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Conventional adverse features do not predict response to adjuvant chemotherapy in stage II colon cancer Sze-Lin Peng,* Michelle Thomas,* Andrew Ruszkiewicz,† Andrew Hunter,* Matthew Lawrence* and James Moore* *Colorectal Surgery Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia and †Department of Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Key words adjuvant chemotherapy, risk factor, stage II colon cancer, survival rate, treatment outcome. Correspondence Dr Sze-Lin Peng, Middlemore Hospital, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand. Email: [email protected] S.-L. Peng MBChB, FRACS; M. Thomas PhD, FRACS; A. Ruszkiewicz MD, FRCPA; A. Hunter MBBS, FRACS; M. Lawrence MBBS, FRACS; J. Moore MD, FRACS. Details of this paper have been presented in oral presentations at the ASC Adelaide 2011 and the American Society of Colon and Rectal Surgery 2012. The paper was awarded the Mark Killingback Prize in 2011. Accepted for publication 7 October 2013. doi: 10.1111/ans.12444
Abstract Background: The role of adjuvant chemotherapy in patients with stage II colon cancer is unclear. Current guidelines recommend adjuvant chemotherapy for high-risk patients, although the benefit demonstrated to date is small. Our study examined if adjuvant chemotherapy is associated with improved cancer-specific survival in highrisk patients with stage II colon cancer. Methods: A retrospective review was performed on patients with stage II (T34N0M0) colon cancer in a multi-institutional database from 1999 to 2007. Additionally, histology slides were reviewed and cancer-specific survival data were obtained from the state cancer registry. Adverse features examined were perforation, obstruction, T4 disease, poor differentiation, nodal yield less than 12, lymphovascular invasion and perineural invasion. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Results: There were 458 patients in the study, with a median follow-up of 5.2 years. Four patients (0.8%) were lost to follow-up. There were 290 (63%) high-risk patients, defined as having at least one adverse feature. Patients who had adjuvant chemotherapy were significantly younger (median 61 years versus 72 years, P < 0.001) but had comparable ASA score (median 2 versus 2, P = 0.3). There was no significant survival benefit observed associated with any one factor or when grouped. In high-risk patients the 5-year cancer specific survival with adjuvant chemotherapy was 84.8% (95% CI 78.7–91.9) compared to surgery alone 92.7% (95% CI 88.5–96.1), P = 0.85). Conclusion: Adjuvant chemotherapy did not significantly improve cancer-specific survival in patients with stage II colon cancer with adverse features. Other markers for selecting appropriate patients for adjuvant treatment are required.
Introduction There is controversy surrounding the role of adjuvant chemotherapy in stage II colon cancer. Stage II colon cancer accounts for up to one-third of colorectal cancer (CRC) and the majority of affected patients have an excellent predicted 5-year survival of around 80%.1,2 However, around 10–30% of stage II patients have poorer survival associated with the presence of adverse features, such as advanced T stage, poor differentiation, tumour perforation and lymphovascular invasion (LVI).3–6 For this reason, current guidelines recommend that patients with high-risk features, especially young patients, be considered for © 2013 Royal Australasian College of Surgeons
adjuvant treatment.7–9 Adjuvant chemotherapy has only been shown to confer a 3–5% improvement in survival in patients with stage II colon cancer.7,10 Therefore, the small relative benefit of treatment should be considered against the significant increase in resources required to manage this group. The aim of this study was to review our own data to determine if poor prognostic factors predicted a survival benefit from adjuvant chemotherapy given for stage II colon cancer. We also examined factors that influence the decision to offer adjuvant chemotherapy in this setting. We hypothesized that while large studies with heterogeneous patients showed a small benefit with adjuvant chemotherapy, in clinical practice, no benefit would be realized. ANZ J Surg 84 (2014) 837–841
838
Methods A retrospective review of patients with CRC was conducted on the Northern Adelaide Colorectal Unit (NACU) database. The NACU comprises three public teaching hospitals in Adelaide and the database has been prospectively maintained from 1999 to 2007. In addition to patient demographic data, date of surgery, surgical details including operation performed and post-operative complications, pathology data including tumour site, TNM stage and grade are collected. American Society of Anaesthesiologists (ASA) score is also collected as a measure of patient co-morbidity. Patients were staged as stage I (T1-2N0M0), stage II (T3-4N0M0), stage III (any T,N1-2-M0) or stage IV (M1 metastatic), according to the AJCC TNM11 system. For the purposes of this study, patients were eligible for inclusion if they underwent resection for a histologically proven T3 or T4 node negative adenocarcinoma of the colon (defined as being above 15 cm from the anal verge). Patients with rectal cancer (defined as less than or equal to 15 cm from the anal verge) were excluded due to the potential confounding factor of neoadjuvant chemoradiation therapy. Patients with non-adenocarcinoma tumours, distant disease (M1) or residual local disease after resection (R1 or R2 resection) and either metachronous tumours within 5 years or synchronous tumours of a more advanced stage were excluded. Nodal micrometastasis (defined as isolated tumour cells
Conventional adverse features do not predict response to adjuvant chemotherapy in stage II colon cancer Sze-Lin Peng,* Michelle Thomas,* Andrew Ruszkiewicz,† Andrew Hunter,* Matthew Lawrence* and James Moore* *Colorectal Surgery Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia and †Department of Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Key words adjuvant chemotherapy, risk factor, stage II colon cancer, survival rate, treatment outcome. Correspondence Dr Sze-Lin Peng, Middlemore Hospital, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand. Email: [email protected] S.-L. Peng MBChB, FRACS; M. Thomas PhD, FRACS; A. Ruszkiewicz MD, FRCPA; A. Hunter MBBS, FRACS; M. Lawrence MBBS, FRACS; J. Moore MD, FRACS. Details of this paper have been presented in oral presentations at the ASC Adelaide 2011 and the American Society of Colon and Rectal Surgery 2012. The paper was awarded the Mark Killingback Prize in 2011. Accepted for publication 7 October 2013. doi: 10.1111/ans.12444
Abstract Background: The role of adjuvant chemotherapy in patients with stage II colon cancer is unclear. Current guidelines recommend adjuvant chemotherapy for high-risk patients, although the benefit demonstrated to date is small. Our study examined if adjuvant chemotherapy is associated with improved cancer-specific survival in highrisk patients with stage II colon cancer. Methods: A retrospective review was performed on patients with stage II (T34N0M0) colon cancer in a multi-institutional database from 1999 to 2007. Additionally, histology slides were reviewed and cancer-specific survival data were obtained from the state cancer registry. Adverse features examined were perforation, obstruction, T4 disease, poor differentiation, nodal yield less than 12, lymphovascular invasion and perineural invasion. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Results: There were 458 patients in the study, with a median follow-up of 5.2 years. Four patients (0.8%) were lost to follow-up. There were 290 (63%) high-risk patients, defined as having at least one adverse feature. Patients who had adjuvant chemotherapy were significantly younger (median 61 years versus 72 years, P < 0.001) but had comparable ASA score (median 2 versus 2, P = 0.3). There was no significant survival benefit observed associated with any one factor or when grouped. In high-risk patients the 5-year cancer specific survival with adjuvant chemotherapy was 84.8% (95% CI 78.7–91.9) compared to surgery alone 92.7% (95% CI 88.5–96.1), P = 0.85). Conclusion: Adjuvant chemotherapy did not significantly improve cancer-specific survival in patients with stage II colon cancer with adverse features. Other markers for selecting appropriate patients for adjuvant treatment are required.
Introduction There is controversy surrounding the role of adjuvant chemotherapy in stage II colon cancer. Stage II colon cancer accounts for up to one-third of colorectal cancer (CRC) and the majority of affected patients have an excellent predicted 5-year survival of around 80%.1,2 However, around 10–30% of stage II patients have poorer survival associated with the presence of adverse features, such as advanced T stage, poor differentiation, tumour perforation and lymphovascular invasion (LVI).3–6 For this reason, current guidelines recommend that patients with high-risk features, especially young patients, be considered for © 2013 Royal Australasian College of Surgeons
adjuvant treatment.7–9 Adjuvant chemotherapy has only been shown to confer a 3–5% improvement in survival in patients with stage II colon cancer.7,10 Therefore, the small relative benefit of treatment should be considered against the significant increase in resources required to manage this group. The aim of this study was to review our own data to determine if poor prognostic factors predicted a survival benefit from adjuvant chemotherapy given for stage II colon cancer. We also examined factors that influence the decision to offer adjuvant chemotherapy in this setting. We hypothesized that while large studies with heterogeneous patients showed a small benefit with adjuvant chemotherapy, in clinical practice, no benefit would be realized. ANZ J Surg 84 (2014) 837–841
838
Methods A retrospective review of patients with CRC was conducted on the Northern Adelaide Colorectal Unit (NACU) database. The NACU comprises three public teaching hospitals in Adelaide and the database has been prospectively maintained from 1999 to 2007. In addition to patient demographic data, date of surgery, surgical details including operation performed and post-operative complications, pathology data including tumour site, TNM stage and grade are collected. American Society of Anaesthesiologists (ASA) score is also collected as a measure of patient co-morbidity. Patients were staged as stage I (T1-2N0M0), stage II (T3-4N0M0), stage III (any T,N1-2-M0) or stage IV (M1 metastatic), according to the AJCC TNM11 system. For the purposes of this study, patients were eligible for inclusion if they underwent resection for a histologically proven T3 or T4 node negative adenocarcinoma of the colon (defined as being above 15 cm from the anal verge). Patients with rectal cancer (defined as less than or equal to 15 cm from the anal verge) were excluded due to the potential confounding factor of neoadjuvant chemoradiation therapy. Patients with non-adenocarcinoma tumours, distant disease (M1) or residual local disease after resection (R1 or R2 resection) and either metachronous tumours within 5 years or synchronous tumours of a more advanced stage were excluded. Nodal micrometastasis (defined as isolated tumour cells
