IHPBA Top Abstracts

June/July 2022, Vol 3, No 2

The Cholangiocarcinoma (CCA) Summit “Live from the 2022 International Hepato-Pancreato-Biliary Association (IHPBA) World Congress” was shared with the CCA community on April 14, 2022. Dr Flavio Rocha, Chief of Surgical Oncology and Physician-in-Chief of the Knight Cancer Institute at Oregon Health & Science University, reviewed key abstracts on CCA and other biliary tract cancers presented at the IHPBA Congress.

Liver transplantation for unresectable perihilar cholangiocarcinoma. Is neoadjuvant chemoradiation therapy really necessary? An international, multicenter comparison (Abstract FP16-4)

The Mayo Clinic protocol is the standard to determine eligibility for liver transplantation and is based on strict selection criteria that include neoadjuvant chemoradiation before patients are eligible for liver transplantation. A multicenter retrospective study assessed whether survival outcomes associated with the Mayo Clinic protocol in patients with unresectable perihilar CCA were “truly due to the strict selection or due to the neoadjuvant chemoradiation.”

In this international study, 2 centers in the Netherlands and France reviewed charts of patients (n = 49) with unresectable perihilar CCA between 2011 and 2021 who were assessed with the Mayo Clinic selection criteria and stratified by neoadjuvant chemoradiation. The primary end point was overall survival (OS); secondary end points included post-transplant morbidity and vascular complications.

Of the 49 patients who underwent liver transplantation, 27 received chemoradiation and 22 did not; median age was 55 years. In the cohort that received neoadjuvant chemoradiation (median follow-up of 25 months), 1-year survival rate was 65%, 3-year survival rate was 51%, 5-year survival rate was 41%; the 1-year, 3-year, and 5-year survival rates of the cohort who had not received neoadjuvant chemoradiation were 91%, 68%, and 53%, respectively. The tumor 5-year recurrence rate was similar between the groups, 32% in the neoadjuvant chemoradiation cohort versus 53% in the non-chemoradiation cohort. However, major vascular complications (defined as Clavien-Dindo >IIIa) were significantly higher in the chemoradiation group (41% vs 14%).

In summary, Dr Rocha stated, “This was an interesting analysis that looked at survival after liver transplantation in a very highly selected patient cohort. They found that there was no difference in survival between patients who had received neoadjuvant chemoradiation and those who had not; however, there was an increased rate of vascular complications in those that did have chemoradiation.”

He noted that “The Mayo Clinic protocol has taken the test of time, and the chemoradiation piece does have significant treatment effect, with some folks even suggesting that the transplant is actually adjuvant therapy for chemoradiation. Although it is a hypothesis-generating approach, it is certainly food for thought, as we continue to evolve these transplant protocols on omitting chemoradiation.”

Neoadjuvant chemotherapy is associated with lower rates of margin-positive resection of intrahepatic cholangiocarcinoma (Abstract FP16-7)

Intrahepatic CCA (iCCA) is typically managed by upfront resection in suitable candidates. However, there is an interest in using neoadjuvant chemotherapy in order to reduce recurrence rates and improve outcomes. Dr Rebecca Marcus of the Providence Saint John’s Cancer Institute in the United States presented data on the role of neoadjuvant chemotherapy in patients with iCCA as predictors of treatment regimen and oncologic outcomes.

In this study, the investigators used a population-based National Cancer Database to identify patients with clinical stage I-III iCCA who underwent curative intent surgery between 2006 and 2016. These patients were then stratified in different cohorts: surgery alone, neoadjuvant therapy followed by surgery, or surgery with adjuvant therapy.

In the cohort of 2700 identified patients with resectable iCCA, the utilization of neoadjuvant therapy was low overall but increased over the study period (4.3% to 7.2% by the end of the study period). In terms of predictive factors, higher clinical stage was predictive of neoadjuvant therapy, while higher pathologic stage and positive resection margins were predictive of adjuvant therapy. Overall, the risk of death from iCCA decreased over the study period, which was attributed to improvements in surgical technique. In addition, neoadjuvant therapy was associated with a decrease in the incidence of margin-positive resection.

It was concluded that “utilization of neoadjuvant chemotherapy for the treatment of iCCA has certainly increased and the risk of death has decreased. Neoadjuvant therapy did decrease the incidence of margin-positive resections, which may have contributed to improved survival.” Dr Rocha noted, “What we do know is that prospective studies for neoadjuvant therapy are being conducted, and we hope that this will emerge as a new treatment strategy in the management of iCCA.”

Laparoscopic versus open liver section for gallbladder cancer and intrahepatic cholangiocarcinoma: the Mayo Clinic experience (Abstract FP10-5)

The safety and adequacy of laparoscopic liver surgery has not been well established in biliary tract cancers. An institutional retrospective matched cohort study identified patients in the Mayo Clinic’s institutional database who underwent laparoscopic versus open surgery and compared clinical operative and postoperative variables.

A total of 87 patients were identified, of which 33 underwent laparoscopic surgery and 54 underwent open resection. The patients who underwent laparoscopic resections had significantly lower blood loss, higher negative-margin resection rates, shorter length of stay, lower number of harvested lymph nodes, and were less likely to have major liver resection. There were no between-group differences in procedural time, tumor size, severe postoperative complications, need for adjuvant chemotherapy, or need for readmission.

It was concluded that “laparoscopic liver resections for GBC [gallbladder cancer] and iCCA are safe and appear to have at least some short-term benefits with appropriate patient selection and when these procedures are done by a high volume, experienced center. They also do not compromise any of the oncologic outcomes.”

Dr Rocha noted these results were hypothesis-generating. “I do think the shorter operative procedures can certainly help patients get onto adjuvant therapy quicker, which we know ultimately is what they need to control micrometastatic disease after surgery.”

Actual 10-year survival after resection of perihilar cholangiocarcinoma. What factors preclude cure? (Abstract FP10-2)

Long-term survival for patients with perihilar CCA (pCCA) is low, with a median OS of 19 to 39 months for patients undergoing curative-intent surgery.1 Dr Stefan Buettner from the Erasmus MC University Medical Center in the Netherlands presented results of a multi-institutional cohort study of patients with pCCA from Europe and the United States who underwent surgery between 2000 and 2009 in 22 centers across the 2 continents. The goal of the study was to determine the cure rate and to identify clinicopathologic factors that may preclude cure.

The patient cohort comprised 460 patients who underwent combined liver and biliary resection for histopathologically confirmed pCCA.1 Dr Rocha noted, “Although 10-year survival is rare for perihilar cholangiocarcinoma, we do like to use that period as perhaps the definition of a cure.”

With a median follow-up of 10 years, the median OS was 29.9 months and the 10-year OS was 12.8%.1 The observed cure rate was about 5%. Factors that precluded cure included age >70 years, more advanced tumors, patients who required hepatic artery reconstruction, and those who had positive resection margins.

In summary, Dr Rocha concluded that “10-year OS can be achieved even in patients with pCCA following resection. However, there are some adverse prognostic factors that should be considered when counseling patients and offering them such complex surgery.”

Intrahepatic cholangiocarcinoma: Does lymph node dissection affect survival? (Abstract FP06-7)

Dr Weeris Ouransatien from Thailand presented results of a retrospective study of 407 consecutive patients with iCCA who underwent surgery at the Sunpasitthiprasong Hospital over a 5-year period from 2013 to 2018. The role of lymph node dissection was investigated to determine if lymph node dissection would confer a survival benefit.

Of the 407 patients identified, 242 patients underwent curative intent resection, 173 patients had a lymph node dissection, and 69 patients had no lymph node dissection. The lymph node–positive ratio was about 50%. The median survival time was 14.6 in the lymph node dissection group. The lymph node–negative group had longer survival compared with the lymph node unsampled group. However, there was no difference in survival between the lymph node–positive group and the unsampled group. The authors concluded that “lymph node dissection appears to demonstrate true staging. If patients had lymph node negative disease, their OS was much better.”

Based on these results, Dr Rocha commented, “I think this is something that we see in many solid tumors where the physical removal of lymph nodes does not confer OS benefit. But if you don’t do the lymph node dissection, you may not know that the patients have lymph node positive disease. Given that adjuvant therapy is now given regardless of lymph node status, this may have less of an impact. However, most surgeons now, certainly in the US, do recommend a full lymph node dissection for iCCA.”

1300 consecutive surgeries for gallbladder cancer in the era of multimodality treatment: lessons learned and a way forward (Abstract FP06-2)

Dr Shraddha Patkar from the Tata Memorial Hospital in Mumbai, India, presented results of a retrospective study of 1307 patients who underwent surgeries for either preoperatively confirmed GBC or based on a radiographic suspicion of disease over a period of 10 years. Dr Rocha expressed, “I think it was very refreshing to see a paper coming from an endemic area like India, Chile, and Japan, where GBC is much more prevalent than US.”

Of the total population, almost 20% of patients had a benign diagnosis (n = 267). In the cohort of 1040 patients with GBC, at a median follow-up of 30 months, the 1-year OS rate was 81%, 3-year OS rate was 52%, and 5-year OS rate was 44%. Of these, 330 patients received neoadjuvant treatment and 566 patients received adjuvant treatment. Moreover, patients who had locally advanced disease but underwent curative surgery had an increased OS and disease-free survival compared with those who did not undergo surgery.

The authors concluded that “multimodality therapy is likely the way to move forward in GBC. While surgery certainly offers immediate benefit, we do know that patients recur and it’s hard to treat recurrent disease. It’s possible that neoadjuvant therapy may help select patients for surgery, but it is unclear whether it actually affects overall survival.”

Dr Rocha noted that “randomized trials are currently being done in this setting; in particular, one study is being conducted in the United States through the ECOG-ACRIN cooperative group [EA2197], which is looking at perioperative gemcitabine and cisplatin versus resection and adjuvant gemcitabine and cisplatin. And we hope to have those results in the next few years.”

Peritumoral microinvasion and risk of lymph node metastases for early gallbladder cancer (Abstract FP06-3)

Early GBC is often found incidentally, typically when patients have a cholecystectomy for gallstones or other benign conditions. Currently, radical resection is recommended for patients with T1b+ disease; however, other risk factors are poorly defined. Therefore, a study evaluated predictors for radical surgery in a cohort of Japanese patients who underwent resection for GBC; results of this study were presented by Dr Ito Hiromichi of the Japanese Foundation for Cancer Research.

A total of 79 patients who had pathologic T1 or T2 GBC following radical cholecystectomy were reviewed over a 14-year period. The study analyzed risk factors for nodal metastases, recurrence-free survival, and OS. Nodal metastases were found in 21 patients. Risk of nodal metastases was associated with tumor grade as well as lymphatic, venous, and perineural invasions. Of these, lymphatic and perineural invasion were found to be independent predictors of nodal metastasis in multivariate logistic regression analysis. Moreover, peritumoral lymphatic and neural invasion for early GBC were associated with the worst risk of lymph node metastases as well as poorest survival outcomes.

Based on these results, Dr Rocha expressed that “these results should be incorporated into decision-making for additional treatment for patients with incidental or early GBC. I would probably keep to the mantra of taking patients with a T1b pathology back to surgery for resection. I think the hard part is to determine whether T1a patients who may have some of these adverse features, would benefit from additional re-resection or potentially some preoperative therapy in terms of reducing their risk of recurrence.”

Summary

Overall, Dr Rocha concluded, “I think it’s really an exciting time for biliary tract cancers. As we have improved surgical techniques that have made liver surgery safer, we can now find systemic agents that work in this disease, particularly with the explosion of molecular profiling and genomics. We hope to study these new targets in randomized trials with the goal of improving outcome for patients.”

Reference

  1. Van Keulen A-M, Olthof PB, Cescon M, et al. Actual 10-year survival after resection of perihilar cholangiocarcinoma: what factors preclude a chance for cure? Cancers (Basel). 2021;13:6260.

Related Items

CCA Summit Live from IHPBA 2022
By Flavio G. Rocha, MD, FACS, FSSO
Videos
Flavio Rocha, MD, FACS, FSSO, the Hedinger Chair of Surgical Oncology and Physician-in-Chief of the Knight Cancer Institute at Oregon Health & Science University, presents an overview of the key abstracts on cholangiocarcinoma and gallbladder cancer presented at the 2022 annual meeting of IHPBA. Dr Rocha also provides his perspectives on the clinical impact of the data on patient outcomes.

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