Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many peo­ple around the world, my life has been pro­found­ly shaped by can­cer. Those per­son­al ex­pe­ri­ences, along with a deep love of clin­i­cal lab­o­ra­to­ry sci­ence and a pas­sion to ap­ply the pow­er of ge­nomics in med­i­cine, mo­ti­vat­ed me to launch a com­pa­ny that would im­prove can­cer care through bet­ter di­ag­nos­tics. Thir­teen years lat­er, I am proud that we are de­liv­er­ing more ac­cu­rate in­for­ma­tion at mul­ti­ple points along the pa­tient jour­ney, with a fo­cus on eight of the 10 can­cers that are most com­mon­ly di­ag­nosed in the Unit­ed States.

Two per­son­al anec­dotes il­lus­trate the need for more ef­fec­tive di­ag­nos­tic tests. My fa­ther, who had stage 4 lung can­cer, died from com­pli­ca­tions of a nee­dle biop­sy pro­ce­dure con­duct­ed to con­firm his can­cer di­ag­no­sis. Fol­low­ing the pro­ce­dure, he ex­pe­ri­enced a col­lapsed lung, a very un­for­tu­nate but po­ten­tial out­come from this type of in­va­sive pro­ce­dure. He was put on a ven­ti­la­tor that day and died two weeks lat­er. If that’s not a call for less in­va­sive di­ag­nos­tic test­ing, I don’t know what is.

My hus­band was al­so di­ag­nosed with lung can­cer. His doc­tor rec­om­mend­ed a proac­tive screen­ing pro­gram even though he’d quit smok­ing 25 years ear­li­er. The first CT scan re­vealed very small nod­ules. We went back every six months for new scans un­til one day the doc­tors said, based on nod­ule growth and im­age fea­tures, it was very like­ly he had can­cer. They per­formed surgery to re­move the mid­dle lobe of his lung. He nev­er need­ed ad­di­tion­al treat­ment, and five years lat­er he was can­cer-free. It’s a com­pelling ex­am­ple of the dif­fer­ence an ear­ly di­ag­no­sis can make.

These and so many oth­er re­al-world cas­es serve as a con­stant re­minder that we in the di­ag­nos­tics field must fo­cus on de­vel­op­ing clin­i­cal tests that mat­ter — tests that ad­dress re­al health­care needs. Whether it’s ac­cel­er­at­ing an ac­cu­rate di­ag­no­sis, de­liv­er­ing more ac­tion­able in­for­ma­tion, pro­vid­ing a less in­va­sive op­tion, or guid­ing treat­ment de­ci­sions, every di­ag­nos­tic test should stream­line and im­prove the pa­tient jour­ney in some way. This should be a guid­ing prin­ci­ple as we strive to demon­strate the clin­i­cal val­ue of ge­nom­ic di­ag­nos­tics.

A Com­mit­ment to Can­cer Di­ag­nos­tics

When we found­ed Ve­r­a­cyte, our goal was to im­prove the di­ag­nos­tic path­way in a broad range of can­cers. At that time, biop­sies based on any­thing oth­er than sol­id tis­sue of­ten led to di­ag­noses that were un­ac­cept­ably am­bigu­ous. Too many peo­ple were un­der­go­ing in­va­sive pro­ce­dures to try to get a clear­er di­ag­no­sis or be­ing treat­ed with un­nec­es­sary surg­eries for growths that were be­nign. This isn’t news to any­one in the di­ag­nos­tics field to­day, of course, but at the time the in­sight gave us a clear path for­ward.

Since then, we have fo­cused on min­ing rich ge­nom­ic da­ta sets and us­ing so­phis­ti­cat­ed analy­ses to build mol­e­c­u­lar clas­si­fiers that can help rule can­cer in or out more quick­ly, or help de­ter­mine how best to treat the pa­tient. From thy­roid to lung to prostate can­cer and many oth­ers, we now pro­vide mul­ti­ple tests that re­duce un­cer­tain­ty and in­form next steps at sev­er­al points in the pa­tient jour­ney, in­clud­ing prog­nos­tic and treat­ment-in­form­ing tests.

There are still so many ways for clin­i­cal di­ag­nos­tics to evolve and add even greater val­ue along the pa­tient jour­ney. Even the most cut­ting-edge tests avail­able to­day can prob­a­bly be made bet­ter — from less in­va­sive sam­ple types to in­cor­po­rat­ing more da­ta.

Lung can­cer is a prime (and time­ly) ex­am­ple. The need for a non­in­va­sive test to im­prove ear­ly lung can­cer de­tec­tion is ur­gent. Ap­prox­i­mate­ly 1 mil­lion peo­ple are sent to the pul­mo­nolo­gist each year due to sus­pi­cious lung nod­ules, and we ex­pect that num­ber to grow since the U.S. Pre­ven­tive Ser­vices Task Force re­cent­ly ex­pand­ed its rec­om­men­da­tions for who should get lung CT screen­ing. The vast ma­jor­i­ty of lung nod­ules are be­nign. Un­for­tu­nate­ly, many peo­ple at low risk of can­cer un­der­go in­va­sive pro­ce­dures, while those with can­cer may ex­pe­ri­ence de­layed di­ag­no­sis and treat­ment, be­cause physi­cians lack stan­dard and ob­jec­tive tools to help them de­ter­mine the like­li­hood that any giv­en nod­ule is can­cer­ous.

Lat­er this year, we will launch a new test that can im­prove ear­ly lung can­cer as­sess­ment based on a sim­ple nasal swab. Clin­i­cal val­i­da­tion da­ta for the first-of-its-kind Per­cep­ta Nasal Swab test was pre­sent­ed re­cent­ly at the 2021 Amer­i­can So­ci­ety of Clin­i­cal On­col­o­gy (AS­CO) An­nu­al Meet­ing. The test us­es ad­vanced ge­nom­ic and es­tab­lished “field of in­jury” tech­nol­o­gy to de­tect smok­ing-re­lat­ed dam­age as­so­ci­at­ed with lung can­cer in cur­rent or for­mer smok­ers with sus­pi­cious lung nod­ules us­ing a sam­ple col­lect­ed from the nasal pas­sage. It is based on a mol­e­c­u­lar clas­si­fi­er de­vel­oped with whole-tran­scrip­tome RNA se­quenc­ing da­ta gen­er­at­ed from a train­ing set of more than 1,100 nasal sam­ples. The 502 genes se­lect­ed for the fi­nal al­go­rithm give op­ti­mal sen­si­tiv­i­ty and speci­fici­ty and were val­i­dat­ed in an in­de­pen­dent set of near­ly 250 pa­tient sam­ples col­lect­ed across 25 clin­i­cal sites. The test can ac­cu­rate­ly clas­si­fy pa­tients as low, in­ter­me­di­ate or high risk, en­abling physi­cians to take a da­ta-dri­ven ap­proach for rec­om­mend­ing rou­tine mon­i­tor­ing or more ag­gres­sive pro­ce­dures.

Based on what we have seen with our mol­e­c­u­lar clas­si­fiers for oth­er types of can­cer, we be­lieve this nasal swab test will help pa­tients with be­nign nod­ules avoid un­nec­es­sary, cost­ly and po­ten­tial­ly life-threat­en­ing surg­eries – and will en­able faster di­ag­no­sis and treat­ment for those pa­tients with can­cer. When I con­sid­er what my fa­ther went through, or even the anx­i­ety my hus­band and I ex­pe­ri­enced wait­ing for the re­sults of each new scan, I am en­cour­aged by the abil­i­ty of this non-in­va­sive nasal swab to pro­vide ini­tial an­swers and think it will be game-chang­ing.

Demon­strat­ing Val­ue

The clin­i­cal di­ag­nos­tics com­mu­ni­ty has strug­gled to get oth­er health­care stake­hold­ers to val­ue di­ag­nos­tic test­ing. Even as more and more care de­ci­sions are be­ing guid­ed by di­ag­nos­tic re­sults, our tests have been un­der­ap­pre­ci­at­ed in the broad­er med­ical com­mu­ni­ty.

For­tu­nate­ly, I be­lieve we are fi­nal­ly at an in­flec­tion point, dri­ven large­ly by the COVID-19 pan­dem­ic. This glob­al health cri­sis high­light­ed the crit­i­cal role med­ical test­ing plays not on­ly in our health but al­so in our lo­cal and glob­al economies, and it gave di­ag­nos­tic test de­vel­op­ers and clin­i­cal lab­o­ra­to­ries long-over­due recog­ni­tion. There is an op­por­tu­ni­ty right now — while the iron is still hot — to ed­u­cate physi­cians, in­sur­ers, gov­ern­ment agen­cies and the gen­er­al pub­lic about the im­por­tance of clin­i­cal di­ag­nos­tics in all ar­eas of health.

The onus will be on us, though, to demon­strate the val­ue of these tests. Not all tests are wor­thy of rou­tine med­ical use. Those that are should be but­tressed by ro­bust clin­i­cal val­i­da­tion stud­ies and oth­er da­ta to show the ad­van­tages they of­fer in stream­lin­ing clin­i­cal de­ci­sion-mak­ing, im­prov­ing pa­tient out­comes, and re­duc­ing health­care costs.

Bon­nie H. An­der­son is co­founder and ex­ec­u­tive chair­woman of Ve­r­a­cyte, a glob­al ge­nom­ic di­ag­nos­tics com­pa­ny that im­proves pa­tient care by pro­vid­ing an­swers to clin­i­cal ques­tions that in­form di­ag­no­sis and treat­ment de­ci­sions.