Top

Published in:

20-06-2023 | Colon Cancer | Original Article

Adjuvant Chemotherapy Is Associated with Improved Survival for Stage III Colon Cancer When Initiated Beyond 8 Weeks

Authors: Fasih Ali Ahmed, MD, Victoria S. Wu, BA, Hanna Kakish, MD, Luke Rothermel, MD, MPH, Sharon L. Stein, MD, Emily Steinhagen, MD, Richard Hoehn, MD

Published in: Journal of Gastrointestinal Surgery | Issue 9/2023

Abstract

Background

The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant chemotherapy (AC) within 6–8 weeks of surgical resection for patients with stage III colon cancer. However, postoperative complications or prolonged surgical recovery may affect the receipt of AC. The aim of this study was to assess the utility of AC for patients with prolonged postoperative recovery.

Methods

We queried the National Cancer Database (2010–2018) for patients with resected stage III colon cancer. Patients were categorized as having either normal or prolonged length of stay (PLOS: >7 days, 75th percentile). Multivariable Cox proportional hazard regression and logistic regressions were used to identify factors associated with overall survival and receipt of AC.

Results

Of the 113,387 patients included, 30,196 (26.6%) experienced PLOS. Of the 88,115 (77.7%) patients who received AC, 22,707 (25.8%) initiated AC more than 8 weeks after surgery. Patients with PLOS were less likely to receive AC (71.5% vs. 80.0%, OR: 0.72, 95%CI=0.70–0.75) and displayed inferior survival (75 vs. 116 months, HR: 1.39, 95%CI=1.36–1.43). Receipt of AC was also associated with patient factors such as high socioeconomic status, private insurance, and White race (p<0.05 for all). AC within and after 8 weeks of surgery was associated with improved survival for patients with both normal LOS and PLOS (normal LOS: <8 weeks HR: 0.56, 95% CI: 0.54–0.59, >8 weeks HR: 0.68, 95% CI: 0.65–0.71; PLOS: <8 weeks HR: 0.51, 95% CI: 0.48–0.54, >8 weeks HR: 0.63, 95% CI 0.60–0.67). AC was associated with significantly improved survival if initiated up to 15 weeks postoperatively (normal LOS: HR: 0.72, 95%CI=0.61–0.85; PLOS: HR: 0.75, 95%CI=0.62–0.90), and very few patients (<3.0%) initiated AC beyond this time.

Conclusion

Receipt of AC for stage III colon cancer may be affected by surgical complications or otherwise prolonged recovery. Timely and even delayed AC (>8 weeks) are both associated with improved overall survival. These findings highlight the importance of delivering guideline-based systemic therapies, even after complicated surgical recovery.

R. L. Siegel, K. D. Miller, H. E. Fuchs, and A. Jemal, “Cancer statistics, 2022,” CA: A Cancer Journal for Clinicians, 72, 1, 7–33, 2022, doi: https://doi.org/10.3322/caac.21708.CrossRefPubMed

J. Tashiro et al., “Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings,” World Journal of Surgical Oncology, 12, 1, 145, 2014, doi: https://doi.org/10.1186/1477-7819-12-145.CrossRefPubMedPubMedCentral

G. Yothers et al., “Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses,” J Clin Oncol, 29, 28, 3768–3774, 2011, doi: https://doi.org/10.1200/JCO.2011.36.4539.CrossRefPubMedPubMedCentral

T. André et al., “Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer,” N Engl J Med, 350, 23, 2343–2351, 2004, doi: https://doi.org/10.1056/NEJMoa032709.CrossRefPubMed

“Guidelines Detail,” NCCN. https://www.nccn.org/guidelines/guidelines-detail (accessed Nov. 07, 2022).

R. Veldkamp et al., “Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial,” Lancet Oncol, 6, 7, 477–484, 2005, doi: https://doi.org/10.1016/S1470-2045(05)70221-7.CrossRefPubMed

A. M. Lacy et al., “Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial,” Lancet, 359, 9325, 2224–2229, 2002, doi: https://doi.org/10.1016/S0140-6736(02)09290-5.CrossRefPubMed

S. Yamamoto et al., “Short-term surgical outcomes from a randomized controlled trial to evaluate laparoscopic and open D3 dissection for stage II/III colon cancer: Japan Clinical Oncology Group Study JCOG 0404,” Ann Surg, 260, 1, 23–30, 2014, doi: https://doi.org/10.1097/SLA.0000000000000499.CrossRefPubMed

“A Comparison of Laparoscopically Assisted and Open Colectomy for Colon Cancer,” N Engl J Med, 350, 20, 2050–2059, 2004, doi: https://doi.org/10.1056/NEJMoa032651.

10.

L. G. M. van der Geest et al., “Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer,” Colorectal Dis, 15, 10, e582-591, 2013, doi: https://doi.org/10.1111/codi.12288.CrossRefPubMed

11.

R. P. Merkow et al., “Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer,” Ann Surg, 258, 6, 847–853, 2013, doi: https://doi.org/10.1097/SLA.0000000000000312.CrossRefPubMed

12.

“Participant User Files,” ACS. https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/puf/ (accessed Nov. 07, 2022).

13.

D. S. Swords, S. J. Mulvihill, B. S. Brooke, D. E. Skarda, M. A. Firpo, and C. L. Scaife, “Disparities in utilization of treatment for clinical stage I-II pancreatic adenocarcinoma by area socioeconomic status and race/ethnicity,” Surgery, 165, 4, 751–759, 2019, doi: https://doi.org/10.1016/j.surg.2018.10.035.CrossRefPubMed

14.

F. A. Ahmed et al., “Disparities in treatment and survival for patients with isolated colorectal liver metastases,” Surgery, 2022, doi: https://doi.org/10.1016/j.surg.2022.09.026.

15.

M. C. Turner et al., “Delay in Adjuvant Chemotherapy and Survival Advantage in Stage III Colon Cancer,” Journal of the American College of Surgeons, 226, 4, 670–678, 2018, doi: https://doi.org/10.1016/j.jamcollsurg.2017.12.048.CrossRefPubMed

16.

R. W. Krell, M. E. Girotti, and J. B. Dimick, “Extended length of stay after surgery: complications, inefficient practice, or sick patients?,” JAMA Surg, 149, 8, 815–820, 2014, doi: https://doi.org/10.1001/jamasurg.2014.629.CrossRefPubMedPubMedCentral

17.

M. Elshami et al., “Average treatment effect of facility hepatopancreatobiliary cancer volume on survival of non-resected pancreatic adenocarcinoma,” HPB, 2022, doi: https://doi.org/10.1016/j.hpb.2022.07.007.

18.

I. S. F. Lima, Y. Yasui, A. Scarfe, and M. Winget, “Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada,” Cancer, 117, 16, 3833–3840, 2011, doi: https://doi.org/10.1002/cncr.25954.CrossRefPubMed

19.

W. Y. Cheung, B. A. Neville, and C. C. Earle, “Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer,” Dis Colon Rectum, 52, 6, 1054–1063; discussion 1064, 2009, doi: https://doi.org/10.1007/DCR.0b013e3181a51173.

20.

A. Mazmudar, J. Castle, A. D. Yang, and D. J. Bentrem, “The association of length of hospital stay with readmission after elective pancreatic resection,” J Surg Oncol, 118, 1, pp. 7–14, 2018, doi: https://doi.org/10.1002/jso.25093.CrossRefPubMed

21.

E. B. Schneider et al., “Early versus late hospital readmission after pancreaticoduodenectomy,” J Surg Res, 196, 1, 74–81, 2015, doi: https://doi.org/10.1016/j.jss.2015.02.043.CrossRefPubMed

22.

E. Sadot et al., “Readmission after pancreatic resection: causes and causality pattern,” Ann Surg Oncol, 21, 13, pp. 4342–4350, 2014, doi: https://doi.org/10.1245/s10434-014-3841-0.CrossRefPubMedPubMedCentral

23.

O. Hyder et al., “Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States,” JAMA Surg, 148, 12, 1095–1102, 2013, doi: https://doi.org/10.1001/jamasurg.2013.2509.CrossRefPubMedPubMedCentral

24.

Z. J. Kastenberg, J. M. Morton, B. C. Visser, J. A. Norton, and G. A. Poultsides, “Hospital readmission after a pancreaticoduodenectomy: an emerging quality metric?,” HPB (Oxford), 15, 2, 142–148, 2013, doi: https://doi.org/10.1111/j.1477-2574.2012.00563.x.CrossRefPubMed

25.

S. A. Ahmad et al., “Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients,” Ann Surg, 256, 3, 529–537, 2012, doi: https://doi.org/10.1097/SLA.0b013e318265ef0b.CrossRefPubMed

26.

T. S. Kent, T. E. Sachs, M. P. Callery, and C. M. Vollmer, “Readmission after major pancreatic resection: a necessary evil?,” J Am Coll Surg, 213, 4, 515–523, 2011, doi: https://doi.org/10.1016/j.jamcollsurg.2011.07.009.CrossRefPubMed

27.

M. K. Krzyzanowska, M. M. Regan, M. Powell, C. C. Earle, and J. C. Weeks, “Impact of patient age and comorbidity on surgeon versus oncologist preferences for adjuvant chemotherapy for stage III colon cancer,” J Am Coll Surg, 208, 2, 202–209, 2009, doi: https://doi.org/10.1016/j.jamcollsurg.2008.10.016.CrossRefPubMed

28.

M. Buitrago-Ruiz, I. Martinez-Nicolas, and V. Soria-Aledo, “Validation of prolonged length of stay as a reliable measure of failure to rescue in colorectal surgery,” Asian J Surg, S1015-9584(22)00103–8, 2022, doi: https://doi.org/10.1016/j.asjsur.2022.02.003.CrossRef

29.

L. C. Harlan, A. L. Greene, L. X. Clegg, M. Mooney, J. L. Stevens, and M. L. Brown, “Insurance status and the use of guideline therapy in the treatment of selected cancers,” J Clin Oncol, 23, 36, 9079–9088, 2005, doi: https://doi.org/10.1200/JCO.2004.00.1297.CrossRefPubMed

30.

D. P. Cronin, L. C. Harlan, A. L. Potosky, L. X. Clegg, J. L. Stevens, and M. M. Mooney, “Patterns of care for adjuvant therapy in a random population-based sample of patients diagnosed with colorectal cancer,” Am J Gastroenterol, 101, 10, 2308–2318, 2006, doi: https://doi.org/10.1111/j.1572-0241.2006.00775.x.CrossRefPubMed

31.

M. E. Salem et al., “Impact of Sociodemographic Disparities and Insurance Status on Survival of Patients with Early-Onset Colorectal Cancer,” Oncologist, 26, 10, e1730–e1741, 2021, doi: https://doi.org/10.1002/onco.13908.CrossRefPubMedPubMedCentral

32.

N. Coburn, J. Fulton, D. N. Pearlman, C. Law, B. DiPaolo, and B. Cady, “Treatment variation by insurance status for breast cancer patients,” Breast J, 14, 2, 128–134, 2008, doi: https://doi.org/10.1111/j.1524-4741.2007.00542.x.CrossRefPubMed

33.

M.-C. Hsieh et al., “The effect of comorbidity on the use of adjuvant chemotherapy and type of regimen for curatively resected stage III colon cancer patients,” Cancer Med, 5, 5, 871–880, 2016, doi: https://doi.org/10.1002/cam4.632.CrossRefPubMedPubMedCentral

34.

N. L. Keating et al., “Adjuvant chemotherapy for stage III colon cancer: do physicians agree about the importance of patient age and comorbidity?,” J Clin Oncol, 26, 15, 2532–2537, 2008, doi: https://doi.org/10.1200/JCO.2007.15.9434.CrossRefPubMed

35.

I. H. Zuckerman et al., “Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer,” J Am Geriatr Soc, 57, 8, 1403–1410, 2009, doi: https://doi.org/10.1111/j.1532-5415.2009.02355.x.CrossRefPubMed

36.

C. J. Bradley, C. W. Given, B. Dahman, and T. L. Fitzgerald, “Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients with colon cancer,” Arch Intern Med, 168, 5, 521–529, 2008, doi: https://doi.org/10.1001/archinternmed.2007.82.CrossRefPubMed

37.

S. A. Dobie, J. L. Warren, B. Matthews, D. Schwartz, L.-M. Baldwin, and K. Billingsley, “Survival benefits and trends in use of adjuvant therapy among elderly stage II and III rectal cancer patients in the general population,” Cancer, 112, 4, 789–799, 2008, doi: https://doi.org/10.1002/cncr.23244.CrossRefPubMed

38.

S. A. Dobie, L.-M. Baldwin, J. A. Dominitz, B. Matthews, K. Billingsley, and W. Barlow, “Completion of therapy by Medicare patients with stage III colon cancer,” J Natl Cancer Inst, 98, 9, 610–619, 2006, doi: https://doi.org/10.1093/jnci/djj159.CrossRefPubMed

39.

V. E. P. P. Lemmens, A. H. van Halteren, M. L. G. Janssen-Heijnen, G. Vreugdenhil, O. J. Repelaer van Driel, and J. W. W. Coebergh, “Adjuvant treatment for elderly patients with stage III colon cancer in the southern Netherlands is affected by socioeconomic status, gender, and comorbidity,” Annals of Oncology, 16, 5, 767–772, 2005, doi: https://doi.org/10.1093/annonc/mdi159.CrossRefPubMed

Title: Adjuvant Chemotherapy Is Associated with Improved Survival for Stage III Colon Cancer When Initiated Beyond 8 Weeks
Authors: Fasih Ali Ahmed, MD
Victoria S. Wu, BA
Hanna Kakish, MD
Luke Rothermel, MD, MPH
Sharon L. Stein, MD
Emily Steinhagen, MD
Richard Hoehn, MD
Publication date: 20-06-2023
Publisher: Springer US
Keywords: Colon Cancer
Colon Cancer
Cytostatic Therapy
Colectomy
Colectomy
Published in: Journal of Gastrointestinal Surgery / Issue 9/2023
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-023-05748-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Adjuvant Chemotherapy Is Associated with Improved Survival for Stage III Colon Cancer When Initiated Beyond 8 Weeks

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2023

Distal Versus Total D2-Gastrectomy for Gastric Cancer: a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial

Esophageal Motility in Patients with Achalasia After Acupuncture

Utilization of Neoadjuvant Therapy in Gastrointestinal Stromal Tumors of the Stomach: Analysis of the 2006–2018 National Cancer Database

Pure Laparoscopic Donor Right Hepatectomy for Rare Non-Bifurcation Portal Vein Variation Donor and Reconstruction Technique

Dye-Less Perfusion Quantification of Porcine Gastric Conduit with Laser Speckle Contrast Imaging and Laser Doppler Imaging

Predictive Ability of Comorbidity Indices for Surgical Morbidity and Mortality: a Systematic Review and Meta-analysis