Introduction: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assessment is mandatory for the single agent pembrolizumab treatment of patients with advanced non-small cell lung cancer (NSCLC). PD-L1 testing has been validated and is currently certified only on formalin-fixed paraffin-embedded materials but not on cytological smears. Unfortunately, a significant proportion of patients, having only cytological material available, cannot be tested for PD-L1 and treated with pembrolizumab. In this study, we aimed to validate PD-L1 IHC on cytological smears prospectively by comparing clone SP263 staining in 150 paired histological samples and cytological smears of NSCLC patients. Methods: We prospectively enrolled 150 consecutive advanced NSCLC patients. The clone SP263 was selected as, in a previous study of our group, it showed higher accuracy compared with clones 28-8 and 22-C3, with good cyto-histological agreement using a cut-off of 50%. For cyto-histological concordance, we calculated the kappa coefficient using two different cut-offs according to the percentage of PD-L1 positive neoplastic cells (<1%, 1–49% and ⩾50%; <50%, ⩾50%). Results: The overall agreement between histological samples and cytological smears was moderate (kappa = 0.537). However, when the cyto-histological concordance was calculated using the cut-off of 50%, the agreement was good (kappa = 0.740). With the same cut-off, and assuming as gold-standard the results on formalin-fixed paraffin-embedded materials, PD-L1 evaluation on smears showed specificity and negative predictive values of 98.1% and 93.9%, respectively. Conclusion: Cytological smears can be used in routine clinical practice for PD-L1 assessment with a cut-off of 50%, expanding the potential pool of NSCLC patients as candidates for first-line single agent pembrolizumab therapy.

Reliability of programmed death ligand 1 (PD-L1) tumor proportion score (TPS) on cytological smears in advanced non-small cell lung cancer: a prospective validation study

Ricci C.;Capizzi E.;Giunchi F.;Casolari L.;Gelsomino F.;Rihawi K.;Livi V.;Fiorentino M.;Ardizzoni A.
2020

Abstract

Introduction: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assessment is mandatory for the single agent pembrolizumab treatment of patients with advanced non-small cell lung cancer (NSCLC). PD-L1 testing has been validated and is currently certified only on formalin-fixed paraffin-embedded materials but not on cytological smears. Unfortunately, a significant proportion of patients, having only cytological material available, cannot be tested for PD-L1 and treated with pembrolizumab. In this study, we aimed to validate PD-L1 IHC on cytological smears prospectively by comparing clone SP263 staining in 150 paired histological samples and cytological smears of NSCLC patients. Methods: We prospectively enrolled 150 consecutive advanced NSCLC patients. The clone SP263 was selected as, in a previous study of our group, it showed higher accuracy compared with clones 28-8 and 22-C3, with good cyto-histological agreement using a cut-off of 50%. For cyto-histological concordance, we calculated the kappa coefficient using two different cut-offs according to the percentage of PD-L1 positive neoplastic cells (<1%, 1–49% and ⩾50%; <50%, ⩾50%). Results: The overall agreement between histological samples and cytological smears was moderate (kappa = 0.537). However, when the cyto-histological concordance was calculated using the cut-off of 50%, the agreement was good (kappa = 0.740). With the same cut-off, and assuming as gold-standard the results on formalin-fixed paraffin-embedded materials, PD-L1 evaluation on smears showed specificity and negative predictive values of 98.1% and 93.9%, respectively. Conclusion: Cytological smears can be used in routine clinical practice for PD-L1 assessment with a cut-off of 50%, expanding the potential pool of NSCLC patients as candidates for first-line single agent pembrolizumab therapy.
Ricci C.; Capizzi E.; Giunchi F.; Casolari L.; Gelsomino F.; Rihawi K.; Natali F.; Livi V.; Trisolini R.; Fiorentino M.; Ardizzoni A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/790651
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