Screening vs. non-screening detected colorectal cancer: Differences in pre-therapeutic work up and treatment

Abstract

Objectives

To compare preoperative staging, multidisciplinary team-assessment, and treatment in patients with screening detected and non-screening detected colorectal cancer.

Methods

Data on patient and tumour characteristics, staging, multidisciplinary team-assessment and treatment in patients with screening and non-screening detected colorectal cancer from 2008 to 2012 were collected from the Stockholm–Gotland screening register and the Swedish Colorectal Cancer Registry.

Results

The screening group had a higher proportion of stage I disease (41 vs. 15%; p < 0.001), a more complete staging of primary tumour and metastases and were more frequently multidisciplinary team-assessed than the non-screening group (p < 0.001). In both groups, patients with endoscopically resected cancers were less completely staged and multidisciplinary team-assessed than patients with surgically resected cancers (p < 0.001). No statistically significant differences were observed between the screening and non-screening groups in the use of neoadjuvant treatment in rectal cancer (68 vs.76%), surgical treatment with local excision techniques in stage I rectal cancer (6 vs. 9%) or adjuvant chemotherapy in stages II and III disease (46 vs. 52%). Emergency interventions for colorectal cancer occurred in 4% of screening participants vs. 11% of non-compliers.

Conclusions

Screening detected cancer patients were staged and multidisciplinary team assessed more extensively than patients with non-screening detected cancers. Staging and multidisciplinary team assessment prior to endoscopic resection was less complete compared with surgical resection. Extensive surgical and (neo)adjuvant treatment was given in stage I disease. Participation in screening reduced the risk of emergency surgery for colorectal cancer.

Keywords

Colorectal cancer screening treatment staging multidisciplinary team

Introduction

Because screening programmes can identify patients with early stage disease, there is a risk that the reduction in mortality achieved by screening could come at the cost of over-treatment for some patients. It is important to ensure that patients with screening detected colorectal cancer (CRC) are neither over- nor under-treated. Thorough preoperative clinical staging (cTNM) should correctly identify early stage cancer (stage I), and guide selection and sequencing of treatment. Therapeutic alternatives should be evaluated in a multidisciplinary team (MDT) setting, to optimize treatment for the individual patient. For early CRC, therapeutic alternatives to major abdominal resection surgery include endoscopic resections techniques, such as endoscopic mucosal resection and endoscopic submucosal resection, and local excision techniques, including transanal endoscopic microsurgery (TEMS) with or without preoperative (chemo) radiotherapy.^1,2 A non-surgical strategy with chemo radiotherapy alone for distal rectal cancer has, in selected cases, given a complete response, leaving no residual tumour.³ For early rectal cancer patients scheduled for surgical treatment, the use of neoadjuvant therapy (i.e. radiotherapy) may not balance the benefit of reduced local recurrence rates and the negative side effects of increased morbidity and impaired function. This study aims to evaluate the completeness of preoperative staging and MDT-assessment, and the subsequent treatment of patients with population-based screening detected CRC compared with patients with non-screening detected CRC.

Methods

In the Stockholm/Gotland region (2.3 million inhabitants), population-based CRC screening began in 2008, progressively adding two birth cohorts every year until all of the target population had been included. Residents aged 60–69 were invited to biennial screening with guaiac-based faecal occult blood testing (FOBT) (Hemoccult®). Invitations were initiated centrally, without primary health care physician involvement. A test-kit with instructions was posted, and a reminder sent after 8 weeks if no results were registered. Patients with positive tests (at least one out of three cards) were immediately referred for colonoscopy and booked for examination within 2 weeks. CRC detection was followed by referral to one of the region’s nine surgical colorectal units.

Data were collected from the Stockholm–Gotland screening register and the Swedish Colorectal Cancer Registry. All data on the screening process, colonoscopy procedure and findings, including the histopathological diagnosis, were prospectively collected in the Stockholm–Gotland screening register (previously described⁴). The Swedish Colorectal Cancer Registry is a national quality register collecting data on all patients with adenocarcinomas in the colon and rectum. The registry started in 1995 including patients with rectal cancer, and in 2007 patients with colon cancer were added. Data are prospectively and continuously collected to ensure quality control and adherence to national guidelines, and are also used for research and clinical studies. Detailed information on preoperative clinical staging (cTNM), (neo) adjuvant treatment, the surgical procedure and findings, pathological staging (pTNM) according to the International Union Against Cancer/American Joint Committee on Cancer tumour node metastasis classification, complications according to the Clavien-Dindo classification and follow-up until 5 years after diagnosis are recorded.^5,6 The registry has a 98% coverage of all cases of CRC in Sweden,^7,8 collected data on rectal cancer has demonstrated a high validity,⁹ and validation of the colon cancer part of the registry is ongoing.¹⁰

Data on all individuals in the screening programme with a positive FOBT from 1 January 2008 to 31 December 2012 were retrieved. On all patients with a screening detected and histopathologically verified CRC, data regarding patient and tumour characteristics, preoperative work-up and treatment were further analysed.

Corresponding data were retrieved from the Swedish Colorectal Cancer Registry on all patients aged 60–69 with a histopathologically verified CRC diagnosed from 1 January 2008 to 31 December 2012. The group of patients with screening detected CRC was then excluded from this cohort to generate a control group of all patients with non-screening detected CRC in Sweden, matched by age to those with screening detected CRC.

Chi-square test and Fisher’s exact test were used as appropriate to determine significant differences between proportions. The p-values < 0.05 were considered statistically significant. Stata 12.0 (StataCorp, 4905 Lakeway Drive, Collage Station, TX 77845, USA) was used for the statistical analysis. The study was approved by the Regional Ethics Committee in Stockholm.

Results

During the study period, 205,842 individuals received at least one screening test kit. Of the 131,671 (64%) individuals who participated, 4618 had one positive (guaiac based) FOBT, and of these, 4080 (88%) complied with the assessment colonoscopy. The number of histopathologically confirmed screening detected CRCs was 249, yielding a cancer detection rate in screened individuals of 0.2%.

Pre-therapeutic assessment

Complete staging and MDT assessment is strongly advocated under national guidelines and is considered a quality indicator in the treatment of CRC patients. Specialists in surgery, oncology, pathology and radiology, as well as a contact nurse routinely attend the MDT conferences. Table 1 presents data on pre-therapeutic staging among screening and non-screening detected CRC in relation to delivered treatment. A higher proportion of patients with screening-detected cancers was assessed at an MDT conference and had a complete staging of the primary tumour, lung- and liver metastases, compared with the proportion with non-screening detected cancers (p < 0.001). Within both groups, patients with endoscopically resected cancers were preoperatively MDT-assessed and staged to lesser extent than patients with surgically resected cancers. This difference was statistically significant between the groups for preoperative MDT assessment, staging of primary tumour, lung and liver metastases (p < 0.001). Patients in the screening group had a higher proportion of colon cancers (p < 0.05) and a higher proportion of stage I disease compared with patients with non-screening detected cancers (p < 0.001) (Table 2).

Table 1.

Staging and multidisciplinary team (MDT)-assessment of patients with screening and non-screening detected colorectal cancer planned for elective surgery.

	Screening (n = 244) Surgical resection (n = 210) Endoscopic resection (n = 24) Non-resection (n = 10)	Non-screening^a (n = 6204) Surgical resection (n = 5054) Endoscopic resection (n = 194) Non-resection (n = 919)	Pearson χ²
Staging of primary tumour	(%)	(%)	p < 0.001
Surgical resection	198 (94)	4378 (87)
Endoscopic resection	11 (46)	46 (24)
Non-resection group	10 (100)	764 (83)
Staging of liver/lung metastases			p < 0.001
Surgical resection	206 (98)	4936 (98)
Endoscopic resection	12 (50)	49 (25)
Non-resection group	9 (90)	885 (96)
Preoperative MDT			p < 0.001
Surgical resection	188 (90)	3505 (69)
Endoscopic resection	6 (25)	31 (16)
Non-resection group	8 (80)	710 (77)
Postoperative MDT			p < 0.001
Surgical resection	197 (94)	3938 (78)
Endoscopic resection	19 (79)	81 (42)
Non-resection group	6 (60)	268 (29)

Thirty-seven cases not included in the analysis: missing (n = 12), unspecified operation (n = 16) and appendectomy (n = 9).

Table 2.

Baseline patient and tumour characteristics of all patients with screening detected vs. non-screening detected colorectal cancer diagnosed 2008–2012.

	Screening (n = 249) (%)	Non-screening (n = 7055) (%)	Pearson χ²
Gender			p = 0.05
Male	160 (64)	4092 (58)
Female	89 (36)	2963 (42)
Median age (years)	66	66
Tumour location			p < 0.05
Colon	179 (72)	4381 (62)
Rectum	70 (28)	2665 (38)
Missing	–	9 ( < 1)
Stage (cTNM)			p < 0.001
I	58 (23)	731 (10)
II	26 (10)	905 (13)
III	58 (23)	1179 (17)
IV	26 (10)	1543 (22)
Indeterminate or missing	81 (33)	2697 (38)
Stage (pTNM)			p < 0.001
I	102 (41)	1070 (15)
II	58 (23)	1711 (24)
III	58 (23)	1903 (27)
IV	26 (10)	1671 (24)
Indeterminate or missing	5 (2)	700 (10)

Treatment

Among patients with screening detected CRC, 244 (98%) underwent elective interventions (Figure 1). The majority, 210 patients (86%), underwent surgical resection; 24 patients (10%) underwent endoscopic resection. In 10 patients (4%), the decision following an MDT, or at laparotomy, was not to attempt of resection. Of the patients undergoing surgical resection, 209 (99.5%) underwent abdominal resection. The corresponding numbers among patients with non-screening detected cancers were 6204 (88%) underwent elective treatment, of whom 5054 (81%) underwent surgical resection; 4992 (99%) of these were abdominal resections. Endoscopic resection was performed on 194 (3%) patients and non-resectional therapy on 919 (15%) patients. The proportion of emergency interventions in CRC cases among those participating in screening was 4%, among individuals with a positive FOBT attending screening it was 2%, and among those with a negative FOBT attending screening it was 6%. Among those invited to, but not attending screening the proportion of emergency cases was 11%, and in those not invited to screening, 12% (p < 0.001).

Figure 1.

Overview of interventions in patients with screening and non-screening detected colorectal cancer.

Rectal cancer

In the screening group, 16 patients (23%) with electively treated rectal cancer had (cTNM) stage I disease, among whom one patient underwent endoscopic resection, and none was resected with TEMS or transanal excision. In the non-screening group, 369 patients with electively treated rectal cancer had (cTNM) stage I disease (14%), of whom 23 (6%) underwent TEMS or transanal excision. Endoscopic resection of the tumour was performed in 9 (2%) patients. There was no statistically significant difference between the groups in the use of local excision techniques, i.e. TEMS, transanal excision or endoscopic resection (p = 1.0).

(Neo)adjuvant therapy

Among patients with rectal cancer selected for abdominal surgery, the proportions assigned for neo adjuvant (chemo) radiotherapy were 68% and 76% in the screening and non-screening groups, respectively (p = 0.14) (Figure 2). In stage I (cTNM), 40% of patients in both groups were assigned for neo-adjuvant treatment. Adjuvant chemotherapy after elective abdominal resection surgery in patients with stages II and III (pTNM) CRC was given to 46% of patients in the screening group and 52% of patients in the non-screening group (p = 0.15).

Figure 2.

Neoadjuvant (chemo) radiotherapy in relation to stages I–IV(cTNM) in patients with screening detected (S) and non-screening detected (NS) rectal cancer prior to elective abdominal resection surgery.

Discussion

Patients in our study with screening detected CRC had a more complete preoperative staging of the primary tumour and distant metastases, had more early stage tumours, and underwent MDT assessment to a higher extent than the patients with non-screening detected CRC. No difference was seen between the groups in the use of abdominal resection surgery and (neo)adjuvant therapy. Screening participants were at low risk of emergency interventions.

MDT assessments are important for staging and planning of surgery, and also for the timing, sequencing and strategy of any (neo)adjuvant treatment. Studies have demonstrated that MDT conference assessment improves staging and survival and reduces involved resection margin.^11–13 The Swedish board of health and Welfare strongly advocates the use of MDT conferences for CRC patients.¹⁴ The high proportion of patients with complete staging and MDT-assessments in the screening group may reflect that these patients come from the Stockholm region, which has a higher completeness of staging and preoperative MDT-assessment in colon cancer patients than other Swedish regions.⁷ Restricting the comparison to the Stockholm region may eliminate these differences, but higher proportions of complete staging and MDT assessments are seen over time in all Swedish regions, thereby reducing regional differences.^7,8 In rectal cancer, the regional differences in staging and MDT-assessment are very small.⁸

The differences in staging and MDT assessment in patients treated with endoscopical resection compared with surgery were extensive. Although not desirable, the low rate of preoperative staging and MDT assessment is logical in a case of a polypectomy resulting in an unexpected cancer diagnosis. However, an endoscopic resection of a cancer-suspected lesion without a complete preoperative staging and MDT-assessment may be unsatisfactory management. With the introduction of new techniques (e.g. endoscopic mucosal and submucosal resection) as treatments, both for adenomas and as an option for early cancers, preoperative radiological staging and the MDT-assessment must be complete to ensure the correct selection of patients and tumours most suited to undergo resection.

The benefits of local excision for rectal cancer are recognized, in terms of low mortality, low morbidity and good functional results.^15,16 Limited use may be caused by concerns over local recurrence and impaired survival, although local recurrence rates following TEMS in small T1sm1 tumours (i.e. tumours extending to the most superficial third of the submucosal layer of the bowel wall) without adverse features are low,¹⁷ and 5-year overall survival is comparable with that using conventional radical surgery.^18,19 In this study, none of the patients with screening detected electively treated rectal cancer in (cTNM) stage I disease was treated with TEMS or transanal surgery, but in the non-screening group, the corresponding number was 23 out of 369 (6%). By comparison, 2010 data from the US National Cancer Database show that over 50% of patients with stage I rectal cancer were treated with local excision.²⁰ In attempting to avoid overtreatment of early stage cancer, this study suggests that there is potential to extend the use of local excision techniques, at least in rectal cancer, taking into consideration individual risk profile and patient preference.

In the present study, preoperative (chemo) radiotherapy was used extensively in rectal cancer patients from both the screening and non-screening detected groups; there was no statistically significant difference between the groups. Forty percent of patients with both screening detected and non-screening detected stage I rectal cancer underwent preoperative irradiation, a result in concordance with recent data on the extensive and increasing use of preoperative (chemo) radiotherapy in Stockholm.²¹ The side effects of irradiation, including impaired genito-urinary and bowel functions, increased risk of anastomotic leakage, and the risk of secondary pelvic insufficiency fractures, are well documented.^22–24 In this study, it was not possible to observe any possible benefit of reducing the use of pre-operative irradiation in patients with screening-detected early-stage rectal cancer.

Many studies have demonstrated that patients undergoing emergency surgery for CRC have more advanced tumours and a higher rate of obstruction and perforation at presentation. Previous studies have also shown that emergency surgery is associated with higher perioperative mortality, longer admissions, more readmissions, impaired disease-free survival and higher rates of loco regional recurrence.^25–27 In this study, there was a significant reduction of emergency interventions among individuals participating in screening (4% emergency interventions) compared with those not participating (11% emergency interventions), and those not invited to screening (12% emergency interventions). Similar observations have been made in England, where the introduction of CRC screening was followed by a reduction in the emergency surgery rate, falling to 12% in the screening age group compared with 16% overall.²⁸ In Scotland, a reduction of emergency admissions from 20% to 11% was observed in screening participants compared with controls.²⁹ Also in Scotland, a reduction from 20% to 13% of patients with emergency presentation of CRC prior to surgery was observed over time after the introduction of CRC screening.³⁰

The early detection benefits of screening will also have an impact on short- and long-term outcome by the reduction of emergency interventions.

Conclusion

Tumour staging and MDT-assessment were more complete in patients with screening detected compared with non-screening detected CRC. However, within both these groups, patients undergoing endoscopical resection were not staged and MDT was not assessed to the same extent as those treated with surgery. Overall, patients with early stage disease received extensive treatment, both in terms of surgery and (neo)adjuvant treatment. Screening participation reduced the risk of emergency surgery.

Footnotes

Acknowledgements

We thank Robert Johansson (MSc - Regional Cancer Centre North, Department of Radiation Science, Oncology, Umeå University, Sweden), Sini Kilpeläinen (Statistician, Regional Cancer Centre Stockholm–Gotland, Sweden) and Tongplaew Singnomklao (Data manager, Swedish Colorectal Cancer Registry, Regional Cancer Centre Stockholm–Gotland, Sweden) for their contributions in data extraction.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support was provided through the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm Community Council and Karolinska Institutet, and also by the Swedish Cancer Society and the Stockholm Cancer Society.

References

Repici

Hassan

De Paula Pessoa

. Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review. Endoscopy 2012; 44: 137–150.

Lezoche

Baldarelli

Lezoche

. Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg 2012; 99: 1211–1218.

Habr-Gama

Perez

Nadalin

. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004; 240: 711–717. discussion 7–8.

Blom

Kilpelainen

Hultcrantz

. Five-year experience of organized colorectal cancer screening in a Swedish population - increased compliance with age, female gender, and subsequent screening round. J Med Screen 2014; 21: 144–150.

Park

Choi

G-S

Hasegawa

. Validation of the seventh edition of the American Joint Committee on cancer tumor node-staging system in patients with colorectal carcinoma in comparison with sixth classification. J Surg Oncol 2012; 106: 674–679.

Dindo

Demartines

Clavien

. Classification of surgical complications - A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213.

Swedish Colorectal Cancer Registry. Colon cancer 2014, https://www.cancercentrum.se/globalassets/cancerdiagnoser/tjock–och-andtarm/kvalitetsregister/nationell-kvalitetsregisterrapport-tjocktarmscancer-2014.pdf (accessed 11 June 2016).

Swedish Colorectal Cancer Registry. Rectal cancer 2014, http://www.cancercentrum.se/globalassets/cancerdiagnoser/tjock–och-andtarm/kvalitetsregister/nationell-kvalitetsregisterrapport-andtarmscancer-2014.pdf (accessed 11 June 2016).

Pahlman

Bohe

Cedermark

. The Swedish rectal cancer registry. Br J Surg 2007; 94: 1285–1292.

10.

Kodeda

Nathanaelsson

Jung

. Population-based data from the Swedish Colon Cancer Registry. Br J Surg 2013; 100: 1100–1107.

11.

Burton

Brown

Daniels

. MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins? Br J Cancer 2006; 94: 351–357.

12.

Segelman

Singnomklao

Hellborg

. Differences in multidisciplinary team assessment and treatment between patients with stage IV colon and rectal cancer. Colorectal Dis 2009; 11: 768–774.

13.

Wright

De Vito

Langer

. Multidisciplinary cancer conferences: a systematic review and development of practice standards. Eur J Cancer 2007; 43: 1002–1010.

14.

Socialstyrelsen. The National Board of Health and Welfare. National guidelines for the treatment of breast, prostate and colorectal cancers, http://www.socialstyrelsen.se/Lists/Artikelkatalog/Attachments/19383/2014-4-2.pdf2014 (accessed 11 June 2016).

15.

De Graaf

Doornebosch

Tollenaar

. Transanal endoscopic microsurgery versus total mesorectal excision of T1 rectal adenocarcinomas with curative intention. Eur J Surg Oncol 2009; 35: 1280–1285.

16.

Doornebosch

Gosselink

Neijenhuis

. Impact of transanal endoscopic microsurgery on functional outcome and quality of life. Int J Colorectal Dis 2008; 23: 709–713.

17.

Bach

Hill

Monson

Simson

. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg 2009; 96: 280–290.

18.

Sgourakis

Lanitis

Gockel

. Transanal endoscopic microsurgery for T1 and T2 rectal cancers: a meta-analysis and meta-regression analysis of outcomes. Am Surg 2011; 77: 761–772.

19.

. TEM and conventional rectal surgery for T1 rectal cancer: a meta-analysis. Hepato-Gastroenterology 2011; 58: 364–368.

20.

Stitzenberg

Sanoff

Penn

. Practice patterns and long-term survival for early-stage rectal cancer. J Clin Oncol 2013; 31: 4276–4282.

21.

Elliot

Martling

Glimelius

. Preoperative treatment selection in rectal cancer: A population-based cohort study. Eur J Surg Oncol 2014; 40: 1782–1788.

22.

Marijnen

CAM

van de Velde

CJH

Putter

. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: Report of a multicenter randomized trial. J Clin Oncol 2005; 23: 1847–1858.

23.

Peeters

van de Velde

Leer

. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients–a Dutch colorectal cancer group study. J Clin Oncol 2005; 23: 6199–6206.

24.

Pommergaard

Gessler

Burcharth

. Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 2014; 16: 662–671.

25.

Amri

Bordeianou

Sylla

. Colon cancer surgery following emergency presentation: effects on admission and stage-adjusted outcomes. Am J Surg 2015; 209: 246–253.

26.

Bass

Fleming

Conneely

. Emergency first presentation of colorectal cancer predicts significantly poorer outcomes: a review of 356 consecutive Irish patients. Dis Colon Rectum 2009; 52: 678–684.

27.

Hogan

Samaha

Burke

. Emergency presenting colon cancer is an independent predictor of adverse disease-free survival. Int Surg 2015; 100: 77–86.

28.

Hwang

Evans

Lawrence

. Impact of bowel cancer screening on the management of colorectal cancer. Colorectal Dis 2014; 16: 450–458.

29.

Libby

Brewster

Steele

RJC

. Impact of faecal occult blood test screening on emergency admissions and short-term outcomes for colorectal cancer. Br J Surg 2014; 101: 1607–1615.

30.

Mansouri

McMillan

Crearie

. Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland. Br J Cancer 2015; 113: 556–561.