- Email: [email protected]
AJCC consensus conference on staging of hepatocellular carcinoma: rationale and overview of the conference
HPB 2003 Volume 5, Number 4 238±242 DOI 10.1080/13651820310015824
AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: rationale and overview of the conference WS Helton1 and SM Strasberg2 1
Division of General Surgery, University of Illinois, Chicago, IL; and 2Section of Hepatobiliary-Pancreatic Surgery, Washington University in
Saint Louis, St Louis, MO, USA
The therapeutic approach to treating patients with hepatocellular carcinoma (HCC) has changed radically over the past few decades and continues to evolve as the biology and natural history of the disease become better understood and new effective treatment modalities are developed. Modern cancer therapy has evolved so that it can be speci®cally tailored in the best interests of an individual patient to avoid too much or too little therapy and to provide reasonably predictable outcomes and expectations. Such individualized therapy requires an accurate estimation of prognosis. Accurate prognostication, in turn, depends upon understanding the natural history of the disease for a given tumor stage, as well as the probability of survival in response to a speci®c therapy. Appropriate selection of individualized cancer therapy for patients with HCC is more complex than for most cancers because prognosis depends not just on the anatomic extent of the disease but also on liver function [1]. In fact, liver function is a more powerful predictor of survival as well as response to speci®c therapy than tumor stage for many patients with HCC. Staging systems incorporating some measure of liver function and/or hepatic reserve are expected to increase the power of discriminating patients with different prognosis as well as better predict tolerance and response to speci®c treatments [2]. The American Joint Commission on Cancer (AJCC) and International Union Against Cancer (UICC) also recognize that non-anatomic and patient factors can be powerful predictors of survival for some cancers [3, 4]. In fact, the most recent edition of the AJCC tumor-lymph node-metastasis (TNM) staging manual incorporated liver ®brosis as part of the TNM staging system as a means of improving prediction of survival for patients with HCC following tumor resection [5, 6]. The most widely used staging system for HCC currently in use is the UICC/AJCC TNM. This staging system describes the anatomic extent of cancer without
consideration of treatment and is based entirely upon survival statistics derived from patients undergoing surgical resection. Unfortunately, the majority of patients with HCC are not candidates for resection because of inadequate liver reserve. Hence, the AJCC staging system is of limited use for the majority of patients with HCC. In addition, the AJCC TNM staging system may not accurately predict survival for patients with HCC who undergo any number of treatments other than liver resection. For this reason, the TNM system as a means of supporting and improving clinical decision making is at risk of becoming obsolete [7]. Staging systems will change with advances in technology that lead to earlier diagnosis and new medical therapies that are found to be effective for speci®c stages of cancer. For example, percutaneous ethanol injection and radiofrequency ablation are effective at eradicating small (<3 cm) HCC, whereas liver transplantation and chemoembolization have been shown to improve survival for patients with more advanced stages of HCC [8]. Collectively, these four treatment modalities are more commonly used in the treatment of patients with HCC than is surgical resection. This fact is increasingly recognized by clinicians caring for patients with HCC and has led to dissatisfaction with staging systems based only upon surgical resection datasets and which do not incorporate some measure of liver function [9]. For this reason, a number of new staging systems have been developed over the past few years with the purpose of hopefully better selecting patients for speci®c therapies and more accurately predicting survival in response to new evolving technologies and therapies [2, 5, 10–12]. The united network for organ sharing (UNOS) also created a staging system for patients being listed for orthotopic liver transplantion in the USA with known HCC (http://www.unos.org/PoliciesandBylaws/policies/ docs/policy_8.doc). Individual transplant centers have
Correspondence to: WS Helton, Department of Surgery, University of Illinois at Chicago, Chicago, IL 60601, USA (e-mail: [email protected] or strasbergs@ msnotes.wustl.edu)
2003 Taylor & Francis
AHPBA/AJCC Concensus Conference on Staging of HCC
Table 1.
Programme of the conference
Staging of Hepatocellular Cancer: A Consensus Conference Boston MA, USA, November 1, 2002 Conference Chairperson: Scott Helton, MD, FACS, University of Illinois at Chicago, Chicago IL Consensus Panel Chairperson: Michael Henderson, MD, FACS, Cleveland Clinic, Cleveland OH Local Arrangements: Mark Callery, MD, FACS, Beth Israel Deaconess Medical Center, Boston MA Sponsors: American Hepato-Pancreato-Biliary Association (AHPBA) American Joint Commission on Cancer (AJCC) TissueLink Medical Inc. Beth Israel Deaconess Medical Center Program 0800-0815 Introduction and Welcome Steven M Strasberg, MD, President AHPBA, Washington University in Saint Louis, Saint Louis, MO Josef E Fischer, MD, Surgeon-in-Chief, Beth Israel Deaconess Medical Center, Boston MA 0815±08:30 Purpose of the Conference Scott Helton, MD, HCC Conference Chairperson, University of Illinois at Chicago, Chicago IL Each of the talks in this forum will be 30 minutes in length and will be followed by a 10 minute question period. Questions from the audience will be permitted after questions from the consensus panel. Introduction to Staging Moderator: Steven Strasberg, MD 8:30±9:10 The history and purpose of cancer staging systems Douglas Evans, MD, Leader GI Cancer Group, AJCC MD Anderson Cancer Center, Houston TX 9:10±9:50 Evaluation of the effectiveness of staging systems Irving Fleming, MD, University of Tennessee, Memphis, TN 9:50±10:00 Refreshment Break Hepatocellular Cancer as a Disease Moderator: Doug Hanto, MD 10:00±10:40 Epidemiology, Pathogenesis, and Clinical Presentation of HCC Adrian Di Bisceglie, MD, Saint Louis University, Saint Louis MO 10:40±11:20 Pathology of HCC Ian Wanless, MD, University of Toronto, Toronto, Canada 11:20±12:00 Treatment Overview of HCC CM Lo, MD, Center for Study of Liver Disease, University of Hong Kong Medical Center 12±1 pm Lunch Presentation of Staging Systems Moderator: Scott Helton, MD 1:00±1:40 American Joint Commission on Cancer (AJCC) System Nicholas Vauthey, MD, Anderson Cancer Center, Houston TX 1:40±2:20 Japanese Liver Tumor Study Group Staging System Masatoshi Makuuchi, MD, Tokyo University, Tokyo, Japan 2:20±3:00 Barcelona Clinic Liver Cancer (BCLC) Group Staging J Llovet, MD, BCLC Group, Liver Unit, Barcelona, Spain 3:00±3:10 Break 3:10±3:50 The Cancer of the Liver Italian Program (CLIP) Bruno Danielle, MD, Clinical Trials Unit, National Cancer Institute, Napoli, Italy 3:50±4:30 Chinese University Prognostic Index T WT Leung, MD, The Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong, SAR, China 4:30±5:00 Additional Question and Answers 5:00±5:10 Concluding Comments, Michael Henderson, MD, Chair, Cleveland Clinic, Cleveland OH 5:10±5:15 Welcome to Reception, Paul Levy, CEO, Beth Israel Deaconess Medical Center. 5:15±6:00 Reception
239
WS Helton and SM Strasberg
also published the results of their own staging systems based upon extended criteria of the UNOS system on the results of liver transplantation for HCC [13]. Unfortunately, the move towards using different staging systems for reporting the outcome of patients with HCC will defeat one of the most important goals and principles of cancer staging – the creation of a universally accepted dataset that will enable treatment results to be compared across institutions and regions as well as provide a basis for identifying effective new forms of treatment. The departure from using a universally acceptable staging system in favor of using country, institution, or association sponsored staging systems is a threat to our ability to learn more about the natural history of HCC, to interpret the medical literature, and to assess the ef®cacy of various new treatment options for HCC. The IHPBA executive council recognized this threat a couple of years ago and recommended the adoption of a universally acceptable staging system for HCC that all members of the IHPBA would be willing to use. A number of proposals were discussed at council but none were unanimously accepted. The issue was tabled. The AHBPA, recognizing the importance of the issues involved, offered to attempt to organize a consensus conference to resolve them. A secondary but important goal was the submission of manuscripts of high quality to HPB, a responsibility of each member of IHPBA council including the President of AHPBA. This proved to be challenging, since the IHPBA was unable to provide support for the conference. However, the AHPBA undertook to sponsor the conference and was able to ®nd excellent co-sponsors in the USA. The AJCC, in its mission to improve patient-centered cancer care, also recognizes the need to continually improve cancer staging, especially as advances in technology lead to earlier diagnosis and better response to therapy. For these reasons, the AHPBA and the AJCC jointly sponsored the consensus conference to discuss the problem of staging HCC. Additional sponsorship came from the Beth Israel Deaconess Medical Center, which provided the venue, and TissueLink Inc. (Dover, New Hampshire), which provided special travel funds. The conference was organized by W Scott Helton, MD, Chairperson, AHPBA Research and Education Committee 2001–2003 and Steven M Strasberg, MD, President, AHPBA, 2001–2003. It was held at the Beth Israel Deaconess Medical Center in Boston, MA, on 1
240
November 2002. The principal investigators of the ®ve most commonly employed HCC staging systems currently in use around the world were invited to present data and the rationale for their respective staging system to an international audience of 50 invited clinicians, all of whom are experts in the ®eld of hepatocellular carcioma, and to a consensus panel of seven experts in the ®elds of pathology, epidemiology, hepatology, liver surgery, and transplantation The consensus panel was chaired by Michael J Henderson, MD, ®rst president of the AHPBA. The consensus panel was given the speci®c task of identifying the best current staging system for HCC. There were four stated goals of the conference: 1) educate participants about the process and purpose of staging systems for cancer; 2) evaluate existing data and review current state of knowledge regarding natural history of HCC and its response to treatment as related to cancer stage; 3) identify the best current staging system for HCC; and 4) identify de®cits in HCC staging and come to some consensus as to how to improve future systems. The consensus conference was organized in two sessions (Table 1). The morning session was didactic and introduced the principles of staging and reviewed the natural history, pathology, and response to treatment of HCC with respect to tumor stage. Doug Evans, MD, leader of the gastrointestinal cancer group of AJCC, provided an overview on the history and purpose of cancer staging systems. Irving Fleming, MD, past president of the AJCC, gave an insightful talk on the evaluation of the effectiveness of staging systems and emphasized the importance of updating staging systems lest they become obsolete. Adrian Di Bisceglie, MD, St Louis University, provided an overview on the epidemiology, pathogenesis, and clinical presentation of HCC with an emphasis on how these factors differ around the world. Ian Wanless, MD, University of Toronto, provided a comprehensive update on the pathology of HCC and the importance of how microscopic, molecular, and immunohistochemical markers can predict survival. CM Lo, MD, University of Hong Kong Medical Center, presented a rational treatment overview of HCC based upon tumor stage. The afternoon session was devoted to the presentation of tumor staging systems. Nicholas Vauthey, MD Anderson Cancer Center, presented the recently revised and updated AJCC/TNM tumor staging system (6th edition, 2002). He reviewed why liver ®brosis was
AHPBA/AJCC Concensus Conference on Staging of HCC
incorporated into the staging system and presented data that demonstrates that degree of hepatic ®brosis predicts survival independent of T stage. Masatoshi Makuuchi, MD, of Tokyo University, presented a new version of the Japanese Liver Tumor Study Group Staging System. J Llovet, MD, of Barcelona, Spain, presented the Barcelona Clinic Liver (BCLC) Group Staging and made an argument for their system which is heavily weighted by performance status and liver disease score. He argued that their system can be used to appropriately select therapy for a given patient without knowing the true anatomic extent of disease. Bruno Danielle, MD, of the Clinical Trials Group, National Cancer Institute, Napoli, Italy, presented the the Cancer of the Liver Italian Program (CLIP). Dr TWT Leung, MD, of the Chinese University of Hong Kong presented the Chinese University Prognostic Index (CUPI). After each presentation throughout the day, the consensus panel members were allowed to ask the speakers questions about their data and the development of the staging system. Discussion was then opened to the audience and other speakers who were allowed to make comments or ask additional questions. The audience was an invited one and included many of the leading experts in this area from around the world including authorities from France (Belghiti, Cherqui), the UK (Benjamin, Garden), China (Lau), Spain (Bruix), Switzerland (Clavien), and the USA (Chapman, Choti, Clary, Hanto, Linehan, Pinson, Pitt). Their questions and comments were extremely important to the conference and undoubtedly in¯uenced the opinion of the consensus panel. Following the conference, the consensus panel convened on two separate occasions and reviewed the material presented at the conference. A consensus paper was drafted, circulated, and ®nally agreed upon, which is published in this journal. The panel was asked to consider the following issues while drafting the manuscript: 1) Given the attributes that characterize an ideal staging system and given the need for staging to guide clinical decision making in order to achieve the best patientspeci®c outcomes: what is the best current system for staging HCC?; 2) why is the system you selected the best?; 3) what are its strengths and weaknesses? And 4) what are the best attributes and failings of the other staging systems? In addition, the panel was asked for their recommendations for the future of staging HCC. Should non-anatomic prognostic factors be incorporated into
staging for HCC? If so, which ones and how best to incorporate them? What agencies or avenues are needed to achieve global resolution to adopt a uniform system? While the consensus paper that follows may not successfully answer all of the questions posed above, we believe that it does address many important issues for HCC staging. Given the myriad presentations and clinical courses of HCC, it may be that a single universal staging system is not practical for all patients. For example, a different staging system may be necessary for patients with cirrhosis and those without cirrhosis or for those undergoing surgical resection and those undergoing liver transplantation. Despite these issues or whatever staging system is applied, one thing is certain and that is the need to report the results of HCC treatment using a uniform staging system. An agreement to report using a standardized staging system will then greatly enhance our understanding of the natural history of HCC and its response to treatment.
References 1 Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular cancer and prognosis in relation to treatment. Study of 850 patients. Cancer 1985;56:918–28. 2 Llovet J, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classi®cation. Semin Liver Dis 1999;19:329–38. 3 Hermanek P, Sobin L, Wittekind C. How to improve the present TNM staging system. Cancer 1999;86:2189–91. 4 Yarbro J, Page D, Fielding L, et al. Communication from the American Joint Committee on Cancer. American Joint Comittee on Cancer Prognostic Factors Consensus Conference. Cancer 1999;86:2436–46. 5 Vauthey J, Lauwers G, Esnaola N, et al. Simpli®ed staging for hepatocellular carcinoma. J Clin Oncol 2002;20:1527– 36. 6 Greene F, Page D, Fleming I, et al. AJCC Cancer Staging Manual, 6th edn. Springer, 2002. 7 Fleming I. AJCC/TNM cancer staging, present and future. J Surg Oncol 2001;77:233–6. 8 Bruix J, Sherman M, Llovet J, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona2000 EASL Conference. J Hepatol 2001;35:421–30. 9 Bruix J, Llovet J. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35: 519–24. 10 Chevret S, Trinchet J, Mathieu D, et al. A new prognostic classi®cation for predicting survival in patients wtih hepatocellular carcinoma. J Hepatol 1999;31:133–41. 11 Japan, LCSGO. The General Rules for the Clinical and
241
WS Helton and SM Strasberg Pathological Study of Primary Liver Cancer, 4th edn. Tokyo: Kanehara & Co., 2000. 12 Leung T, Tang A, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program
242
staging system: a study based on 926 patients. Cancer 2002; 94:1760–9. 13 Yao F, Ferrell LD, Bass N, et al. Liver transplantation for hepatocellular carcinoma: expansion of tumor size limits does not adversely impact survival. Hepatology 2001; 33: 1394–403.
AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: rationale and overview of the conference WS Helton1 and SM Strasberg2 1
Division of General Surgery, University of Illinois, Chicago, IL; and 2Section of Hepatobiliary-Pancreatic Surgery, Washington University in
Saint Louis, St Louis, MO, USA
The therapeutic approach to treating patients with hepatocellular carcinoma (HCC) has changed radically over the past few decades and continues to evolve as the biology and natural history of the disease become better understood and new effective treatment modalities are developed. Modern cancer therapy has evolved so that it can be speci®cally tailored in the best interests of an individual patient to avoid too much or too little therapy and to provide reasonably predictable outcomes and expectations. Such individualized therapy requires an accurate estimation of prognosis. Accurate prognostication, in turn, depends upon understanding the natural history of the disease for a given tumor stage, as well as the probability of survival in response to a speci®c therapy. Appropriate selection of individualized cancer therapy for patients with HCC is more complex than for most cancers because prognosis depends not just on the anatomic extent of the disease but also on liver function [1]. In fact, liver function is a more powerful predictor of survival as well as response to speci®c therapy than tumor stage for many patients with HCC. Staging systems incorporating some measure of liver function and/or hepatic reserve are expected to increase the power of discriminating patients with different prognosis as well as better predict tolerance and response to speci®c treatments [2]. The American Joint Commission on Cancer (AJCC) and International Union Against Cancer (UICC) also recognize that non-anatomic and patient factors can be powerful predictors of survival for some cancers [3, 4]. In fact, the most recent edition of the AJCC tumor-lymph node-metastasis (TNM) staging manual incorporated liver ®brosis as part of the TNM staging system as a means of improving prediction of survival for patients with HCC following tumor resection [5, 6]. The most widely used staging system for HCC currently in use is the UICC/AJCC TNM. This staging system describes the anatomic extent of cancer without
consideration of treatment and is based entirely upon survival statistics derived from patients undergoing surgical resection. Unfortunately, the majority of patients with HCC are not candidates for resection because of inadequate liver reserve. Hence, the AJCC staging system is of limited use for the majority of patients with HCC. In addition, the AJCC TNM staging system may not accurately predict survival for patients with HCC who undergo any number of treatments other than liver resection. For this reason, the TNM system as a means of supporting and improving clinical decision making is at risk of becoming obsolete [7]. Staging systems will change with advances in technology that lead to earlier diagnosis and new medical therapies that are found to be effective for speci®c stages of cancer. For example, percutaneous ethanol injection and radiofrequency ablation are effective at eradicating small (<3 cm) HCC, whereas liver transplantation and chemoembolization have been shown to improve survival for patients with more advanced stages of HCC [8]. Collectively, these four treatment modalities are more commonly used in the treatment of patients with HCC than is surgical resection. This fact is increasingly recognized by clinicians caring for patients with HCC and has led to dissatisfaction with staging systems based only upon surgical resection datasets and which do not incorporate some measure of liver function [9]. For this reason, a number of new staging systems have been developed over the past few years with the purpose of hopefully better selecting patients for speci®c therapies and more accurately predicting survival in response to new evolving technologies and therapies [2, 5, 10–12]. The united network for organ sharing (UNOS) also created a staging system for patients being listed for orthotopic liver transplantion in the USA with known HCC (http://www.unos.org/PoliciesandBylaws/policies/ docs/policy_8.doc). Individual transplant centers have
Correspondence to: WS Helton, Department of Surgery, University of Illinois at Chicago, Chicago, IL 60601, USA (e-mail: [email protected] or strasbergs@ msnotes.wustl.edu)
2003 Taylor & Francis
AHPBA/AJCC Concensus Conference on Staging of HCC
Table 1.
Programme of the conference
Staging of Hepatocellular Cancer: A Consensus Conference Boston MA, USA, November 1, 2002 Conference Chairperson: Scott Helton, MD, FACS, University of Illinois at Chicago, Chicago IL Consensus Panel Chairperson: Michael Henderson, MD, FACS, Cleveland Clinic, Cleveland OH Local Arrangements: Mark Callery, MD, FACS, Beth Israel Deaconess Medical Center, Boston MA Sponsors: American Hepato-Pancreato-Biliary Association (AHPBA) American Joint Commission on Cancer (AJCC) TissueLink Medical Inc. Beth Israel Deaconess Medical Center Program 0800-0815 Introduction and Welcome Steven M Strasberg, MD, President AHPBA, Washington University in Saint Louis, Saint Louis, MO Josef E Fischer, MD, Surgeon-in-Chief, Beth Israel Deaconess Medical Center, Boston MA 0815±08:30 Purpose of the Conference Scott Helton, MD, HCC Conference Chairperson, University of Illinois at Chicago, Chicago IL Each of the talks in this forum will be 30 minutes in length and will be followed by a 10 minute question period. Questions from the audience will be permitted after questions from the consensus panel. Introduction to Staging Moderator: Steven Strasberg, MD 8:30±9:10 The history and purpose of cancer staging systems Douglas Evans, MD, Leader GI Cancer Group, AJCC MD Anderson Cancer Center, Houston TX 9:10±9:50 Evaluation of the effectiveness of staging systems Irving Fleming, MD, University of Tennessee, Memphis, TN 9:50±10:00 Refreshment Break Hepatocellular Cancer as a Disease Moderator: Doug Hanto, MD 10:00±10:40 Epidemiology, Pathogenesis, and Clinical Presentation of HCC Adrian Di Bisceglie, MD, Saint Louis University, Saint Louis MO 10:40±11:20 Pathology of HCC Ian Wanless, MD, University of Toronto, Toronto, Canada 11:20±12:00 Treatment Overview of HCC CM Lo, MD, Center for Study of Liver Disease, University of Hong Kong Medical Center 12±1 pm Lunch Presentation of Staging Systems Moderator: Scott Helton, MD 1:00±1:40 American Joint Commission on Cancer (AJCC) System Nicholas Vauthey, MD, Anderson Cancer Center, Houston TX 1:40±2:20 Japanese Liver Tumor Study Group Staging System Masatoshi Makuuchi, MD, Tokyo University, Tokyo, Japan 2:20±3:00 Barcelona Clinic Liver Cancer (BCLC) Group Staging J Llovet, MD, BCLC Group, Liver Unit, Barcelona, Spain 3:00±3:10 Break 3:10±3:50 The Cancer of the Liver Italian Program (CLIP) Bruno Danielle, MD, Clinical Trials Unit, National Cancer Institute, Napoli, Italy 3:50±4:30 Chinese University Prognostic Index T WT Leung, MD, The Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong, SAR, China 4:30±5:00 Additional Question and Answers 5:00±5:10 Concluding Comments, Michael Henderson, MD, Chair, Cleveland Clinic, Cleveland OH 5:10±5:15 Welcome to Reception, Paul Levy, CEO, Beth Israel Deaconess Medical Center. 5:15±6:00 Reception
239
WS Helton and SM Strasberg
also published the results of their own staging systems based upon extended criteria of the UNOS system on the results of liver transplantation for HCC [13]. Unfortunately, the move towards using different staging systems for reporting the outcome of patients with HCC will defeat one of the most important goals and principles of cancer staging – the creation of a universally accepted dataset that will enable treatment results to be compared across institutions and regions as well as provide a basis for identifying effective new forms of treatment. The departure from using a universally acceptable staging system in favor of using country, institution, or association sponsored staging systems is a threat to our ability to learn more about the natural history of HCC, to interpret the medical literature, and to assess the ef®cacy of various new treatment options for HCC. The IHPBA executive council recognized this threat a couple of years ago and recommended the adoption of a universally acceptable staging system for HCC that all members of the IHPBA would be willing to use. A number of proposals were discussed at council but none were unanimously accepted. The issue was tabled. The AHBPA, recognizing the importance of the issues involved, offered to attempt to organize a consensus conference to resolve them. A secondary but important goal was the submission of manuscripts of high quality to HPB, a responsibility of each member of IHPBA council including the President of AHPBA. This proved to be challenging, since the IHPBA was unable to provide support for the conference. However, the AHPBA undertook to sponsor the conference and was able to ®nd excellent co-sponsors in the USA. The AJCC, in its mission to improve patient-centered cancer care, also recognizes the need to continually improve cancer staging, especially as advances in technology lead to earlier diagnosis and better response to therapy. For these reasons, the AHPBA and the AJCC jointly sponsored the consensus conference to discuss the problem of staging HCC. Additional sponsorship came from the Beth Israel Deaconess Medical Center, which provided the venue, and TissueLink Inc. (Dover, New Hampshire), which provided special travel funds. The conference was organized by W Scott Helton, MD, Chairperson, AHPBA Research and Education Committee 2001–2003 and Steven M Strasberg, MD, President, AHPBA, 2001–2003. It was held at the Beth Israel Deaconess Medical Center in Boston, MA, on 1
240
November 2002. The principal investigators of the ®ve most commonly employed HCC staging systems currently in use around the world were invited to present data and the rationale for their respective staging system to an international audience of 50 invited clinicians, all of whom are experts in the ®eld of hepatocellular carcioma, and to a consensus panel of seven experts in the ®elds of pathology, epidemiology, hepatology, liver surgery, and transplantation The consensus panel was chaired by Michael J Henderson, MD, ®rst president of the AHPBA. The consensus panel was given the speci®c task of identifying the best current staging system for HCC. There were four stated goals of the conference: 1) educate participants about the process and purpose of staging systems for cancer; 2) evaluate existing data and review current state of knowledge regarding natural history of HCC and its response to treatment as related to cancer stage; 3) identify the best current staging system for HCC; and 4) identify de®cits in HCC staging and come to some consensus as to how to improve future systems. The consensus conference was organized in two sessions (Table 1). The morning session was didactic and introduced the principles of staging and reviewed the natural history, pathology, and response to treatment of HCC with respect to tumor stage. Doug Evans, MD, leader of the gastrointestinal cancer group of AJCC, provided an overview on the history and purpose of cancer staging systems. Irving Fleming, MD, past president of the AJCC, gave an insightful talk on the evaluation of the effectiveness of staging systems and emphasized the importance of updating staging systems lest they become obsolete. Adrian Di Bisceglie, MD, St Louis University, provided an overview on the epidemiology, pathogenesis, and clinical presentation of HCC with an emphasis on how these factors differ around the world. Ian Wanless, MD, University of Toronto, provided a comprehensive update on the pathology of HCC and the importance of how microscopic, molecular, and immunohistochemical markers can predict survival. CM Lo, MD, University of Hong Kong Medical Center, presented a rational treatment overview of HCC based upon tumor stage. The afternoon session was devoted to the presentation of tumor staging systems. Nicholas Vauthey, MD Anderson Cancer Center, presented the recently revised and updated AJCC/TNM tumor staging system (6th edition, 2002). He reviewed why liver ®brosis was
AHPBA/AJCC Concensus Conference on Staging of HCC
incorporated into the staging system and presented data that demonstrates that degree of hepatic ®brosis predicts survival independent of T stage. Masatoshi Makuuchi, MD, of Tokyo University, presented a new version of the Japanese Liver Tumor Study Group Staging System. J Llovet, MD, of Barcelona, Spain, presented the Barcelona Clinic Liver (BCLC) Group Staging and made an argument for their system which is heavily weighted by performance status and liver disease score. He argued that their system can be used to appropriately select therapy for a given patient without knowing the true anatomic extent of disease. Bruno Danielle, MD, of the Clinical Trials Group, National Cancer Institute, Napoli, Italy, presented the the Cancer of the Liver Italian Program (CLIP). Dr TWT Leung, MD, of the Chinese University of Hong Kong presented the Chinese University Prognostic Index (CUPI). After each presentation throughout the day, the consensus panel members were allowed to ask the speakers questions about their data and the development of the staging system. Discussion was then opened to the audience and other speakers who were allowed to make comments or ask additional questions. The audience was an invited one and included many of the leading experts in this area from around the world including authorities from France (Belghiti, Cherqui), the UK (Benjamin, Garden), China (Lau), Spain (Bruix), Switzerland (Clavien), and the USA (Chapman, Choti, Clary, Hanto, Linehan, Pinson, Pitt). Their questions and comments were extremely important to the conference and undoubtedly in¯uenced the opinion of the consensus panel. Following the conference, the consensus panel convened on two separate occasions and reviewed the material presented at the conference. A consensus paper was drafted, circulated, and ®nally agreed upon, which is published in this journal. The panel was asked to consider the following issues while drafting the manuscript: 1) Given the attributes that characterize an ideal staging system and given the need for staging to guide clinical decision making in order to achieve the best patientspeci®c outcomes: what is the best current system for staging HCC?; 2) why is the system you selected the best?; 3) what are its strengths and weaknesses? And 4) what are the best attributes and failings of the other staging systems? In addition, the panel was asked for their recommendations for the future of staging HCC. Should non-anatomic prognostic factors be incorporated into
staging for HCC? If so, which ones and how best to incorporate them? What agencies or avenues are needed to achieve global resolution to adopt a uniform system? While the consensus paper that follows may not successfully answer all of the questions posed above, we believe that it does address many important issues for HCC staging. Given the myriad presentations and clinical courses of HCC, it may be that a single universal staging system is not practical for all patients. For example, a different staging system may be necessary for patients with cirrhosis and those without cirrhosis or for those undergoing surgical resection and those undergoing liver transplantation. Despite these issues or whatever staging system is applied, one thing is certain and that is the need to report the results of HCC treatment using a uniform staging system. An agreement to report using a standardized staging system will then greatly enhance our understanding of the natural history of HCC and its response to treatment.
References 1 Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular cancer and prognosis in relation to treatment. Study of 850 patients. Cancer 1985;56:918–28. 2 Llovet J, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classi®cation. Semin Liver Dis 1999;19:329–38. 3 Hermanek P, Sobin L, Wittekind C. How to improve the present TNM staging system. Cancer 1999;86:2189–91. 4 Yarbro J, Page D, Fielding L, et al. Communication from the American Joint Committee on Cancer. American Joint Comittee on Cancer Prognostic Factors Consensus Conference. Cancer 1999;86:2436–46. 5 Vauthey J, Lauwers G, Esnaola N, et al. Simpli®ed staging for hepatocellular carcinoma. J Clin Oncol 2002;20:1527– 36. 6 Greene F, Page D, Fleming I, et al. AJCC Cancer Staging Manual, 6th edn. Springer, 2002. 7 Fleming I. AJCC/TNM cancer staging, present and future. J Surg Oncol 2001;77:233–6. 8 Bruix J, Sherman M, Llovet J, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona2000 EASL Conference. J Hepatol 2001;35:421–30. 9 Bruix J, Llovet J. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35: 519–24. 10 Chevret S, Trinchet J, Mathieu D, et al. A new prognostic classi®cation for predicting survival in patients wtih hepatocellular carcinoma. J Hepatol 1999;31:133–41. 11 Japan, LCSGO. The General Rules for the Clinical and
241
WS Helton and SM Strasberg Pathological Study of Primary Liver Cancer, 4th edn. Tokyo: Kanehara & Co., 2000. 12 Leung T, Tang A, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program
242
staging system: a study based on 926 patients. Cancer 2002; 94:1760–9. 13 Yao F, Ferrell LD, Bass N, et al. Liver transplantation for hepatocellular carcinoma: expansion of tumor size limits does not adversely impact survival. Hepatology 2001; 33: 1394–403.