nach oben

04.04.2024 | ORIGINAL ARTICLE

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments

verfasst von: Josef Rüschoff, George Kumar, Sunil Badve, Bharat Jasani, Emma Krause, Nathalie Rioux-Leclercq, Federico Rojo, Maurizio Martini, Liang Cheng, Maria Tretiakova, Catherine Mitchell, Robert A. Anders, Marie E. Robert, Darren Fahy, Mike Pyle, Quang Le, Limin Yu, Benjamin Glass, Vipul Baxi, Zulfia Babadjanova, James Pratt, Sergine Brutus, Maria Karasarides, Arndt Hartmann

Erschienen in: Virchows Archiv

Einloggen, um Zugang zu erhalten

Abstract

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20–30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28–8 assay. A 2-h training module on the 28–8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.

Nur mit Berechtigung zugänglich

Agilent Technologies (2021) PD-L1 IHC 22C3 pharmDx instructions for use. https://www.agilent.com/cs/library/packageinsert/public/P03951E_20.pdf . Accessed 27 Mar 2024

Agilent Technologies (2021) PD-L1 IHC 28–8 pharmDx instructions for use. https://www.agilent.com/cs/library/packageinsert/public/PD04163_rev_02_SK00521-5_IFU.pdf . Accessed 27 Mar 2024

Ahn S, Kim K-M (2021) PD-L1 expression in gastric cancer: interchangeability of 22C3 and 28–8 pharmDx assays for responses to immunotherapy. Mod Pathol 34:1719–1727. https://doi.org/10.1038/s41379-021-00823-9CrossRefPubMed

Bajorin DF, Witjes JA, Gschwend J, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat S, Park SH, Ye D, Agerbaek M, Collette S, Unsal-Kacmaz K, Zardavas D, Koon HB, Galsky MD (2021) First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC). J Clin Oncol 39:Abstract 391. https://doi.org/10.1200/JCO.2021.39.6_suppl.391CrossRef

Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD (2021) Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 384:2102–2114. https://doi.org/10.1056/NEJMoa2034442CrossRefPubMedPubMedCentral

Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Durán I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thåström A, Abidoye OO, Fine GD, Bajorin DF (2017) Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 389:67–76. https://doi.org/10.1016/s0140-6736(16)32455-2CrossRefPubMed

Baxi V, Lee G, Duan C, Pandya D, Cohen DN, Edwards R, Chang H, Li J, Elliott H, Pokkalla H, Glass B, Agrawal N, Lahiri A, Wang D, Khosla A, Wapinski I, Beck A, Montalto M (2022) Association of artificial intelligence-powered and manual quantification of programmed death-ligand 1 (PD-L1) expression with outcomes in patients treated with nivolumab & #xb1; ipilimumab. Mod Pathol 35:1529–1539. https://doi.org/10.1038/s41379-022-01119-2CrossRefPubMedPubMedCentral

Bera K, Schalper KA, Rimm DL, Velcheti V, Madabhushi A (2019) Artificial intelligence in digital pathology—new tools for diagnosis and precision oncology. Nat Rev Clin Oncol 16:703–715CrossRefPubMedPubMedCentral

Bristol Myers Squibb (2022) OPDIVO^® (nivolumab) [package insert]. https://packageinserts.bms.com/pi/pi_opdivo.pdf. Accessed 27 Mar 2024

10.

Bristol Myers Squibb (2022) Yervoy^®(ipilimumab) [package insert]. https://packageinserts.bms.com/pi/pi_yervoy.pdf. Accessed 27 Mar 2024

11.

Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, López-Ríos F, Penault-Llorca F, Viale G, Wotherspoon AC, Kerr KM, Tsao M-S (2017) Programmed death-ligand 1 immunohistochemistry testing: A review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 35:3867–3876. https://doi.org/10.1200/jco.2017.74.7642CrossRefPubMed

12.

CellCarta (2022) Pathotrainer: enabling pathology training and tuning in biomarker development. https://www.pathomation.com/pathotrainer-3/. Accessed 27 Mar 2024

13.

Chen L-T, Satoh T, Ryu M-H, Chao Y, Kato K, Chung HC, Chen J-S, Muro K, Kang WK, Yeh K-H, Yoshikawa T, Oh SC, Bai L-Y, Tamura T, Lee K-W, Hamamoto Y, Kim JG, Chin K, Oh D-Y, Minashi K, Cho JY, Tsuda M, Sameshima H, Kang Y-K, Boku N (2020) A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer 23:510–519. https://doi.org/10.1007/s10120-019-01034-7CrossRefPubMed

14.

Cserni B, Bori R, Csörgő E, Oláh-Németh O, Pancsa T, Sejben A, Sejben I, Vörös A, Zombori T, Nyári T, Cserni G (2022) ONEST (Observers Needed to Evaluate Subjective Tests) suggests four or more observers for a reliable assessment of the consistency of histological grading of invasive breast carcinoma: A reproducibility study with a retrospective view on previous studies. Pathol Res Pract 229:153718. https://doi.org/10.1016/j.prp.2021.153718CrossRefPubMed

15.

Downes MR, Slodkowska E, Katabi N, Jungbluth AA, Xu B (2020) Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma. Histopathology 76:191–200. https://doi.org/10.1111/his.13946CrossRefPubMed

16.

Eckstein M, Cimadamore A, Hartmann A, Lopez-Beltran A, Cheng L, Scarpelli M, Montironi R, Gevaert T (2019) PD-L1 assessment in urothelial carcinoma: a practical approach. Ann Transl Med 7:690. https://doi.org/10.21037/atm.2019.10.24CrossRefPubMedPubMedCentral

17.

Eckstein M, Erben P, Kriegmair MC, Worst TS, Weiß C-A, Wirtz RM, Wach S, Stoehr R, Sikic D, Geppert CI, Weyerer V, Bertz S, Breyer J, Otto W, Keck B, Burger M, Taubert H, Weichert W, Wullich B, Bolenz C, Hartmann A, Erlmeier F (2019) Performance of the Food and Drug Administration/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab. Eur J Cancer 106:234–243. https://doi.org/10.1016/j.ejca.2018.11.007CrossRefPubMed

18.

Eckstein M, Wirtz RM, Pfannstil C, Wach S, Stoehr R, Breyer J, Erlmeier F, Gunes C, Nitschke K, Weichert W, Otto W, Keck B, Eidt S, Burger M, Taubert H, Wullich B, Bolenz C, Hartmann A, Erben P (2018) A multicenter round robin test of PD-L1 expression assessment in urothelial bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis prediction after radical cystectomy. Oncotarget 9:15001–15014. https://doi.org/10.18632/oncotarget.24531CrossRefPubMedPubMedCentral

19.

Franklin C, Kader G, Mewborn D, Moreno J, Peck R, Perry M, Scheaffer R (2007) Guidelines for Assessment and Instruction in Statistics Education. https://web.archive.org/web/20130307004604/http:/www.amstat.org/education/gaise/GAISEPreK-12_Full.pdf. Accessed 27 Mar 2024

20.

Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical keynote-059 trial. JAMA Oncol 4:e180013. https://doi.org/10.1001/jamaoncol.2018.0013CrossRefPubMedPubMedCentral

21.

Genentech Inc (2022) TECENTRIQ^® (atezolizumab) [package insert]. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. Accessed 27 Mar 2024

22.

Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550. https://doi.org/10.1016/S0140-6736(15)01281-7CrossRefPubMed

23.

Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B, Mistry A, Kalamegham R, Averbuch S, Novotny J, Rubin E, Emancipator K, McCaffery I, Williams JA, Walker J, Longshore J, Tsao MS, Kerr KM (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12:208–222. https://doi.org/10.1016/j.jtho.2016.11.2228CrossRefPubMed

24.

Kim B, Lee C, Kim YA, Moon KC (2020) PD-L1 expression in muscle-invasive urinary bladder urothelial carcinoma according to basal/squamous-like phenotype. Front Oncol 10:527385. https://doi.org/10.3389/fonc.2020.527385CrossRefPubMedPubMedCentral

25.

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hogg D, Hill A, Marquez-Rodas I, Haanen J, Guidoboni M, Maio M, Schoffski P, Carlino MS, Lebbe C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bastholt L, Rizzo JI, Balogh A, Moshyk A, Hodi FS, Wolchok JD (2019) Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 381:1535–1546. https://doi.org/10.1056/NEJMoa1910836CrossRefPubMed

26.

Lawson NL, Dix CI, Scorer PW, Stubbs CJ, Wong E, Hutchinson L, McCall EJ, Schimpl M, DeVries E, Walker J, Williams GH, Hunt J, Barker C (2020) Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies. Mod Pathol 33:518–530. https://doi.org/10.1038/s41379-019-0372-zCrossRefPubMed

27.

Lopez-Beltran A, Cimadamore A, Blanca A, Massari F, Vau N, Scarpelli M, Cheng L, Montironi R (2021) Immune checkpoint inhibitors for the treatment of bladder cancer. Cancers (Basel) 13:131. https://doi.org/10.3390/cancers13010131CrossRefPubMedPubMedCentral

28.

Mansour MSI, Hejny K, Johansson F, Mufti J, Vidis A, Mager U, Dejmek A, Seidal T, Brunnström H (2021) Factors influencing concordance of PD-L1 expression between biopsies and cytological specimens in non-small cell lung cancer. Diagnostics (Basel) 11:1927. https://doi.org/10.3390/diagnostics11101927CrossRefPubMed

29.

Mok TSK, Wu Y-L, Kudaba I, Kowalski DM, Chul Cho B, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G, Investigators K- (2019) Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393:1819–1830. https://doi.org/10.1016/s0140-6736(18)32409-7CrossRefPubMed

30.

National Comprehensive Cancer Network (2022) NCCN Clinical practice guidelines in oncology. Bladder cancer. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf . Accessed 27 Mar 2024

31.

Prince EA, Sanzari JK, Pandya D, Huron D, Edwards R (2021) Analytical concordance of PD-L1 assays utilizing antibodies from FDA-approved diagnostics in advanced cancers: A systematic literature review. JCO Precis Oncol 5:953–973. https://doi.org/10.1200/PO.20.00412CrossRefPubMed

32.

Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL (2017) Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Mod Pathol 30:340–349. https://doi.org/10.1038/modpathol.2016.186CrossRefPubMed

33.

Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL (2020) Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Mod Pathol 33:1746–1752. https://doi.org/10.1038/s41379-020-0544-xCrossRefPubMedPubMedCentral

34.

Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II (2017) A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 3:1051–1058. https://doi.org/10.1001/jamaoncol.2017.0013CrossRefPubMedPubMedCentral

35.

Robert ME, Rüschoff J, Jasani B, Graham RP, Badve SS, Rodriguez-Justo M, Kodach LL, Srivastava A, Wang HL, Tang LH, Troncone G, Rojo F, Van Treeck BJ, Pratt J, Shnitsa I, Kumar G, Karasarides M, Anders RA (2023) High interobserver variability among pathologists using combined positive score to evaluate PD-L1 expression in gastric, gastroesophageal junction, and esophageal adenocarcinoma. Mod Pathol 36:100154. https://doi.org/10.1016/j.modpat.2023.100154CrossRefPubMed

36.

Scheel AH, Dietel M, Heukamp LC, Jöhrens K, Kirchner T, Reu S, Rüschoff J, Schildhaus H-U, Schirmacher P, Tiemann M, Warth A, Weichert W, Fischer RN, Wolf J, Buettner R (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29:1165–1172. https://doi.org/10.1038/modpathol.2016.117CrossRefPubMed

37.

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im S-A, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121. https://doi.org/10.1056/NEJMoa1809615CrossRefPubMed

38.

Schwamborn K, Ammann J, Knüchel R, Hartmann A, Baretton G, Lasitschka F, Schirmacher P, Braunschweig T, Tauber R, Erlmeier F, Hieke-Schulz S, Weichert W (2019) Multicentric analytical comparability study of programmed death-ligand 1 expression on tumor-infiltrating immune cells and tumor cells in urothelial bladder cancer using four clinically developed immunohistochemistry assays. Virchows Arch 475:599–608. https://doi.org/10.1007/s00428-019-02610-zCrossRefPubMedPubMedCentral

39.

Tsao MS, Kerr KM, Kockx M, Beasley MB, Borczuk AC, Botling J, Bubendorf L, Chirieac L, Chen G, Chou TY, Chung JH, Dacic S, Lantuejoul S, Mino-Kenudson M, Moreira AL, Nicholson AG, Noguchi M, Pelosi G, Poleri C, Russell PA, Sauter J, Thunnissen E, Wistuba I, Yu H, Wynes MW, Pintilie M, Yatabe Y, Hirsch FR (2018) PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project. J Thorac Oncol 13:1302–1311. https://doi.org/10.1016/j.jtho.2018.05.013CrossRefPubMedPubMedCentral

40.

Ventana Medical Systems Inc (2020) VENTANA PD-L1 (SP263) assay [package insert]. https://diagnostics.roche.com/ch/de/products/tests/ventana-pd-l1-_sp263-assay2.html. Accessed 27 Mar 2024

Titel: Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments
verfasst von: Josef Rüschoff
George Kumar
Sunil Badve
Bharat Jasani
Emma Krause
Nathalie Rioux-Leclercq
Federico Rojo
Maurizio Martini
Liang Cheng
Maria Tretiakova
Catherine Mitchell
Robert A. Anders
Marie E. Robert
Darren Fahy
Mike Pyle
Quang Le
Limin Yu
Benjamin Glass
Vipul Baxi
Zulfia Babadjanova
James Pratt
Sergine Brutus
Maria Karasarides
Arndt Hartmann
Publikationsdatum: 04.04.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-024-03795-8

Springer Medizin

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie