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. 2022 Sep 30:9:893252.
doi: 10.3389/fmed.2022.893252. eCollection 2022.

Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand

Chaiwat Aphivatanasiri  1   2   3 , Prakasit Sa-Ngiamwibool  1   2   3 , Sakkarn Sangkhamanon  1   2   3 , Piyapharom Intarawichian  1   2   3 , Waritta Kunprom  1   2   3 , Malinee Thanee  1   2   3 , Piya Prajumwongs  1   2   3 , Narong Khuntikeo  1   2   4 , Attapol Titapun  1   2   4 , Apiwat Jareanrat  1   2   4 , Vasin Thanasukarn  1   2   4 , Tharatip Srisuk  1   2   4 , Vor Luvira  1   2   4 , Kulyada Eurboonyanun  1   2   5 , Julaluck Promsorn  1   2   5 , Watcharin Loilome  1   2   6 , Aileen Wee  7 , Supinda Koonmee  1   2   3
Affiliations

Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand

Chaiwat Aphivatanasiri et al. Front Med (Lausanne). .

Abstract

Aim: This study aims to improve the classification performance of the eighth American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) by proposing the Khon Kaen University (KKU) staging system developed in cholangiocarcinoma-prevalent Northeast Thailand.

Method: Four hundred eighty-eight patients with pCCA who underwent partial hepatectomy between 2002 and 2017 at the Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were included. Overall survival (OS) related to clinicopathological features was analyzed using the Kaplan-Meier method. Logrank test was performed in univariate analysis to compare OS data of clinicopathological features to determine risk factors for poor survival. Significant features were further analyzed by multivariate analysis (Cox regression) to identify prognostic factors which were then employed to modify the eighth AJCC staging system.

Results: Multivariate analysis showed that growth pattern (HR = 4.67-19.72, p < 0.001), moderately and poorly differentiated histological grades (HR = 2.31-4.99, p < 0.05 and 0.001, respectively), lymph node metastasis N1 and N2 (HR = 1.37 and 2.18, p < 0.05 and 0.01, respectively), and distant metastasis (HR = 2.11, p < 0.001) were independent factors when compared to their respective reference groups. There was a clear separation of patients with pCCA into KKU stage: I [OS = 116 months (mo.)], II (OS = 46 mo.), IIIA (OS = 24 mo.), IIIB (11 mo.), IVA (OS = 7 mo.), and IVB (OS = 6 mo.).

Conclusion: The new staging system was based on the incorporation of growth patterns to modify the eighth AJCC staging system. The classification performance demonstrated that the KKU staging system was able to classify and distinctly separate patients with pCCA into those with good and poor outcomes. It was also able to improve the stratification performance and discriminative ability of different stages of pCCA classification better than the eighth AJCC staging system. Hence, the KKU staging system is proposed as an alternative model to augment the accuracy of survival prognostication and treatment performance for patients with pCCA.

Keywords: KKU staging system; classification; eighth AJCC/UICC staging; growth pattern; perihilar cholangiocarcinoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic design for this study on the modification of the eighth edition AJCC/UICC staging system to the Khon Kaen University (KKU) staging system for the prognostic stratification and management of patients with perihilar cholangiocarcinoma in Northeast Thailand.
Figure 2
Figure 2
Correlation of overall survival of patients with perihilar cholangiocarcinoma with clinicopathological features. Correlation of OS with (A) age, (B) gender, (C) tumor size, (D) growth patterns, (E) surgical margin, (F) histological type, (G) histological grade, (H) T stage, (I) lymph node metastasis, and (J) distant metastasis.
Figure 3
Figure 3
Kaplan–Meier curve represented the overall survival of patients with perihilar cholangiocarcinoma with TNM stages by the eighth AJCC staging system. The table represented the outcomes of patients with TNM stage by the eighth AJCC staging system, namely, TNM stage, number of cases, overall survival, 5-year survival rate, hazard ratio, and p-value.
Figure 4
Figure 4
Growth patterns of perihilar cholangiocarcinoma. Non-invasive intraductal (ID), invasive ID, periductal infiltrating (PI), mass-forming (MF), and mixed types comprising ID+PI, ID+MF, PI+MF, and ID+PI+MF. Yellow, white, and red arrows indicate ID, PI, and MF, respectively.
Figure 5
Figure 5
Kaplan–Meier curve represented the overall survival of subgroup coordinating growth pattern and lymph node status (N0 and N1) in patients with perihilar cholangiocarcinoma. The table represented the outcomes of subgroup analysis, namely, subgroups of growth patterns, number of cases, overall survival, 5-year survival rate, hazard ratio, and p-value. **p < 0.01, ***p < 0.001, and ns = no statistical significance.
Figure 6
Figure 6
Kaplan–Meier curve represented the overall survival of the G category in the KKU staging system for classifying patients with perihilar cholangiocarcinoma. The table represented the outcomes of patients with G category classification, namely, groups, number of cases, overall survival, 5-year survival rate, hazard ratio, and p-value. ***p < 0.001.
Figure 7
Figure 7
Kaplan–Meier curve represented the overall survival of perihilar cholangiocarcinoma patients with GNM stages by the KKU staging system. The table represented the outcomes of patients with GNM stage by the KKU staging system, namely, KKU stage, number of cases, overall survival, 5-year survival rate, hazard ratio, and p-value. **p < 0.01 and ***p < 0.001.
Figure 8
Figure 8
Schematic of the KKU staging system for classifying patients with perihilar cholangiocarcinoma.
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