciplinary approaches and developing local protocols, he says.

“I’ve always been a proponent of pathology-driven reflex testing,” Dr. Chandra says, adding that a growing literature suggests it leads to more improved identification of actionable biomarkers, shorter time to treatment, and better outcomes.

“What can’t be done is nothing,” Dr. Chandra says. “That is just unacceptable.”

Dr. Caughron is also a fan of pathologists initiating the testing at the time they identify a malignant tumor, though he notes some can be reluctant to take that step. “In many environments the pathologist says, I don’t feel comfortable doing that because I’m only doing the analysis to guide this specific treatment. And since I’m not the one treating the patient, I’ll wait for the oncologist to order the testing.” In some cases, he says, the pathologist might not know, at the time of diagnosis, who the treating oncologist will be, adding to delays.

Pathologists might also pause knowing that the testing is expensive and may not be covered. “We’re going to wait and only do it in certain environments, or for certain conditions.” They may also encounter delays with the uptick in prior authorization requirements.

MAWD Pathology Group has more than 50 pathologists spread over three states. “In each environment it plays out a little differently in terms of how the local care team best sees biomarker testing implemented,” Dr. Caughron says.

Echoing Dr. Chandra as well as the literature, Dr. Caughron suggests the most successful approach uses pathologist-initiated testing. At some MAWD sites, however, oncologists have stated a clear preference for ordering the tests themselves; at others, the pathologist orders it at the time of diagnosis.

There are times when everyone agrees (at, say, a tumor conference) that biomarker testing should be done. In those situations it’s often a send-out test, and the pathologist might not be compensated for pulling the block, reviewing the slide, and sending it out. And when the results do come back, the pathologist may be left out of the loop.

If the past was characterized by the town-gown divide, these days nearly everyone, pathologists and oncologists alike, has shed their gowns and entered the town, given the rapid advances in molecular pathology.

Simply put, it’s hard to keep up. “It’s hard for me to keep up,” says Dr. Chandra. “And I’m specifically trained and boarded in molecular pathology.”

PathGroup has expanded its efforts to centralize the educational information that goes out to its enterprise network of 240 pathologists, with a team of locally based physicians and scientists developing evidence-based recommendations, to help standardize testing protocols across institutions.

Other challenges are also evergreen, including collecting sufficient tissue or plasma, deciding whether to initiate treatment while waiting for testing, and reviewing test results.

In the latter case, Dr. Chandra says, “Many next-generation sequencing providers give you a 15-page report with all the alterations detected.” The message, if not the actual wording, he says, is, Here you go—you all figure out what to do with it. Good luck!

PathGroup tries to get a handle on that via its molecular tumor boards across its enterprise network, which meet virtually twice a month. Dr. Chandra and his colleague Michelle Shiller, DO, lead the sessions—she’s PathGroup’s medical director of genomics and molecular pathology services, based at Baylor University Medical Center in Dallas—which are now being offered for CME credit.

“It’s a somewhat decent solution,” says Dr. Chandra, “but how do we scale that effort? It needs to be driven by a champion on the oncology side and a champion on the pathology side.”

As for the lengthy reports themselves, PathGroup spent several years gathering input from its community oncologists about what they liked and disliked in NGS reports, then designed a report that was implemented when PathGroup launched its FDA-cleared Endeavor assay in May 2020, Dr. Chandra says. “All the relevant information that an oncologist will need is condensed to one page.”

The most actionable alterations are placed prominently on the front page, where the biomarker result is listed along with potential therapies, organized according to the strength of medical evidence. The report lists clinical trials that might be appropriate for the patient. Also included are sections for tumor mutational burden, microsatellite instability, and pertinent negatives.

Dr. Chandra also points to another feature of the reports: two or three paragraphs written by a team of molecular professionals including board-certified PhD directors and physicians, then reviewed, edited, and signed out by a molecular pathologist. The text provides a summary of the diagnostic, prognostic, and/or therapeutic significance of the results. It’s particularly helpful, he says, when two results suggest opposing information—for example, finding an EGFR exon 19 deletion that would indicate treating with an EGFR inhibitor, as well as high PD-L1 expression, which would suggest using immunotherapy.

“The NCCN guidelines will tell you to prioritize the EGFR mutation over the immunotherapy in those contexts,” Dr. Chandra says. “So we take that effort out and reconcile those differences, speaking to the clinical utility in our report. We made a lot of effort to design it in a way that is most meaningful and optimal to the oncologists,” enabling them to quickly understand the therapeutic strategy for their patients.

Is Dr. Lindeman surprised by how the field has played out? Not particularly, he says, before adding, “It’s disappointing, to be sure.”

Yet he and others sound more optimistic than resigned when they contemplate the work that lies ahead. “It sounds kind of ‘apple pie,’ but everything comes back to communication,” Dr. Lindeman says. “Pathology shouldn’t be making decisions or formulating opinions without input from our [oncologist] colleagues. And vice versa.”

He says that worked well at his former institutions in Boston. He met every couple of weeks with the clinical and academic research leaders to discuss what was emerging in their work. “I knew what was coming, and they knew our issues in the lab, and we worked together.”

Like so many others, Dr. Lindeman notes the pandemic took its toll on some of those routines. “A lot of that communication suffered, to be perfectly honest. But we still tried to be partners with our oncologists, as opposed to contractors for them.”

Molecular testing for cancer slowed down considerably at the height of the pandemic, he says, because the laboratory had to divert resources to viral testing.

With the crisis-mode portion of the pandemic now receding, it might be easy to settle into a lower intensity routine. Sometimes, he concedes, “it’s easier to be a contractor. We might just want to do our work and get paid and move on, and maybe they just want to pay us and not interact on a different level.

“But one of the problems for pathology in general,” Dr. Lindeman continues, “is that our specialty has become a little transactional in that regard with our colleagues. It’s important for us to be active consultants and contribute to patient care decisions at all of our institutions, and to demonstrate our value beyond just the testing and the microscopy. But we also need to be advocates for overall care, and for ourselves in the process.”

He pauses, then says: “I gave a speech; I didn’t mean to. But for me, that’s what works.”

He continues: “Many people are doing this, so I don’t want to make it sound like I’m the only person who’s thought of it—far from it.” But his emphasis is clear: “This is an important part of our career and our role in medicine that we shouldn’t give up.”

Karen Titus is CAP TODAY contributing editor and co-managing editor.