Background: Clinical predictors of death and survival in surgical treatment of colon cancer are easily confounded by the modern adjuvant and neo-adjuvant chemotherapy. This study focuses on lethality and survival during implementation of ultra-radical surgery for colonic cancer prior to multimodal therapy. Methods: Retrospective observational follow-up study of 824 consecutive, unselected patients resected for Stage I, II, III and IV colon cancer from 1990 until 2000 at one tertiary centre, with a median follow-up of 45 months (0 - 202 months). Predictors for death were assessed by Cox regression analyses and log-rank test. The cause of death was obtained from the Norwegian Cause of Death Registry. Results: The relative survival rates were 86.3%, 71.9%, 50.3% and 6.6% in Stage I, II, III and IV, respectively. In 28.7% of the patients, the cause of death was other than colorectal cancer recur rence. The adjusted Cox regression model showed that higher age (1.04 (95% CI: 1.03; 1.05)), male gender (1.37 (1.14; 1.66)), emergency surgery (1.52 (1.21; 1.93)), left vs. right hemicolectomy (1.39 (1.03; 1.87)), and perioperative blood transfusion (1.25 (1.01; 1.55)) were predictors of reduced survival. Health without known comorbidity (0.71 (0.58; 0.88)), D2 versus D1 lymph node dissection (0.66 (0.53; 0.83)) and tumour Stage I, II, III versus Stage IV 0.10 (0.06; 0.16), 0.14 (0.11; 0.19), 0.23 (0.18; 0.30) were associated with prolonged survival. Conclusions: In 28.7% of the patients, the cause of death was other than colorectal cancer recurrence. Age, sex, comorbidity, emergency resec tion, lack of lymph node dissection, tumour stage, and preoperative blood transfusions are all significant predictors for reduced survival after surgery for colon cancer.
KeywordsColon CancerPredictors for SurvivalEmergency SurgeryLymph Node Dis-sectionBlood Transfusion
The Norwegian Cancer Registry. https://www.kreftregisteret.no/en
Walter, V., Jansen, L., Hoffmeister, M., Ulrich, A., Chang-Claude, J. and Brenner, H. (2015) Smoking and Survival of Colorectal Cancer Patients: Population-Based Study from Germany. International Journal of Cancer, 137, 1433-1445. https://doi.org/10.1002/ijc.29511
Hohenberger, W., Weber, K., Matzel, K., Papadopoulos, T. and Merkel, S. (2008) Standardized Surgery for Colonic Cancer: Complete Mesocolic Excision and Central Ligation-Technical Notes and Outcome. Colorectal Disease, 11, 354-365. https://doi.org/10.1111/j.1463-1318.2008.01735.x
Nikberg, M., Chabok, A., Letocha, H., Kindler, C., Glimelius, B. and Smetdh, K. (2016) Lymphovascular and Perineural Invasion in Stage II Rectal Cancer: A Report from the Swedish Colorectal Cancer Registry. Acta Oncologica, 55, 1418-1424. https://doi.org/10.1080/0284186X.2016.1230274
Tie, J., Wang, Y., Tomasetti, C., Li, L., Springer, S., Kinde, I., Silliman, N., Tacey, M., Wong, H.L., Christie, M., Kosmider, S., Skinner, I., Wong, R., Steel, M., Tran, B., Desai, J., Jones, I., Haydon, A., Hayes, T., Price, T.J., Strausberg, R.L., Diaz, L.A., Papadopoulos, N., Kinzler, K.W., Vogelstein, B. and Gibbs, P. (2016) Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer. Science Translational Medicine, 8, 346ra92. https://doi.org/10.1126/scitranslmed.aaf6219
The Norwegian Cause of Death Registry. http://ghdx.healthdata.org/series/norway-cause-death-registry
Statistics Norway. http://ssb.no
van Eeghen, E.E., Bakker, S.D., van Bochove, A. and Loffeld, R.J.L.F. (2015) Impact of Age and Comorbidity on Survival in Colorectal Cancer. Journal of Gastrointestinal Oncology, 6, 605-612.
Hayes, L., Forrest, L., Adams, J., Hidajat, M., Ben-Shlomo, Y., White, M. and Sharp, L. (2019) Age-Related Inequalities in Colon Cancer Treatment Persist over Time: A Population-Based Analysis. Journal of Epidemiology and Community Health, 73, 34-41. https://doi.org/10.1136/jech-2018-210842
Ommundsen, N., Wyller, T.B., Nesbakken, A., Jordh∅y, M.S., Bakka, A., Skovlund, E. and Rostoft, S. (2014) Frailty Is an Independent Predictor of Survival in Older Patients with Colorectal Cancer. Oncologist, 19, 1268-1275. https://doi.org/10.1634/theoncologist.2014-0237
R∅nning, B., Wyller, T.B., Nesbakken, A., Skovlund, E., Slaaen Jordh∅y, M.S., Bakka, A. and Rostoft, S. (2016) Quality of Life in Older and Frail Patients after Surgery for Colorectal Cancer—A Follow-Up Study. Journal of Geriatric Oncology, 7, 195-200. https://doi.org/10.1016/j.jgo.2016.03.002
Gaitonde, S.G., Nissan, A., Protic, M., Stojadinovic, A., Wainberg, Z.A., Chen, D.C. and Bilchik, A.J. (2017) Sex-Specific Differences in Colon Cancer When Quality Measures Are Adhered to: Results from International, Prospective, Multicenter Clinical Trials. Journal of the American College of Surgeons, 225, 85-92. https://doi.org/10.1016/j.jamcollsurg.2017.02.019
Breitenstein, S., Rickenbacher, A., Berdajs, D., Puhan, M., Clavien, P.-A. and Demartines, N. (2007) Systematic Evaluation of Surgical Strategies for Acute Malignant Left-Sided Colonic Obstruction. British Journal of Surgery, 94, 1451-1460. https://doi.org/10.1002/bjs.6007
Tekkis, P.P., Kinsman, R., Thompson, M.R. and Stamatakis, J.D. (2004) The Association of Coloproctology of Great Britain and Ireland Study of Large Bowel Obstruction Caused by Colorectal Cancer. Annals of Surgery, 240, 76-81. https://doi.org/10.1097/01.sla.0000130723.81866.75
Huijts, D.D., van Groningen, J.T., Guicherit, O.R., Dekker, J.W.T., van Bodegom-Vos, Bastiannet, E., Govaert, J.A., Wouters, M.W. and can de Mheen, P.J.M. (2018) Weekend Effect in Emergency Colon and Rectal Cancer Surgery: A Prospective Study Using Data from the Dutch Colorectal Audit. Journal of the National Comprehensive Cancer Network, 16, 735-741. https://doi.org/10.6004/jnccn.2018.7016
Biondo, S., Gálvez, A., Ramírez, E., Frago, R. and Kreisler, E. (2019) Emergency Surgery for Obstructing and Perforated Colon Cancer: Patterns of Recurrence and Prognostic Factors. Techniques in Coloproctology, 23, 1141-1161. https://doi.org/10.1007/s10151-019-02110-x
Oliphant, R., Nicholson, G.A., Horgan, P.G., Molloy, R.G., McMillan, D.C. and Morrison, D.S. (2013) West of Scotland Colorectal Cancer Managed Clinical Network. Contribution of Surgical Specialization to Improved Colorectal Cancer Survival. British Journal of Surgery, 100, 1388-1395. https://doi.org/10.1002/bjs.9227
Kwaan, M.R., Al-Refaie, W.B., Parsons, H.M., Chow, C.J., Rothenberger, D.A. and Habermann, E.B. (2013) Are Right-Sided Colectomy Outcomes Different from Left-Sided Colectomy Outcomes? Study of Patients with Colon Cancer in the ACS NSQIP Database. JAMA Surgery, 148, 504-510. https://doi.org/10.1001/jamasurg.2013.1205
Lim, D.R., Kuk, J.K., Kim, T. and Shin, E.J. (2017) Comparison of Oncological Outcomes of Right-Sided Colon Cancer versus Left-Sided Colon Cancer after Curative Resection: Which Side Is Better Outcome? Medicine (Baltimore), 96, e8241. https://doi.org/10.1097/MD.0000000000008241
Lee, L., Erkan, A., Alhassan, N., Kelly, J.J., Nassif, G.J., Albert, M.R. and Monson, J.R. (2018) Lower Survival after Right-Sided versus Left-Sided Colon Cancers: Is an Extended Lymphadenectomy the Answer? Surgical Oncology, 27, 449-455. https://doi.org/10.1016/j.suronc.2018.05.031
Benedix, F., Kube, R., Meyer, F., Schmidt, U., Gastinger, I., Lippert, H. and Colon/Rectum Carcinomas (Primary Tumor) Study Group (2010) Comparison of 17,641 Patients with Right- and Left-Sided Colon Cancer: Differences in Epidemiology, Perioperative Course, Histology, and Survival. Diseases of the Colon & Rectum, 53, 57-64. https://doi.org/10.1007/DCR.0b013e3181c703a4
Karachun, A., Petrov, A., Panaiotti, L., Voschinin, Y. and Ovchinnikova, T. (2019) Protocol for a Multicentre Randomized Clinical Trial Comparing Oncological Outcomes of D2 versus D3 Lymph Node Dissection in Colonic Cancer (COLD Trial). BJS Open, 3, 288-298. https://doi.org/10.1002/bjs5.50142
Lu, J.Y., Xu, L., Xue, H.D., Zhou, W.X., Xu, T., Qiu, H.Z., Wu, B., Lin, G.L. and Xiao, Y. (2016) The Radical Extent of Lymphadenectomy—D2 Dissection versus Complete Mesocolic Excision of Laparoscopic Right Colectomy for Right-Sided Colon Cancer (RELARC) Trial: Study Protocol for a Randomized Controlled Trial. Trials, 17, 582. https://doi.org/10.1186/s13063-016-1710-9
Patel, S.V., Brennan, K.E., Nanji, S., Karim, S., Merchant, S. and Booth, C.M. (2017) Peri-Operative Blood Transfusion for Resected Colon Cancer: Practice Patterns and Outcomes in a Population-Based Study. Cancer Epidemiology, 51, 35-40. https://doi.org/10.1016/j.canep.2017.10.006
Aquina, C.T., Blumberg, N., Becerra, A.Z., Boscoe, F.P., Schymura, M.J., Noyes, K., Monson, J.R.T. and Fleming, F.J. (2017) Association among Blood Transfusion, Sepsis, and Decreased Long-Term Survival after Colon Cancer Resection. Annals of Surgery, 266, 311-317. https://doi.org/10.1097/SLA.0000000000001990
Tarantino, I., Ukegjini, K., Warschkow, R., Schmied, B.M., Steffen, T., Ulrich, A. and Müller, S.A. (2013) Blood Transfusion Does Not Adversely Affect Survival after Elective Colon Cancer Resection: A Propensity Score Analysis. Langenbeck’s Archives of Surgery, 398, 841-849. https://doi.org/10.1007/s00423-013-1098-x
Amri, R., Dinaux, A.M., Leijssen, L.G.J., Kunitake, H., Bordeianou, L.G. and Berger, D.L. (2017) Do Packed Red Blood Cell Transfusions Really Worsen Oncologic Outcomes in Colon Cancer? Surgery, 162, 586-591. https://doi.org/10.1016/j.surg.2017.03.024
Rosander, E., Nordenvall, C., Sjövall, A., Hjern, F. and Holm, T. (2018) Management and Outcome after Multivisceral Resections in Patients with Locally Advanced Primary Colon Cancer. Diseases of the Colon & Rectum, 61, 454-460. https://doi.org/10.1097/DCR.0000000000001046
Klaver, C.E.L., Gietelink, L., Bemelman, W.A., Wouters, M.W.J.M., Wiggers, T., Tollenaar, R.A.E.M., Tanis, P.J. and Dutch Surgical Colorectal Audit Group (2017) Locally Advanced Colon Cancer: Evaluation of Current Clinical Practice and Treatment Outcomes at the Population Level. Journal of the National Comprehensive Cancer Network, 15, 181-190. https://doi.org/10.6004/jnccn.2017.0019
Otani, K., Kawai, K., Hata, K., Tanaka, T., Nishikawa, T., Sasaki, K., Kaneko, M., Murono, K., Emoto, S. and Nozawa, H. (2019) Colon Cancer with Perforation. Surgery Today, 49, 15-20. https://doi.org/10.1007/s00595-018-1661-8
Ludeman, L. and Shepherd, N.A. (2005) Serosal Involvement in Gastrointestinal Cancer: Its Assessment and Significance. Histopathology, 47, 123-131. https://doi.org/10.1111/j.1365-2559.2005.02189.x
Khoury, W., Lavery, I.C. and Kiran, R.P. (2012) Impact of Early Reoperation after Resection for Colorectal Cancer on Long-Term Oncological Outcomes. Colorectal Disease, 14, e117-e123. https://doi.org/10.1111/j.1463-1318.2011.02804.x
Saadat, L.V., Fields, A.C., Lyu, H., Urman, R.D., Whang, E.E., Goldberg, J., Bleday, R. and Melnitchouk, N. (2019) National Surgical Quality Improvement Program Analysis of Unplanned Reoperation in Patients Undergoing Low Anterior Resection or Abdominoperineal Resection for Rectal Cancer. Surgery, 165, 602-607. https://doi.org/10.1016/j.surg.2018.08.016
Bakker, I.S., Grossmann, I., Hennemann, D., Havenga, K. and Wiggers, T. (2014) Risk Factors for Anastomotic Leakage and Leak-Related Mortality after Colonic Cancer Surgery in a Nationwide Audit. British Journal of Surgery, 101, 424-432. https://doi.org/10.1002/bjs.9395
McDermott, F.D., Heeney, A., Kelly, M.E., Steele, R.J., Carlson, G.L. and Winter, D.C. (2015) Systematic Review of Preoperative, Intraoperative and Postoperative Risk Factors for Colorectal Anastomotic Leaks. British Journal of Surgery, 102, 462-479. https://doi.org/10.1002/bjs.9697