We currently do not know the optimal time interval between the end of chemoradiotherapy and surgery. Longer intervals have been associated with a higher pathological response rate, worse pathological outcomes and more morbidity. The aim of this study was to evaluate the effect and safety of the current trend of increasing time interval between the end of chemoradiotherapy and surgery (< 10 weeks vs. ≥ 10 weeks) on postoperative morbidity and pathological outcomes. This study analyzed 232 consecutive patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy from January 2012 to August 2018. 125 patients underwent surgery before 10 weeks from the end of chemoradiotherapy (Group 1) and 107 patients underwent surgery after 10 or more weeks after the end of chemoradiotherapy (Group 2). Results have shown that wait for ≥ 10 weeks did not compromise surgical safety. Pathological complete response and tumor stage was statistically significant among groups. The effect of wait for ≥ 10 weeks before surgery shown higher tumor regression than the first group (Group 1, 12.8% vs Group 2, 31.8%; p < 0.001). On multivariate analysis, wait for ≥ 10 weeks was associated with pathological compete response. Patients from the second group were four time more likely to achieve pathologic complete response than patients from the first group (OR, 4.27 95%CI 1.60–11.40; p = 0.004). Patients who undergo surgery after ≥ 10 weeks of the end of chemoradiotherapy are four time more likely to achieve complete tumor remission without compromise surgical safety or postoperative morbidity.
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Siegel R, Miller K, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Cli 68(1):7–30
de Campos-Lobato LF, Geisler DP, da Luz MA, Stocchi L, Dietz D, Kalady MF (2011) Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J Gastrointest Surg 15:444–450
Evans J, Tait D, Swift I, Pennert K, Tekkis P, Wotherspoon A, Chau I, Cunningham D, Brown G (2011) Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial? Dis Colon Rectum 54(10):1251–1259
Foster JD, Jones EL, Falk S, Cooper EJ, Francis NK (2011) Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature. Dis Colon Rectum 56(7):921–930
Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11(9):835–844
Glimelius B (2017) On a prolonged interval between rectal cancer (chemo)radiotherapy and surgery. Ups J Med Sci 122(1):1–10
Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M (2008) An interval %3e7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol 15:2661–2667
Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D (2017) Rectal cancer: ESMO clinical practice guidelines. Ann Oncol 28(suppl 4):iv22–iv40
Francois Y, Nemoz CJ, Baulieux J et al (1999) Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90–01 randomized trial. J Clin Oncol 17:2396
Supiot S, Bennouna J, Rio E et al (2006) Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer. Colorectal Dis 8:430–435
Wolthuis AM, Penninckx F, Haustermans K et al (2012) Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol 19(9):2833–2841
Mihmanlı M, Kabul Gürbulak E, Akgün İ et al (2016) Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer. World J Gastrointest Oncol 8(9):695–706
Petrelli F, Sgroi G, Sarti E, Barni S (2016) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg 263(3):458–464
Garcia-Aguilar J, Smith D, Avila K, Bergsland E, Chu P, Krieg R (2011) Optimal timing of surgery after chemoradiation for advanced rectal cancer. Ann Surg 254(1):97–102
Benson AB, Venook AP, Al-Hawary MM et al (2018) Rectal cancer, version 2.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 16:874–901. https://doi.org/10.6004/jnccn.2018.0061
Rombouts AJM, Hugen N, Elferink MAG, Nagtegaal ID, de Wilt JHW (2016) Treatment interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients: a population-based study. Ann Surg Oncol 23(11):3593–3601
Lefevre JH, Mineur L, Kotti S et al (2016) Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: a multicenter, randomized, controlled trial (GRECCAR-6). J Clin Oncol 34(31):3773–3780
Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Sezak M, Ozkok S, Kose T, Karabulut B, Harman M, Ozutemiz O (2018) Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg 105:1417–1425. https://doi.org/10.1002/bjs.10984
Jass JR, O’Brien J, Riddell RH, Snover DC (2008) Recommendations for the reporting of surgically resected specimens of colorectal carcinoma: association of directors of anatomic and surgical pathology. Am J Clin Pathol 129(1):13–23
Amin MB, Edge SB, Greene FL, et al. (eds) (2017) AJCC Cancer Staging Manual, 8th edn. Springer-Verlag, New York
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213
Ryan ÉJ, O'Sullivan DP, Kelly ME, Syed AZ, Neary PC, O'Connell PR, Kavanagh DO, Winter DC, O'Riordan JM (2019) Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer. Br J Surg 106:1298–1310. https://doi.org/10.1002/bjs.11220
Habr-Gama A, Perez R, Proscurshim I et al (2008) Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys 71(4):1181–1188
Tran CL, Udani S, Holt A, Arnell T, Kumar R, Stamos MJ (2006) Evaluation of safety of increased time interval between chemoradiation and resection for rectal cancer. Am J Surg 192:873–877
Sloothaak DA, van Leersum NJ, Punt CJ, Buskens CJ, Bemelman WA, Tanis PJ (2013) Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg 100(7):933–939
Researchers collaborating with the study: Dr. Núria Gómez Romeu, Dr. Júlia Gil, Dr. Anna Pigem, Dr. Ander Timoteo, Dr. Núria Ortega, Dr. Madalina Frunza.
There was no external financing to carry out the project.
Conflict of interest
There are no conflicts of interest to report.
Research involving human participants and/or animals
The study was approved by the Ethics Committee of University Hospital Dr. Josep Trueta (No 20817/2017).
As a retrospective analysis, informed consent was waived.
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Planellas Giné, P., Cornejo Fernández, L., Salvador Rosés, H. et al. Delaying surgery by more than 10 weeks after long-course neoadjuvant radiotherapy in locally advanced rectal cancer patients improves pathologic complete response . Updates Surg 72, 453–461 (2020). https://doi.org/10.1007/s13304-020-00747-0
- Rectal cancer
- Long course