Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for Shifting Treatment Paradigms for Resectable Disease - PubMed (original) (raw)

Multicenter Study

. 2018 May;267(5):797-805.

doi: 10.1097/SLA.0000000000002574.

Alexandra G Lopez-Aguiar 1, Douglas J Anderson 2, Andrew B Adams 2, Ryan C Fields 3, Maria B Doyle 4, William C Chapman 4, Bradley A Krasnick 3, Sharon M Weber 5, Joshua D Mezrich 6, Ahmed Salem 5, Timothy M Pawlik 7, George Poultsides 8, Thuy B Tran 8, Kamran Idrees 9, Chelsea A Isom 9, Robert C G Martin 10, Charles R Scoggins 10, Perry Shen 11, Harveshp D Mogal 11, Carl Schmidt 12, Eliza Beal 12, Ioannis Hatzaras 13, Rivfka Shenoy 13, Kenneth Cardona 1, Shishir K Maithel 1

Affiliations

Multicenter Study

Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for Shifting Treatment Paradigms for Resectable Disease

Cecilia G Ethun et al. Ann Surg. 2018 May.

Abstract

Objective: To investigate the influence of type of surgery (transplant vs resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H-CCA).

Background: Outcomes after resection for H-CCA are poor, yet transplantation is currently only reserved for well-selected patients with unresectable disease.

Methods: All patients with H-CCA who underwent resection from 2000 to 2015 at 10 institutions were included. Three institutions additionally had active H-CCA transplant protocols with similar selection criteria over similar time periods.

Results: Of 304 patients with suspected H-CCA, 234 underwent attempted resection and 70 were enrolled in a transplant protocol. Excluding incomplete/R2 resections (n = 43), patients who were enrolled, but did not undergo transplant (n = 24), and transplants without confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent resection and 41 curative-intent transplant. Compared with resection, transplant patients were younger (52 vs 65 years; P < 0.001), and more frequently had primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise similar in demographics and comorbidities. Patients who underwent transplant for confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs 33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for tumors <3 cm with lymph-node negative disease, and excluding PSC patients, transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54% vs 29%; P = 0.03). Transplant remained associated with improved survival on intention-to-treat analysis, even after accounting for tumor size, lymph node status, and PSC (P = 0.049).

Conclusions: Resection for hilar cholangiocarcinoma that meets criteria for transplantation (<3 cm, lymph-node negative disease) is associated with substantially decreased survival compared to transplant for the same criteria with unresectable disease. Prospective trials are needed and justified.

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Figures

Figure 1

Figure 1

Flow diagram of patients with hilar cholangiocarcinoma included in the current study.

Figure 2

Figure 2

(A) Comparing all patients with pathologically-confirmed H-CCA who underwent curative-intent transplant (n=41) to those who underwent curative-intent resection (n=191). The median survival was not reached (MNR) among transplant patients, and 1-, 3-, and 5-year survivals were 93%, 72%, and 64%, respectively. The median survival among resection patients was 21.0 months (95% CI, 16.5–25.5), and 1-, 3-, and 5-year survivals were 71%, 33%, and 18%, respectively (log rank p<0.001). (B) Comparing all patients with pathologically-confirmed H-CCA who underwent curative-intent transplant to those who underwent curative-intent resection and had tumors <3cm in size and no lymph node disease (N0) on pathologic examination (n=57). The median survival for this subset of resection patients was 27.4 months (95% CI, 6.0–48.8), and 1-, 3-, and 5-year survivals were 72%, 45%, and 31%, respectively (log rank p<0.001).

Figure 3

Figure 3

(A) Comparing curative-intent transplantation for pathologically-confirmed H-CCA in non-PSC patients (n=16) to curative-intent resection in non-PSC patients with tumors <3cm and no lymph node disease (N0) on pathologic examination (n=56). The median survival was not reached (MNR) among non-PSC transplant patients, and 1-, 3-, and 5-year survivals were 94%, 54%, and 54%, respectively. The median survival for <3cm/N0 resection patients was 25.9 months (95% CI 13.0–38.7), and 1-, 3-, and 5-year survivals were 72%, 44%, and 29%, respectively (log rank p=0.03). (B)Comparing pathologically-confirmed, non-PSC transplant patients to non-PSC, <3cm/N0 resection patients who also had R0 resections (n=39). The median survival for this subset of resection patients was 28.3 months (95% CI 12.6–44.0), and 1-, 3-, and 5-year survivals were 75%, 49%, and 32%, respectively (log rank p=0.049).

Figure 4

Figure 4

Intention-to-treat analysis. (A)Comparing all patients enrolled in a transplant protocol (n=66) to all patients who underwent attempted resection with tumors <3cm and no lymph node disease (N0) on pathologic examination (n=58). Median overall survival among transplant patients was 77.4 months, and 1-, 3-, and 5-year survivals were 80%, 58%, and 53%, respectively. Median overall survival among resection patients was 27.4 months (95% CI, 5.5–49.3), and 1-, 3-, and 5-year survivals were 73%, 46%, 29%, respectively (log rank p=0.002). (B) Comparing all non-PSC patients enrolled in a transplant protocol (n=35) to all patients who underwent attempted resection with tumors <3cm and N0 disease on pathologic examination (n=57). Median overall survival among transplant patients was 32.5 months (95% CI, 13.5–51.5), and 1-, 3-, and 5-year survivals were 82%, 46%, and 41%, respectively. Median overall survival among resection patients was 27.4 months (95% CI, 6.0–48.8), and 1-, 3-, and 5-year survivals were 72%, 45%, and 27%, respectively (log rank p=0.049).

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References

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