Optimal Time Interval for Surgery After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer: Analysis of Health Insurance Review and Assessment Service Data

Min Jung Kim; Jin Suk Cho; Eun Mi Kim; Woo Ah Ko; Jae Hwan Oh

doi:10.3393/ac.2018.01.01

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Original Article Optimal Time Interval for Surgery After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer: Analysis of Health Insurance Review and Assessment Service Data: Min Jung Kim¹, Jin Suk Cho², Eun Mi Kim², Woo Ah Ko², Jae Hwan Oh¹; Annals of Coloproctology 2018;34(5):241-247.
DOI: https://doi.org/10.3393/ac.2018.01.01
Published online: October 31, 2018

¹Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea

²Health Insurance Review and Assessment Service, Seoul, Korea

Correspondence to: Jae Hwan Oh, M.D. Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel: +82-31-920-1505, Fax: +82-31-920-2798 E-mail: jayoh@ncc.re.kr

• Received: September 24, 2017 • Accepted: January 1, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
Acknowledgments
REFERENCES

See letter "Waiting and Hope: Optimal Time Interval for Surgery After Long-Course Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer" in Volume 34 on page 227.

Abstract

Purpose
Pathologic downstaging of rectal cancer has been suggested to be associated with the time interval from chemoradiotherapy (CRT) completion to surgery. We aimed to evaluate the effect of this time interval for patients with rectal cancer on the pathologic response.
Methods
All patients with rectal cancer undergoing neoadjuvant CRT with evaluable data were selected from among the Health Insurance Review and Assessment Service data. Patients were divided into groups according to the time between CRT and surgery. CRT responses were analyzed.
Results
Two hundred forty-nine patients were included, of whom 86 (34.5%) were in the 5- to 7-week interval, 113 (45.4%) in the 7- to 9-week interval, 38 (15.3%) in the 9- to 11-week interval, and 12 (4.8%) in the >11-week interval. The median time interval between CRT completion and surgery was 7.4 weeks (range: 5–22.7 weeks; interquartile range, 6.7–8.7 weeks). Surgery 9–11 weeks after CRT completion resulted in the highest, but not statistically significant, pathologic complete response (pCR) rate (3 patients, 8.6%; P = 0.886), no pCR was noted in the >11-week interval group. Results for downstaging in the 9- to 11-week interval group were as follows: T downstaging, 38.2% (P = 0.735); N downstaging, 50.0% (P = 0.439); and TN downstaging, 52.9% (P = 0.087). The 3-year overall survival rates for the 5- to 7-week, 7- to 9-week, 9- to 11-week, and >11-week interval groups were 93.0%, 85.0%, 81.6%, and 91.7%, respectively (P = 0.326).
Conclusion
Delaying surgery by 9 to 11 weeks may increase TN downstaging, but delaying for over 11 weeks may not increase additional tumor downstaging from long-course CRT.
Keywords: Neoadjuvant therapy; Rectal neoplasms

INTRODUCTION

Preoperative chemoradiotherapy (CRT) or radiotherapy has been the standard treatment for patients with advanced rectal cancer and reduces by about 50% the local recurrences in such patients compared to those who underwent surgery alone [1-4]. Preoperative CRT shrinks rectal cancers, and the degree of tumor response to radiotherapy relates to patients’ oncologic outcomes [5, 6], with patients with a higher pathologic tumor regression grade showing a higher disease-free survival. In the pooled analysis of 3,105 patients, the disease-free survival and the overall survival were higher, and the rates of local recurrence and distant metastasis were lower in patients with a pathologic complete response (pCR) than in those with residual tumors [7].

Shrinkage of the tumor and downstaging of the tumor are associated with the time from the completion of preoperative CRT to surgery [8-14]. To some point, CRT can shrink rectal cancer, but after some time point, the residual tumor regrows and results in tumor progression, except in 10%–20% of patients with a pCR. Several studies on the time intervals between preoperative CRT and surgery have been done, but the optimal time interval has not been established yet.

In 1999, the Lyon trial was a pivotal study in the current practice of 6- to 8-week intervals between preoperative CRT and surgery [8]. In that study, patients with a 0- to 2-week interval and those with a 6- to 8-week interval between preoperative CRT and surgery were compared. The longer interval group demonstrated a smaller pathologic remnant tumor and earlier tumor and nodal staging than the shorter interval group, but with no significant difference in long-term survival. That study compared only 2 groups, and the optimal time could not be defined. A nationwide cohort study from the Netherlands reported that the pCR rate and N downstaging were highest at 15 to 16 weeks from the initiation of radiotherapy, but the authors only reported pathologic outcomes without survival outcomes [14]. References about when to operate after preoperative radiotherapy in patients with locally advanced rectal cancers are lacking because previous studies have reported conflicting results, and most were retrospective studies performed at a single center [15-17]. Therefore, this study aimed to evaluate the effect of the time interval between completion of preoperative CRT and total mesorectal excision for patients with rectal cancer on the pathologic tumor response and patient’s survival by using data from a nationwide cohort database.

METHODS

Data source

This was a retrospective cohort study of the national database of the Health Insurance Review and Assessment Service (HIRA), South Korea. Since 2011, the HIRA has collected perioperative outcomes of patients with colorectal cancers to audit the standardized diagnosis and management and to improve the quality of treatment. The evaluation is conducted annually for all medical institutions in South Korea that treat patients with colorectal cancer. In the hospitals that have more than 100 new patients a year, 100 patients from each institution are randomly selected for the HIRA assessment whereas in the hospitals that have less than 100 patients per year, records of all patients are evaluated. The results of the quality assessment are given to each hospital and should be used to improve the quality of patient’s care. The items on the quality assessment are listed in Table 1. Colorectal cancer was coded as C18 (colon cancer), C19 (rectosigmoid colon cancer), or C20 (rectal cancer). Patients aged >18 years with primary colorectal cancer and those with synchronous colorectal cancer were included in the quality assessment. Patients with distant metastasis, other organ malignancies, and carcinomas in situ were excluded. This study was exempted from approval and informed consent from Institutional Review Board of National Cancer Center.

Patient selection

We selected patients from the HIRA database who had been diagnosed as having rectal cancer (C20) and had received preoperative long-course radiotherapy and then underwent surgery. Since 2012, the dates of radiotherapy and surgery have not been collected in the HIRA database; thus, only patients who underwent surgery between May 2011 and December 2011 were included in this study. The codes of the operations were QA921, Q2927, QA922, QA293, and QA924, which included anterior resection, low anterior resection with or without colonic pouch formation, abdominoperineal resection, and all operations such as a lymphadenectomy, respectively. We included cT2-4NxM0 stage cancers and histology with an adenocarcinoma or a mucinous adenocarcinoma. Patients with short-course preoperative radiotherapy, a history of colectomy, and lack of medical record information were excluded from this analysis.

Variables and definitions

Collected data included patient demographic characteristics, clinical and pathologic stages of the tumor, tumor location, treatment regimen, duration and completion date of neoadjuvant CRT, type of surgical procedure, completeness of the resection, and postoperative pathologic data. Patients were divided into 4 groups according to the time interval between the completion of preoperative radiotherapy and surgery: 5–7 weeks (35–48 days), 7–9 weeks (49–62 days), 9–11 weeks (63–6 days), and >11 weeks (>77 days). The primary outcome was the rate of pCR (ypT0N0), and secondary outcomes were tumor downstaging (ypT<cT), node downstaging (ypN<cN), TN downstaging (ypTN<cTN), and 3-year overall survival. Patients with ypT0-1 were defined as good responders to preoperative CRT. Overall survival was based on death due to any cause.

Statistical analyses

The chi-square test and the Fisher exact test were used for 4 group comparisons of categorical variables, as appropriate, and a 1-way analysis of variance was used for 4 group comparisons of continuous variables. The Kaplan-Meier method was used to estimate overall survival, and survival curves were compared among the four groups by using the log-rank test. A P-value <0.05 was considered statistically significant, and all statistical analyses were performed using SAS 9.3 (SAS Institute Inc., Cary, NC, USA).

RESULTS

Data of 1,920 patients who underwent operation for rectal cancer between May 2011 and December 2011 were collected from the HIRA database. We excluded 1,278 patients (66.6%) because they did not receive preoperative or postoperative radiotherapy (Fig. 1). Preoperative radiotherapy was performed in 436 of 642 (67.9%) patients. Additional patients were excluded from the analysis for the following reasons: (1) a lack of pathologic records (n = 178), (2) incomplete radiotherapy (n = 1), (3) operation after 560 days from the completion of radiotherapy (n = 1), and (4) an interval <4 weeks between the completion of radiotherapy and operation. Finally, 249 patients were included in the analysis.

The distribution of patients according to the time intervals between preoperative radiotherapy and operation is demonstrated in Fig. 2. Patients were classified into 4 groups based on the time interval between preoperative radiotherapy and operation: 5–7 weeks (n = 86), 7–9 weeks (n = 113), 9–11 weeks (n = 38), and >11 weeks (n = 12). The overall pCR rate was 16 of 249 (6.4%), and pCR was only observed in patients with an interval of 6–9 weeks. The baseline characteristics, sex, body mass index, and American Society of Anesthesiology physical status classification were not significantly different among the 4 groups (Table 2). The mean age was greater and incidence of a history of abdominal operation was higher in the >11-week interval group than in the other groups.

Pretreatment clinical stages are listed in Table 3. The cT classification, cN classification, and cTN classification were similar among the four groups (P = 0.19, P = 0.15, and P = 0.23, respectively). Most patients in all the groups had tumors of cT3 classification (5- to 7-week interval, 76.7%; 7- to 9-week interval, 77.9%; 9- to 11-week interval, 57.9%; and >11-week interval, 66.7%) and IIIb stage (5- to 7-week interval, 62.8%; 7- to 9-week interval, 63.7%; 9- to 11-week interval, 44.7%; and >11-week interval, 41.7%).

Postoperative outcomes are shown in Table 4. The median length of hospital stay was 13–14.5 days, and the difference was not significantly different among the 4 groups (P = 0.23). The numbers of harvested lymph nodes and tumor differentiation were similar among the groups according to the time interval between preoperative radiotherapy and operation. pCR rates were 6.2%, 7.6%, 8.6%, and 0% in the 5- to 7-week interval, 7- to 9-week interval, 9- to 11-week interval, and >11-week interval groups, respectively (P = 0.89). T downstaging, N downstaging, and TN downstaging were observed in 34.9%, 55.8%, and 57.4% of all patients, respectively, and T and N downstaging were not significantly different among the 4 groups. TN downstaging was observed in 64.5%, 69.2%, 52.9%, and 36.4% of patients in the 5- to 7-week interval, 7- to 9-week interval, 9- to 11-week interval, and >11-week interval groups, respectively (P = 0.09).

The median follow-up time was 39.7 ± 7.9 months. Three-year overall survival rates were 93.0%, 85.0%, 81.6%, and 91.7% in the 5- to 7-week interval, 7- to 9-week interval, 9- to 11-week interval, and >11-week interval groups, respectively (P = 0.33) (Fig. 3).

DISCUSSION

In this study, by using the HIRA database, we failed to define optimal timing for downstaging or pCR in patients with rectal cancer after preoperative CRT. The proportion of patients with TN downstaging was the highest in the 9- to 11-week interval, but this difference was not statistically significant. We could also not find a significant difference in the overall survival of patients according to the time interval between preoperative radiotherapy and surgery.

We used the nationwide HIRA database, which is used to evaluate the quality of treatment of patients with colorectal cancers. Comparing the time interval between preoperative radiotherapy and surgery at a single institution retrospectively would have been difficult because most patients undergo surgery within similar intervals according to surgeons’ preferences; however, in this nationwide study, we were able to collect data on a large number of patients with wide variations in that interval. Contrary to our expectation, since 2012, data on the quality control of the treatment of patients with colorectal cancers were collected without the dates of surgery and CRT so as to reduce the labor involved in data collection. Therefore, we could collect only data from the last half of 2011, which was the year in which quality control was evaluated nationally.

Many researchers have tried in prospective and several retrospective studies to identify the optimal time interval between preoperative radiotherapy and surgery to increase pCR rates and decrease operative morbidities, but the results have been conflicting and inconsistent [9-11, 15-21]. To the best of our knowledge, only 2 prospective studies have been performed on the time interval [8, 17]. Recently, a prospective clinical trial reported that waiting 11 weeks after CRT did not increase the rate of pCR after surgical resection [17]. Similar trends were also observed in the present study in that TN downstaging was most prominent in the 7- to 9-week interval group, and the downstaging rate decreased for longer intervals, although the differences were not statistically significant. With increasing preferences for the nonoperative management of patients with rectal cancers, presumptions exist that long intervals will increase the tumor response rate to CRT, but the results indicate that longer intervals do not convert nonresponders to good responders.

This study has several limitations. First, we designed the study to analyze the time intervals as continuous variables and to identify the optimal interval for increasing the pCR rate; however, we were unable to define the optimal interval due to a lack of data. If the HIRA database is to be used in future studies, more information, such as the dates of surgery and radiotherapy, is necessary. The number of patients was much smaller than we expected before initiating the study because the HIRA extracted 100 patients selectively from each institution and did not enroll all patients with rectal cancer, which made conducting statistical analyses with meaningful power and drawing definitive conclusions more difficult. Lastly, this database was set up only a few years ago; therefore, the present study had a follow-up period <4 years. Given that late recurrence is common in patients with rectal cancer treated with radiotherapy, this follow-up period might not be sufficient for evaluating oncologic outcomes, including the survival rate. In conclusion, delaying surgery by 9 to 11 weeks may increase TN downstaging, but delaying it for longer than 11 weeks may not lead to additional tumor downstaging from long-course CRT.

ARTICLE INFORMATION

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Acknowledgments

This study was supported by a grant from the Korean Society of Coloproctology.

Fig. 1.

Study flow chart.

Fig. 2.

Distribution of patients with rectal cancer according to the time interval between completion of preoperative chemoradiotherapy and surgery. Data are from the Health Insurance Review and Assessment Service. pCR, pathologic complete response.

Fig. 3.

Kaplan-Meier curves of overall survival for patients with rectal cancer according to the time interval between completion of preoperative chemoradiotherapy and surgery.

Table 1.

Evaluation index for quality assessment of colorectal cancer treatment by Health Insurance Review and Assessment (2011)

Sector	Division	Evaluation index
Structure (1)	Treatment coping power	1. Professional workforce composition
Procedure (19)	Diagnostic evaluation and recording completeness	2. Preoperative pain rating
		3. Confirmation rate of family history of colorectal cancer
		4. Percentage of preoperative surveillance
		5. Recording rate of completeness of assessment of resection
		6. Percentage of evaluations of postoperative carcinoembryonic antigen within three months after surgery
		7. Record fulfillment rate of pathology report
		8. Twelve or more local lymph nodes dissected and examination rate
		9. Recording rate of cancer stage by surgeon
		10. Recording rate of cancer stage by chemotherapy oncologist
		11. Recording rate of cancer stage by radiological oncologist
	Patient education	12. Rate of stoma care education
	Chemotherapy	13. Percentage of patients without chemotherapy (Stage I [or IIa])
		14. Percentage of chemotherapy administrations within eight weeks after surgery
		15. Rate of patients who were described with a chemotherapy plan
		16. Rate of flow sheet usage
		17. Rate of recommended chemotherapy administration
		18. Rate of patients who received antiemetics
	Radiotherapy	19. Administration rate of postoperative radiotherapy (rectal cancer)
		20. Administration rate of concurrent chemoradiotherapy (rectal cancer)
Result (3)	-	21. Average days of hospitalization (including postoperative hospitalization)
		22. Average inpatient treatment fee
		23. Operative mortality (mortality in hospital and postoperative 30-day mortality)

Table 2.

Baseline characteristics

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Age (yr)^*	61.2 ± 12^a	59.6 ± 11.5^a	61.2 ± 9.5^a	69.3 ± 7.9^b	0.04
Male sex	62 (72.1)	73 (64.6)	25 (65.8)	7 (58.3)	0.61
BMI (kg/m²)	23.4 ± 3.6	23.6 ± 3.1	23.9 ± 2.8	23.3 ± 3.8	0.86
Previous history of abdominal surgery^*	9 (10.5)^a	21 (18.6)^a	6 (15.8)^a	5 (41.7)^b	0.01
ASA PS classification					0.39
I	24 (27.9)	35 (31.0)	8 (21.1)	1 (8.3)
II	56 (65.1)	73 (64.6)	27 (71.1)	9 (75.0)
III	6 (7.0)	5 (4.4)	3 (7.9)	2 (16.7)

Values are presented as mean ± standard deviation or number (%).

RT, radiotherapy; BMI, body mass index; ASA PS, American Society of anesthesiologist physical status.

^*The results of post hoc comparisons were demonstrated as letters, a and b, and the same letters indicate a nonsignificant difference between the groups based on Tukey multiple comparison test using ranks or chi-square tests as appropriate.

Table 3.

Pretreatment clinical stage

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Clinical T classification					0.19
1/2	9 (10.5)	9 (8.0)	4 (10.5)	1 (8.3)
3	66 (76.7)	88 (77.9)	22 (57.9)	8 (66.7)
4a	4 (4.7)	11 (9.7)	7 (18.4)	2 (16.7)
4b	3 (3.5)	1 (0.9)	1 (2.6)	1 (8.3)
Clinical N classification					0.15
0	12 (14.0)	21 (18.6)	7 (18.4)	4 (33.3)
1	29 (33.7)	52 (46.0)	12 (31.6)	2 (16.7)
2a	32 (37.2)	30 (26.5)	11 (28.9)	6 (50.0)
2b	7 (8.1)	4 (3.5)	4 (10.5)	0 (0)
Clinical TN classification					0.23
I	3 (3.5)	4 (3.5)	0 (0)	1 (8.3)
IIA	9 (10.5)	15 (13.3)	5 (13.2)	3 (25.0)
IIB	0 (0)	2 (1.8)	2 (5.3)	0 (0)
IIIA	4 (4.7)	3 (2.7)	3 (7.9)	0 (0)
IIIB	54 (62.8)	72 (63.7)	17 (44.7)	5 (41.7)
IIIC	10 (11.6)	11 (9.7)	7 (18.4)	3 (25.0)

Values are presented as number (%).

RT, radiotherapy.

Table 4.

Postoperative data

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Length of hospital stay (day)	13.0 (8–112)	13.0 (7–39)	14.5 (8–39)	13.5 (10–21)	0.23
No. of harvested LNs (%)					0.63
<12	27 (31.4)	43 (38.1)	16 (42.1)	5 (41.7)
≥12	59 (68.6)	70 (61.9)	22 (57.9)	7 (58.3)
Tumor differentiation					0.42
High	14 (16.3)	18 (15.9)	4 (10.5)	3 (25.0)
Moderate	52 (60.5)	62 (54.9)	21 (55.3)	8 (66.7)
Low	4 (4.7)	1 (0.9)	1 (2.6)	0 (0)
Others	16 (18.6)	32 (28.3)	12 (31.6)	1 (8.3)
pCR (ypT0N0)	5 (5.8)	8 (7.1)	3 (7.9)	0 (0)	0.89
ypT0-1 (good responders)	9 (10.5)	14 (12.4)	4 (10.5)	1 (8.3)	0.99
Tumor response
T downstaging (ypT < cT)	26 (30.2)	44 (38.9)	13 (34.2)	4 (33.3)	0.74
N downstaging (ypN < cN)	52 (60.5)	64 (56.6)	17 (44.7)	6 (50.0)	0.44
TN downstaging (ypTN < cTN)	49 (57.0)	72 (63.7)	18 (47.4)	4 (33.3)	0.09

Values are presented as median (range) or number (%).

RT, radiotherapy; LN, lymph node; pCR, pathologic complete remission.

REFERENCES

1. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–46.Article PubMed
2. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012;30:1926–33.Article PubMed
3. van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12:575–82.Article PubMed
4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–40.Article PubMed
5. Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005;23:8688–96.Article PubMed
6. Yeo SG, Kim DY, Park JW, Choi HS, Oh JH, Kim SY, et al. Stageto-stage comparison of preoperative and postoperative chemoradiotherapy for T3 mid or distal rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:856–62.Article PubMed
7. Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010;11:835–44.Article PubMed
8. Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. 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 1999;17:2396. Article PubMed
9. Moore HG, Gittleman AE, Minsky BD, Wong D, Paty PB, Weiser M, et al. Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum 2004;47:279–86.Article PubMed
10. Habr-Gama A, Perez RO, Proscurshim I, Nunes Dos Santos RM, Kiss D, Gama-Rodrigues J, et al. 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 2008;71:1181–8.Article PubMed
11. Kerr SF, Norton S, Glynne-Jones R. Delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer may reduce postoperative morbidity without compromising prognosis. Br J Surg 2008;95:1534–40.Article PubMed
12. Jeong DH, Lee HB, Hur H, Min BS, Baik SH, Kim NK. Optimal timing of surgery after neoadjuvant chemoradiation therapy in locally advanced rectal cancer. J Korean Surg Soc 2013;84:338–45.Article PubMed PMC
13. Zeng WG, Zhou ZX, Liang JW, Wang Z, Hou HR, Zhou HT, et al. Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome. J Surg Oncol 2014;110:463–7.Article PubMed
14. Probst CP, Becerra AZ, Aquina CT, Tejani MA, Wexner SD, Garcia-Aguilar J, et al. Extended intervals after neoadjuvant therapy in locally advanced rectal cancer: the key to improved tumor response and potential organ preservation. J Am Coll Surg 2015;221:430–40.Article PubMed PMC
15. Lim SB, Choi HS, Jeong SY, Kim DY, Jung KH, Hong YS, et al. Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg 2008;248:243–51.Article PubMed
16. Dolinsky CM, Mahmoud NN, Mick R, Sun W, Whittington RW, Solin LJ, et al. Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer. J Surg Oncol 2007;96:207–12.Article PubMed
17. Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, et al. 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 2016;34:3773–80.Article PubMed
18. Tran CL, Udani S, Holt A, Arnell T, Kumar R, Stamos MJ. Evaluation of safety of increased time interval between chemoradiation and resection for rectal cancer. Am J Surg 2006;192:873–7.Article PubMed
19. Supiot S, Bennouna J, Rio E, Meurette G, Bardet E, Buecher B, et al. Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer. Colorectal Dis 2006;8:430–5.Article PubMed
20. Coucke PA, Notter M, Matter M, Fasolini F, Calmes JM, Schlumpf R, et al. Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): is it a matter of days? Acta Oncol 2006;45:1086–93.Article PubMed
21. Glehen O, Chapet O, Adham M, Nemoz JC, Gerard JP; Lyons Oncology Group. Long-term results of the Lyons R90-01 randomized trial of preoperative radiotherapy with delayed surgery and its effect on sphincter-saving surgery in rectal cancer. Br J Surg 2003;90:996–8.Article PubMed

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References

Citations

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Optimal Time Interval for Surgery After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer: Analysis of Health Insurance Review and Assessment Service Data

Ann Coloproctol. 2018;34(5):241-247. Published online October 31, 2018

DOI: https://doi.org/10.3393/ac.2018.01.01

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Optimal Time Interval for Surgery After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer: Analysis of Health Insurance Review and Assessment Service Data

Fig. 1. Study flow chart.

Fig. 2. Distribution of patients with rectal cancer according to the time interval between completion of preoperative chemoradiotherapy and surgery. Data are from the Health Insurance Review and Assessment Service. pCR, pathologic complete response.

Fig. 3. Kaplan-Meier curves of overall survival for patients with rectal cancer according to the time interval between completion of preoperative chemoradiotherapy and surgery.

Fig. 1.

Fig. 2.

Fig. 3.

Optimal Time Interval for Surgery After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer: Analysis of Health Insurance Review and Assessment Service Data

Sector	Division	Evaluation index
Structure (1)	Treatment coping power	1. Professional workforce composition
Procedure (19)	Diagnostic evaluation and recording completeness	2. Preoperative pain rating
		3. Confirmation rate of family history of colorectal cancer
		4. Percentage of preoperative surveillance
		5. Recording rate of completeness of assessment of resection
		6. Percentage of evaluations of postoperative carcinoembryonic antigen within three months after surgery
		7. Record fulfillment rate of pathology report
		8. Twelve or more local lymph nodes dissected and examination rate
		9. Recording rate of cancer stage by surgeon
		10. Recording rate of cancer stage by chemotherapy oncologist
		11. Recording rate of cancer stage by radiological oncologist
	Patient education	12. Rate of stoma care education
	Chemotherapy	13. Percentage of patients without chemotherapy (Stage I [or IIa])
		14. Percentage of chemotherapy administrations within eight weeks after surgery
		15. Rate of patients who were described with a chemotherapy plan
		16. Rate of flow sheet usage
		17. Rate of recommended chemotherapy administration
		18. Rate of patients who received antiemetics
	Radiotherapy	19. Administration rate of postoperative radiotherapy (rectal cancer)
		20. Administration rate of concurrent chemoradiotherapy (rectal cancer)
Result (3)	-	21. Average days of hospitalization (including postoperative hospitalization)
		22. Average inpatient treatment fee
		23. Operative mortality (mortality in hospital and postoperative 30-day mortality)

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Age (yr)^*	61.2 ± 12^a	59.6 ± 11.5^a	61.2 ± 9.5^a	69.3 ± 7.9^b	0.04
Male sex	62 (72.1)	73 (64.6)	25 (65.8)	7 (58.3)	0.61
BMI (kg/m²)	23.4 ± 3.6	23.6 ± 3.1	23.9 ± 2.8	23.3 ± 3.8	0.86
Previous history of abdominal surgery^*	9 (10.5)^a	21 (18.6)^a	6 (15.8)^a	5 (41.7)^b	0.01
ASA PS classification					0.39
I	24 (27.9)	35 (31.0)	8 (21.1)	1 (8.3)
II	56 (65.1)	73 (64.6)	27 (71.1)	9 (75.0)
III	6 (7.0)	5 (4.4)	3 (7.9)	2 (16.7)

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Clinical T classification					0.19
1/2	9 (10.5)	9 (8.0)	4 (10.5)	1 (8.3)
3	66 (76.7)	88 (77.9)	22 (57.9)	8 (66.7)
4a	4 (4.7)	11 (9.7)	7 (18.4)	2 (16.7)
4b	3 (3.5)	1 (0.9)	1 (2.6)	1 (8.3)
Clinical N classification					0.15
0	12 (14.0)	21 (18.6)	7 (18.4)	4 (33.3)
1	29 (33.7)	52 (46.0)	12 (31.6)	2 (16.7)
2a	32 (37.2)	30 (26.5)	11 (28.9)	6 (50.0)
2b	7 (8.1)	4 (3.5)	4 (10.5)	0 (0)
Clinical TN classification					0.23
I	3 (3.5)	4 (3.5)	0 (0)	1 (8.3)
IIA	9 (10.5)	15 (13.3)	5 (13.2)	3 (25.0)
IIB	0 (0)	2 (1.8)	2 (5.3)	0 (0)
IIIA	4 (4.7)	3 (2.7)	3 (7.9)	0 (0)
IIIB	54 (62.8)	72 (63.7)	17 (44.7)	5 (41.7)
IIIC	10 (11.6)	11 (9.7)	7 (18.4)	3 (25.0)

Variable	RT-surgery interval (wk) group				P-value
Variable	5–7 (n = 86)	7–9 (n = 113)	9–11 (n = 38)	≥11 (n = 12)	P-value
Length of hospital stay (day)	13.0 (8–112)	13.0 (7–39)	14.5 (8–39)	13.5 (10–21)	0.23
No. of harvested LNs (%)					0.63
<12	27 (31.4)	43 (38.1)	16 (42.1)	5 (41.7)
≥12	59 (68.6)	70 (61.9)	22 (57.9)	7 (58.3)
Tumor differentiation					0.42
High	14 (16.3)	18 (15.9)	4 (10.5)	3 (25.0)
Moderate	52 (60.5)	62 (54.9)	21 (55.3)	8 (66.7)
Low	4 (4.7)	1 (0.9)	1 (2.6)	0 (0)
Others	16 (18.6)	32 (28.3)	12 (31.6)	1 (8.3)
pCR (ypT0N0)	5 (5.8)	8 (7.1)	3 (7.9)	0 (0)	0.89
ypT0-1 (good responders)	9 (10.5)	14 (12.4)	4 (10.5)	1 (8.3)	0.99
Tumor response
T downstaging (ypT < cT)	26 (30.2)	44 (38.9)	13 (34.2)	4 (33.3)	0.74
N downstaging (ypN < cN)	52 (60.5)	64 (56.6)	17 (44.7)	6 (50.0)	0.44
TN downstaging (ypTN < cTN)	49 (57.0)	72 (63.7)	18 (47.4)	4 (33.3)	0.09

Table 1. Evaluation index for quality assessment of colorectal cancer treatment by Health Insurance Review and Assessment (2011)

Table 2. Baseline characteristics

Values are presented as mean ± standard deviation or number (%).

RT, radiotherapy; BMI, body mass index; ASA PS, American Society of anesthesiologist physical status.

The results of post hoc comparisons were demonstrated as letters, a and b, and the same letters indicate a nonsignificant difference between the groups based on Tukey multiple comparison test using ranks or chi-square tests as appropriate.

Table 3. Pretreatment clinical stage

Values are presented as number (%).

RT, radiotherapy.

Table 4. Postoperative data

Values are presented as median (range) or number (%).

RT, radiotherapy; LN, lymph node; pCR, pathologic complete remission.