Letters
Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0965. Author Contributions: Drs Kelley and Johnson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Crawford. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Kelley, Johnson. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Kelley, Gardiner. Administrative, technical, or material support: Crawford, Johnson. Study supervision: Thomas. Conflict of Interest Disclosures: None reported. Previous Presentation: This paper was presented at the 86th Annual Meeting of the Pacific Coast Surgical Association; February 20, 2015; Monterey, California. 1. Sun Y, Wei W, Yang HW, Liu JL. Clinical usefulness of breast-specific gamma imaging as an adjunct modality to mammography for diagnosis of breast cancer: a systemic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2013;40(3): 450-463. 2. Kieper D, Brem RF, Hoeffer R, Keppel C, Wymer D. Detecting infiltrating lobular carcinoma using scintimammographic breast specific gamma imaging. Phys Med. 2006;21(suppl 1):125-127. 3. Brem RF, Ioffe M, Rapelyea JA, et al. Invasive lobular carcinoma: detection with mammography, sonography, MRI, and breast-specific gamma imaging. AJR Am J Roentgenol. 2009;192(2):379-383. 4. Coover LR, Caravaglia G, Kuhn P. Scintimammography with dedicated breast camera detects and localizes occult carcinoma. J Nucl Med. 2004;45(4): 553-558. 5. Brem RF, Floerke AC, Rapelyea JA, Teal C, Kelly T, Mathur V. Breast-specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer. Radiology. 2008;247(3):651-657. 6. Hendrick RE. Radiation doses and cancer risks from breast imaging studies. Radiology. 2010;257(1):246-253.
COMMENT & RESPONSE
Less Surgery, Improved Survival From Stage IV Colorectal Cancer? To the Editor Hu et al1 report improved survival for patients with metastatic colorectal cancer over time and note that this corresponds to a decrease in the rate of surgery for the primary lesion. Based on the data, they suggest that resections for synchronous primary lesions may be overused. There are a number of concerns in making such a broad conclusion. Improved survival from metastatic colorectal cancer has occurred because of a combination of factors, including the improved use of systemic therapy and metastasectomy.2 Partly based on the advances in systemic therapy associated with significantly higher response rates, a review of the role of primary resection has occurred. Data were emerging that suggested that the risk of complications related to withholding resection of the primary lesion was no higher than the risk of having surgery prior to chemotherapy.3 This had led to more clinicians deferring resection of the primary lesion. However, there is increasing evidence that for synchronous metastatic colorectal cancer, resection of the primary lesion may be associated with an overall survival benefit, and this is noted briefly by Hu et al. 1 Importantly, the recently published pooled analysis of 810 patients from 4 randomized trials gives very strong evidence for this argument.4 The median overall survival was 19.2 months for patients who had a resection prior to chemotherapy and 13.3 818
months for patients who did not (hazard ratio, 0.54 [95% CI, 0.45-0.64]; P < .001). This pooled analysis4 also reported an association with improved progression-free survival. Importantly, multivariate analysis showed resection to be an independent predictor of overall survival. Why overall survival may be improved remains unclear, although prevention of colonic complications may play a role or, as others have hypothesized, a change in the angiogenesis environment may also be a factor.5 Several other developments are also worth noting. Improvements in surgical techniques, such as laparoscopic surgery, have decreased the potential morbidity associated with surgery. In addition, the increased risks of emergency surgery in the context of angiogenesis inhibitors such as bevacizumab tend to favor initial resection. Moreover, the effect of surgery on quality of life has never been evaluated. Randomized trials are required to address the role of palliative surgery, but such studies have proved extremely difficult to perform. It is our view that the role of palliative resection of the primary tumor remains an open question in many cases, and this approach might in fact constitute optimal management. Arguably, primary tumor resection may be not overused but underused. Timothy J. Price, MBBS, FRACP, DHSc Niall Tebbutt, MBBS, FRACP, PhD Amanda R. Townsend, MBBS, FRACP Author Affiliations: The Queen Elizabeth Hospital and University of Adelaide, Woodville, South Australia, Australia (Price, Townsend); Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, Victoria, Australia. (Tebbutt). Corresponding Author: Timothy J. Price, MBBS, FRACP, DHSc, The Queen Elizabeth Hospital and University of Adelaide, 28 Woodville Rd, Woodville, South Australia, Australia 5011 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0680. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677-3683. 3. Tebbutt NC, Norman AR, Cunningham D, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 2003;52(4):568-573. 4. Faron M, Pignon JP, Malka D, et al. Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? a pooled analysis of individual data from four randomised trials. Eur J Cancer. 2015;51(2):166-176. 5. van der Wal GE, Gouw AS, Kamps JA, et al. Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil. Ann Surg. 2012;255(1):86-94.
To the Editor We were surprised at the conclusions reached by Hu et al1 in their analysis of rates of primary tumor resection (PTR) and of survival of patients with metastatic colorectal cancer (MCRC) over time. Specifically, they have concluded that decreasing rates of PTR have directly contributed to the observed improvement in overall survival for patients with MCRC over a 22-year period, despite not providing an explanation as
JAMA Surgery August 2015 Volume 150, Number 8 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
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Letters
to how these 2 seemingly distinct data points are linked and despite an obvious alternative explanation for survival gains. Although we agree that systemic therapy is usually the appropriate therapy for the management of MCRC as per guidelines, the initial management of the primary tumor is a distinct issue that requires a careful multidisciplinary review. Case-by-case considerations include primary symptoms and the specific risks of leaving the tumor intact, which must be weighed against the risks posed by not immediately treating metastatic disease with systemic therapy and also must take into account fitness for surgery and/or chemotherapy/ biologics. There are indeed multiple arguments against PTR in individual cases, including the risk of operative morbidity and mortality and the potential delays in commencing systemic therapies known to significantly prolong survival. However, multiple series have suggested a survival gain from PTR, and a meta-analysis2 reported significant survival gains of many months. A recent study 3 examining changes in systemic inflammation after PTR has, for the first time to our knowledge, provided a possible biological explanation for any survival gain. Furthermore, we would suggest that survival gains over the time period examined are best explained by improvements in systemic therapy, with median survival rates in studies of MCRC conducted in the final years of the cohort examined by Hu et al1 approaching 30 months, compared with only 12 months for the early period of their cohort when only 5-fluorouracil was available.4,5 An association between decreasing PTR rates and improved survival over time is not evidence that leaving the primary tumor intact improves survival; indeed, it is questionable whether there is any link between these 2 outcomes. Furthermore, some data support the opposite (ie, that PTR improves survival). Until there are completed randomized trials that better inform the management of the primary tumor in patients presenting with MCRC, good clinical judgment in a multidisciplinary setting is required to decide whether a primary tumor should be resected (or not) prior to commencing systemic therapy that will substantially prolong survival. Rachel Wong, MBBS(Hons), FRACP Peter Gibbs, MBBS, FRACP, MD Author Affiliations: Department of Medical Oncology, Eastern Health, Monash University, Box Hill, Victoria, Australia (Wong); Walter and Eliza Hall Institute of Medical Research, Department of Medical Oncology, Royal Melbourne and Western Hospitals, Parkville, Melbourne, Victoria, Australia (Gibbs). Corresponding Author: Rachel Wong, MBBS(Hons), FRACP, Department of Medical Oncology, Eastern Health, Monash University, PO Box 94, Box Hill, Victoria, Australia 3128 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.1331. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Stillwell AP, Buettner PG, Ho YH. Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone. World J Surg. 2010;34(4):797-807. 3. Turner N, Tran P, Tran PV, et al. Primary tumor resection in patients with metastatic colorectal cancer is associated with reversal of systemic
jamasurgery.com
inflammation and improved survival [published online March 7, 2015]. Clin Colorectal Cancer. doi:10.1016/j.clcc.2015.02.004. 4. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-1075. 5. Poon MA, O’Connell MJ, Moertel CG, et al. Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol. 1989;7(10): 1407-1418.
In Reply In our recent study entitled “Time Trend Analysis of Primary Tumor Resection for Stage IV Colorectal Cancer: Less Surgery, Improved Survival,” 1 we noted a trend toward improved survival despite decreasing primary tumor resection (PTR) rates for patients presenting with unresectable metastatic colorectal cancer (MCRC). We observed improvements in survival that coincided with the availability of new systemic treatment options. However, more than 50% of patients who present with MCRC are still undergoing PTR. Based on these results, we concluded that PTR may be overused among patients with MCRC. As noted by Price and colleagues, to date, little is known about the effect of PTR on survival. Although multiple retrospective studies have associated PTR with a survival benefit, these studies are subject to the strong confounding effects of treatment selection, and survivor time biases limit the interpretation of their findings (eg, patients undergoing PTR may be less likely than patients not undergoing PTR to have an advanced disease burden or comorbid conditions). Although a pooled secondary analysis of randomized trials of systemic chemotherapy for MCRC indicated that improved overall survival was associated with PTR prior to the initiation of chemotherapy (median overall survival, 19.2 months),2 the decision to undergo PTR was not randomized and may reflect a number of factors both related and unrelated to the patient’s underlying tumor burden. Furthermore, similar survival results can be obtained for patients with MCRC and intact primary tumors with systemic therapy.3 Moreover, while indeed technical advances such as laparoscopic surgery may have reduced the potential morbidity of surgery, even a laparoscopic colectomy still carries significant risk, and the degree to which laparoscopy mitigates morbidity in the setting of unresectable metastatic disease is less clear.4 We agree with Wong and Gibbs that the role of PTR has to be considered on a case-by-case basis. We recognize that there is a group of patients who require palliative resection of their primary tumor (ie, patients with obstructive symptoms or patients who are likely to develop them, or patients who are bleeding), and we agree that the role of PTR should remain an open question, but at this time it should be reserved for highly select patients. Our analysis showed a temporal association between the decreasing rate of PTR and improved survival (ie, that survival rates improved despite a lower rate of PTR). However, our study was not designed to specifically address the question perhaps posed by Price and colleagues and Wong and Gibbs: does PTR improve survival? Until the confounding effects can be mitigated, the interpretation of retrospective analyses that show PTR-associated (Reprinted) JAMA Surgery August 2015 Volume 150, Number 8
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
819
Letters
survival benefit is fraught with hazard and should be done cautiously. These lingering questions emphasize the need to support the ongoing randomized trials of PTR for patients with MCRC.5
4. Zheng Z, Jemal A, Lin CC, Hu CY, Chang GJ. Comparative effectiveness of laparoscopy vs open colectomy among nonmetastatic colon cancer patients: an analysis using the National Cancer Data Base. J Natl Cancer Inst. 2015;107(3):dju491.
Chung-Yuan Hu, MPH, PhD Christina E. Bailey, MD, MS George J. Chang, MD, MS
5. ‘t Lam-Boer J, Mol L, Verhoef C, de Haan AF, et al. The CAIRO4 study: the role of surgery of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastases of colorectal cancer—a randomized phase III study of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2014;14:741.
Author Affiliations: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston (Hu, Bailey, Chang); Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston (Chang).
CORRECTION
Corresponding Author: George J. Chang, MD, MS, Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, FCT17.5022, 1515 Holcombe Blvd, Unit 1484, Houston, TX 77030 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0683. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Faron M, Pignon JP, Malka D, et al. Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? a pooled analysis of individual data from four randomised trials. Eur J Cancer. 2015;51(2):166-176. 3. McCahill LE, Yothers G, Sharif S, et al. Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically
820
unresectable metastatic colon cancer and an intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10. J Clin Oncol. 2012;30(26):3223-3228.
Errors in the Author Affiliations and Corresponding Author Address: In the Original Investigation titled “Survival Benefit of Breast Surgery for Low-Grade Ductal Carcinoma In Situ: A Population-Based Cohort Study” published online June 3, 2015, in JAMA Surgery (doi:10.1001/jamasurg.2015.0876), errors appeared in the Author Affiliations and Corresponding Author address. Stephanie Wong, MD, should be affiliated with Harvard School of Public Health instead of Harvard Medical School. Yasuaki Sagara, MD, should have Harvard Medical School listed as his affiliation in the Corresponding Author address instead of Harvard School of Public Health. This article was corrected online. Error in Reference Numbering: In the Original Investigation titled “β-Blockade and Operative Mortality in Noncardiac Surgery: Harmful or Helpful?” published online May 27, 2015, in JAMA Surgery,1 references 16-27 were inadvertently numbered incorrectly. This article was corrected online. 1. Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. β-Blockade and operative mortality in noncardiac surgery: Harmful or Helpful? [published online May 27, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.86.
JAMA Surgery August 2015 Volume 150, Number 8 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
jamasurgery.com
Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0965. Author Contributions: Drs Kelley and Johnson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Crawford. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Kelley, Johnson. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Kelley, Gardiner. Administrative, technical, or material support: Crawford, Johnson. Study supervision: Thomas. Conflict of Interest Disclosures: None reported. Previous Presentation: This paper was presented at the 86th Annual Meeting of the Pacific Coast Surgical Association; February 20, 2015; Monterey, California. 1. Sun Y, Wei W, Yang HW, Liu JL. Clinical usefulness of breast-specific gamma imaging as an adjunct modality to mammography for diagnosis of breast cancer: a systemic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2013;40(3): 450-463. 2. Kieper D, Brem RF, Hoeffer R, Keppel C, Wymer D. Detecting infiltrating lobular carcinoma using scintimammographic breast specific gamma imaging. Phys Med. 2006;21(suppl 1):125-127. 3. Brem RF, Ioffe M, Rapelyea JA, et al. Invasive lobular carcinoma: detection with mammography, sonography, MRI, and breast-specific gamma imaging. AJR Am J Roentgenol. 2009;192(2):379-383. 4. Coover LR, Caravaglia G, Kuhn P. Scintimammography with dedicated breast camera detects and localizes occult carcinoma. J Nucl Med. 2004;45(4): 553-558. 5. Brem RF, Floerke AC, Rapelyea JA, Teal C, Kelly T, Mathur V. Breast-specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer. Radiology. 2008;247(3):651-657. 6. Hendrick RE. Radiation doses and cancer risks from breast imaging studies. Radiology. 2010;257(1):246-253.
COMMENT & RESPONSE
Less Surgery, Improved Survival From Stage IV Colorectal Cancer? To the Editor Hu et al1 report improved survival for patients with metastatic colorectal cancer over time and note that this corresponds to a decrease in the rate of surgery for the primary lesion. Based on the data, they suggest that resections for synchronous primary lesions may be overused. There are a number of concerns in making such a broad conclusion. Improved survival from metastatic colorectal cancer has occurred because of a combination of factors, including the improved use of systemic therapy and metastasectomy.2 Partly based on the advances in systemic therapy associated with significantly higher response rates, a review of the role of primary resection has occurred. Data were emerging that suggested that the risk of complications related to withholding resection of the primary lesion was no higher than the risk of having surgery prior to chemotherapy.3 This had led to more clinicians deferring resection of the primary lesion. However, there is increasing evidence that for synchronous metastatic colorectal cancer, resection of the primary lesion may be associated with an overall survival benefit, and this is noted briefly by Hu et al. 1 Importantly, the recently published pooled analysis of 810 patients from 4 randomized trials gives very strong evidence for this argument.4 The median overall survival was 19.2 months for patients who had a resection prior to chemotherapy and 13.3 818
months for patients who did not (hazard ratio, 0.54 [95% CI, 0.45-0.64]; P < .001). This pooled analysis4 also reported an association with improved progression-free survival. Importantly, multivariate analysis showed resection to be an independent predictor of overall survival. Why overall survival may be improved remains unclear, although prevention of colonic complications may play a role or, as others have hypothesized, a change in the angiogenesis environment may also be a factor.5 Several other developments are also worth noting. Improvements in surgical techniques, such as laparoscopic surgery, have decreased the potential morbidity associated with surgery. In addition, the increased risks of emergency surgery in the context of angiogenesis inhibitors such as bevacizumab tend to favor initial resection. Moreover, the effect of surgery on quality of life has never been evaluated. Randomized trials are required to address the role of palliative surgery, but such studies have proved extremely difficult to perform. It is our view that the role of palliative resection of the primary tumor remains an open question in many cases, and this approach might in fact constitute optimal management. Arguably, primary tumor resection may be not overused but underused. Timothy J. Price, MBBS, FRACP, DHSc Niall Tebbutt, MBBS, FRACP, PhD Amanda R. Townsend, MBBS, FRACP Author Affiliations: The Queen Elizabeth Hospital and University of Adelaide, Woodville, South Australia, Australia (Price, Townsend); Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, Victoria, Australia. (Tebbutt). Corresponding Author: Timothy J. Price, MBBS, FRACP, DHSc, The Queen Elizabeth Hospital and University of Adelaide, 28 Woodville Rd, Woodville, South Australia, Australia 5011 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0680. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677-3683. 3. Tebbutt NC, Norman AR, Cunningham D, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 2003;52(4):568-573. 4. Faron M, Pignon JP, Malka D, et al. Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? a pooled analysis of individual data from four randomised trials. Eur J Cancer. 2015;51(2):166-176. 5. van der Wal GE, Gouw AS, Kamps JA, et al. Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil. Ann Surg. 2012;255(1):86-94.
To the Editor We were surprised at the conclusions reached by Hu et al1 in their analysis of rates of primary tumor resection (PTR) and of survival of patients with metastatic colorectal cancer (MCRC) over time. Specifically, they have concluded that decreasing rates of PTR have directly contributed to the observed improvement in overall survival for patients with MCRC over a 22-year period, despite not providing an explanation as
JAMA Surgery August 2015 Volume 150, Number 8 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
jamasurgery.com
Letters
to how these 2 seemingly distinct data points are linked and despite an obvious alternative explanation for survival gains. Although we agree that systemic therapy is usually the appropriate therapy for the management of MCRC as per guidelines, the initial management of the primary tumor is a distinct issue that requires a careful multidisciplinary review. Case-by-case considerations include primary symptoms and the specific risks of leaving the tumor intact, which must be weighed against the risks posed by not immediately treating metastatic disease with systemic therapy and also must take into account fitness for surgery and/or chemotherapy/ biologics. There are indeed multiple arguments against PTR in individual cases, including the risk of operative morbidity and mortality and the potential delays in commencing systemic therapies known to significantly prolong survival. However, multiple series have suggested a survival gain from PTR, and a meta-analysis2 reported significant survival gains of many months. A recent study 3 examining changes in systemic inflammation after PTR has, for the first time to our knowledge, provided a possible biological explanation for any survival gain. Furthermore, we would suggest that survival gains over the time period examined are best explained by improvements in systemic therapy, with median survival rates in studies of MCRC conducted in the final years of the cohort examined by Hu et al1 approaching 30 months, compared with only 12 months for the early period of their cohort when only 5-fluorouracil was available.4,5 An association between decreasing PTR rates and improved survival over time is not evidence that leaving the primary tumor intact improves survival; indeed, it is questionable whether there is any link between these 2 outcomes. Furthermore, some data support the opposite (ie, that PTR improves survival). Until there are completed randomized trials that better inform the management of the primary tumor in patients presenting with MCRC, good clinical judgment in a multidisciplinary setting is required to decide whether a primary tumor should be resected (or not) prior to commencing systemic therapy that will substantially prolong survival. Rachel Wong, MBBS(Hons), FRACP Peter Gibbs, MBBS, FRACP, MD Author Affiliations: Department of Medical Oncology, Eastern Health, Monash University, Box Hill, Victoria, Australia (Wong); Walter and Eliza Hall Institute of Medical Research, Department of Medical Oncology, Royal Melbourne and Western Hospitals, Parkville, Melbourne, Victoria, Australia (Gibbs). Corresponding Author: Rachel Wong, MBBS(Hons), FRACP, Department of Medical Oncology, Eastern Health, Monash University, PO Box 94, Box Hill, Victoria, Australia 3128 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.1331. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Stillwell AP, Buettner PG, Ho YH. Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone. World J Surg. 2010;34(4):797-807. 3. Turner N, Tran P, Tran PV, et al. Primary tumor resection in patients with metastatic colorectal cancer is associated with reversal of systemic
jamasurgery.com
inflammation and improved survival [published online March 7, 2015]. Clin Colorectal Cancer. doi:10.1016/j.clcc.2015.02.004. 4. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-1075. 5. Poon MA, O’Connell MJ, Moertel CG, et al. Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol. 1989;7(10): 1407-1418.
In Reply In our recent study entitled “Time Trend Analysis of Primary Tumor Resection for Stage IV Colorectal Cancer: Less Surgery, Improved Survival,” 1 we noted a trend toward improved survival despite decreasing primary tumor resection (PTR) rates for patients presenting with unresectable metastatic colorectal cancer (MCRC). We observed improvements in survival that coincided with the availability of new systemic treatment options. However, more than 50% of patients who present with MCRC are still undergoing PTR. Based on these results, we concluded that PTR may be overused among patients with MCRC. As noted by Price and colleagues, to date, little is known about the effect of PTR on survival. Although multiple retrospective studies have associated PTR with a survival benefit, these studies are subject to the strong confounding effects of treatment selection, and survivor time biases limit the interpretation of their findings (eg, patients undergoing PTR may be less likely than patients not undergoing PTR to have an advanced disease burden or comorbid conditions). Although a pooled secondary analysis of randomized trials of systemic chemotherapy for MCRC indicated that improved overall survival was associated with PTR prior to the initiation of chemotherapy (median overall survival, 19.2 months),2 the decision to undergo PTR was not randomized and may reflect a number of factors both related and unrelated to the patient’s underlying tumor burden. Furthermore, similar survival results can be obtained for patients with MCRC and intact primary tumors with systemic therapy.3 Moreover, while indeed technical advances such as laparoscopic surgery may have reduced the potential morbidity of surgery, even a laparoscopic colectomy still carries significant risk, and the degree to which laparoscopy mitigates morbidity in the setting of unresectable metastatic disease is less clear.4 We agree with Wong and Gibbs that the role of PTR has to be considered on a case-by-case basis. We recognize that there is a group of patients who require palliative resection of their primary tumor (ie, patients with obstructive symptoms or patients who are likely to develop them, or patients who are bleeding), and we agree that the role of PTR should remain an open question, but at this time it should be reserved for highly select patients. Our analysis showed a temporal association between the decreasing rate of PTR and improved survival (ie, that survival rates improved despite a lower rate of PTR). However, our study was not designed to specifically address the question perhaps posed by Price and colleagues and Wong and Gibbs: does PTR improve survival? Until the confounding effects can be mitigated, the interpretation of retrospective analyses that show PTR-associated (Reprinted) JAMA Surgery August 2015 Volume 150, Number 8
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
819
Letters
survival benefit is fraught with hazard and should be done cautiously. These lingering questions emphasize the need to support the ongoing randomized trials of PTR for patients with MCRC.5
4. Zheng Z, Jemal A, Lin CC, Hu CY, Chang GJ. Comparative effectiveness of laparoscopy vs open colectomy among nonmetastatic colon cancer patients: an analysis using the National Cancer Data Base. J Natl Cancer Inst. 2015;107(3):dju491.
Chung-Yuan Hu, MPH, PhD Christina E. Bailey, MD, MS George J. Chang, MD, MS
5. ‘t Lam-Boer J, Mol L, Verhoef C, de Haan AF, et al. The CAIRO4 study: the role of surgery of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastases of colorectal cancer—a randomized phase III study of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2014;14:741.
Author Affiliations: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston (Hu, Bailey, Chang); Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston (Chang).
CORRECTION
Corresponding Author: George J. Chang, MD, MS, Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, FCT17.5022, 1515 Holcombe Blvd, Unit 1484, Houston, TX 77030 ([email protected]). Published Online: June 24, 2015. doi:10.1001/jamasurg.2015.0683. Conflict of Interest Disclosures: None reported. 1. Hu CY, Bailey CE, You YN, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245-251. 2. Faron M, Pignon JP, Malka D, et al. Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? a pooled analysis of individual data from four randomised trials. Eur J Cancer. 2015;51(2):166-176. 3. McCahill LE, Yothers G, Sharif S, et al. Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically
820
unresectable metastatic colon cancer and an intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10. J Clin Oncol. 2012;30(26):3223-3228.
Errors in the Author Affiliations and Corresponding Author Address: In the Original Investigation titled “Survival Benefit of Breast Surgery for Low-Grade Ductal Carcinoma In Situ: A Population-Based Cohort Study” published online June 3, 2015, in JAMA Surgery (doi:10.1001/jamasurg.2015.0876), errors appeared in the Author Affiliations and Corresponding Author address. Stephanie Wong, MD, should be affiliated with Harvard School of Public Health instead of Harvard Medical School. Yasuaki Sagara, MD, should have Harvard Medical School listed as his affiliation in the Corresponding Author address instead of Harvard School of Public Health. This article was corrected online. Error in Reference Numbering: In the Original Investigation titled “β-Blockade and Operative Mortality in Noncardiac Surgery: Harmful or Helpful?” published online May 27, 2015, in JAMA Surgery,1 references 16-27 were inadvertently numbered incorrectly. This article was corrected online. 1. Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. β-Blockade and operative mortality in noncardiac surgery: Harmful or Helpful? [published online May 27, 2015]. JAMA Surg. doi:10.1001/jamasurg.2015.86.
JAMA Surgery August 2015 Volume 150, Number 8 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a University of California - San Diego User on 01/23/2016
jamasurgery.com
