Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1)

Abstract

Background Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists. This study aimed to investigate whether gastrointestinal/pancreatic pathologists can reliably identify treatment effect on tumour by histology, and to determine the interobserver agreement for current tumour response scoring systems. Methods Overall, 23 gastrointestinal/pancreatic pathologists reviewed digital haematoxylin and eosin-stained slides of pancreatic cancer or treated tumour bed. The accuracy in identifying the treatment effect was investigated in 60 patients (30 treatment-naive, 30 after neoadjuvant therapy (NAT)). The interobserver agreement for the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDACC) tumour response scoring systems was assessed in 50 patients using intraclass correlation coefficients (ICCs). An ICC value below 0.50 indicated poor reliability, 0.50 or more and less than 0.75 indicated moderate reliability, 0.75 or more and below 0.90 indicated good reliability, and above 0.90 indicated excellent reliability. Results The sensitivity and specificity for identifying NAT effect were 76.2 and 49.0 per cent respectively. After NAT in 50 patients, ICC values for both tumour response scoring systems were moderate: 0.66 for CAP and 0.71 for MDACC. Conclusion Identification of the effect of NAT in resected pancreatic cancer proved unreliable, and interobserver agreement for the current tumour response scoring systems was suboptimal. These findings support the recently published International Study Group of Pancreatic Pathologists recommendations to score residual tumour burden rather than tumour regression after NAT.

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

“…Although gut microbial signatures of PDAC in human patients have recently been reported [ 49 ], associations between PDAC treatment response and the composition of the gut microbiome have largely been limited to animal studies. There are multiple methods by which the progress of PDAC can be monitored in patients, such as carbohydrate antigen 19-9 (Ca19-9) levels, radiological tumour response or pathological tumour regression grading [ 104 , 105 ]. As such, future prospective studies should seek to correlate the response to systemic treatment with the composition of the gut microbiome.…”

Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis

“…Consequently, the variable effect of neoadjuvant treatment within the individual tumour is intimately connected with pathology-based margin assessment and patient outcomes. Notably, assessment of tumour regression itself is highly observer-dependent 55 .…”

Identification of tumour regression in neoadjuvantly treated pancreatic cancer is based on divergent and nonspecific criteria

“…7,8 Not surprisingly, interobserver agreement for the most widely used TR-grading systems, recommended by the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDA), 9,10 is not satisfactory, which has been ascribed to the subjective nature of the defining criteria of the categories in both systems. 8,11 In this study, we hypothesized that a further important cause for interobserver variation in TR-grading of PDAC is a divergence in opinion regarding the morphological features of TR. To this end, tissue areas considered showing TR by three experienced pancreatic pathologists were compared.…”