doi:10.1111/codi.13060
Original article
Time trends, improvements and national auditing of rectal cancer management over an 18-year period K. Kodeda*, R. Johansson†, N. Zar‡, H. Birgisson§, M. Dahlberg¶, S. Skullman**, G. Lindmark††, B. Glimelius‡‡, L. P ahlman§ and A. Martling§§ *Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, †Department of Radiation Sciences, Oncology, Ume a University, Ume a, Sweden, ‡Department of Surgery, Ryhov County Hospital, J€ onk€ oping, Sweden, §Department of Surgical Science, Uppsala University, Uppsala, Sweden, ¶Department of Surgery and Perioperative Sciences, Ume a University, Ume a, Sweden, **Department of Surgery, Skaraborg Hospital – Sk€ ovde, Sk€ ovde, Sweden, ††Department of Surgery, Helsingborg Hospital/Lund University, Helsingborg, Sweden, ‡‡Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden and §§Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Received 10 March 2015; accepted 11 May 2015; Accepted Article online 8 July 2015
Abstract Aim The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. Method Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. Results During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary
Introduction For the past decades there have been improvements in outcomes for patients with rectal cancer in many west€ Sahlgrenska University Correspondence to: Dr Karl Kodeda, Kirurgkliniken SU/O Hospital, S-416 85 G€ oteborg, Sweden. E-mail: [email protected] This paper has not been presented to a society or meeting. However, some figures and data have been presented and discussed at registry meetings in Swedish and at the national meeting of the Swedish Surgical Society in August 2014.
O168
team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. Conclusion There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference. Keywords Rectal neoplasms, registries, quality control, therapy, surgery What does this paper add to the literature? The study describes time trends in the management of patients with rectal cancer in Sweden. We discuss the possible impact of national auditing and make data from the past 18 years from the Swedish ColoRectal Cancer Registry publicly accessible for appraisal of external validity in selected patient series and for comparison with other cohorts. ern countries, but to what extent this can be attributed to auditing in quality control registries is unknown. Survival after rectal cancer treatment has improved, more advanced tumours are treated and also patients with distant metastases can in selected cases be offered the chance of cure. More dramatically, the rate of local recurrence after rectal cancer surgery has dropped from 30% to 40% to below 5% in some series [1–4]. This has been accredited to improved surgical technique, where the introduction of total mesorectal excision (TME) in the mid-1980s was fundamental, and to the use of
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
Rectal cancer management over an 18-year period
K. Kodeda et al.
preoperative (chemo)radiotherapy [5]. Adequate preoperative imaging and staging with magnetic resonance imaging are crucial for tailoring the treatment [6,7]. Also pathological examination of the operative specimen is important to evaluate radicality, provide feedback to radiologists and surgeons and to supply the basis for decisions concerning possible adjuvant therapy [8]. To give each patient the best available treatment plan, multidisciplinary team (MDT) conferences are today the standard of care in most specialized institutions, underlining the importance of close cooperation between surgeons, clinical oncologists, radiologists, pathologists, contact nurses and others [5,9]. Improvements in the results of treatment have been reported from individual centres and at a regional or national level in several countries. This is also true for Sweden, where TME principles were adopted in the late 1980s and structured TME workshops started in 1994 with the focus on improving rectal cancer surgery [10]. Several centres in the country either initiated or took part in some of the earliest randomized controlled trials on preoperative radiotherapy [5]. In Sweden, amongst some other countries, there is an ambition to improve the outcome not only in selected centres but also on a population-based level. National data are scrutinized by a steering group of the Swedish ColoRectal Cancer Registry (SCRCR) and are comparable with the best available institutional series. A yearly report from the registry is distributed to all operating units and made publicly accessible on the web. The report contains national data, including comparisons between healthcare regions and operating units. It contains comment from the steering group on any positive or alarming findings with reference to the recent international literature. Data are given for each operating unit based on 22 variables deemed of greatest importance for optimal cancer management. Each variable is presented in the form of a ‘point’ and the unit is given a score of 6 to 0 in relation to a predefined target. In many instances the targets are reached in agreement with relevant authorities. Of the 22 targets, 15 are process related such as lead time and proportion of patients discussed at an MDT conference or included in a clinical trial. The remaining seven targets are outcome-related surrogate end-points such as R0 resection, peri-operative bowel perforation, circumferential resection margin positivity or hard end-points such as local recurrence rate and postoperative mortality. This gives every unit a quick and easy overview on how well they are performing in relation to the national average and to previous years. The points and specific findings are presented and discussed by representatives from all hospitals at regional and national meetings, with the aim
that each unit should reduce deviation from the norm so the standard of care is equalized all over Sweden. Given that virtually every patient with rectal cancer has been included in the SCRCR since 1995, we aimed to explore time trends in the management and outcome of patients with rectal cancer in a national cohort over the subsequent 18 years. We also aimed to evaluate the possible impact of national auditing on variability between care providers and the overall outcome within the country. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series.
Method The Swedish Rectal Cancer Registry was launched in 1995 and has been described in detail elsewhere [11]. Since 2007 it was broadened to include patients with colon cancer, in part separately managed in the Swedish Colon Cancer Registry [12]. These two registries have now been merged and all data were amalgamated into one data set in 2013. Henceforth this registry will be referred to as the SCRCR, which covers more than 99% of patients diagnosed with invasive adenocarcinoma of the colon or rectum in Sweden (diagnoses at autopsy excluded) and is thus truly population based with minimal selection bias. It is extremely rare that patients do not consent to have their data recorded in the SCRCR. Vital statistics are retrieved from official demographic registries and only a minimal number of patients are not accounted for. Validation of data is crucial and efforts on validating the registry have been described elsewhere [11,13]. The present analysis follows the guidelines given by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [14] and is presented according to the uniform requirements of the International Committee of Medical Journal Editors [15]. This publication has been prepared by members of the national steering group of the SCRCR. The present analysis is based on data from the SCRCR on patients with rectal cancer diagnosed between 1995 and 2012. In order to evaluate time trends, the patients were separated into three different cohorts diagnosed during the 6-year periods of 1995– 2000, 2001–2006 and 2007–2012. Data on management, 30- and 90-day outcome and survival were analysed for all patients. The analysis of local recurrence was limited to patients with more than 3 years of follow-up. Statistical analysis
The v2 test was used for group comparisons and comparison of survival was analysed using the log-rank test.
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
O169
Rectal cancer management over an 18-year period
K. Kodeda et al.
The tests were two-sided and a P value of < 0.05 was considered statistically significant. Relative survival analyses were computed by using R Statistical Programming Language (R Foundation for Statistical Computing, Vienna, Austria), release 2.14.2, and the method of Hakulinen and Abeywickrama [16] was applied. Relative survival was calculated with reference to the survival rate in the national population standardized by gender, age and year. Date of death was retrieved from the Swedish Cause of Death Registry where only a small proportion of patients were censored owing to missing information, mainly as a result of emigration. STATA statistical software release 12 (StataCorp LP, College Station, Texas, USA) was used for data processing and all statistical analyses except for survival analyses.
Results A flow diagram on inclusion and follow-up of patients is shown in Fig. 1. Of 29 934 potentially eligible patients, nine were excluded leaving 29 925 for analysis. Exclusion was due to different definitions of the date of diagnosis in the SCRCR and the National Cancer Registry. Approximately 80% of patients had the tumour resected or excised. Although most data on these patients were possible to analyse, the followup period was too short in some analyses for patients operated in the past 3 and 5 years, respectively. Some 620 (3.2%) had inadequate 3-year follow-up and an additional 337 (2.1%) had inadequate 5-year follow-up.
Patients with rectal cancer in Sweden * n = 30 100 Not included in the SRCR n = 166 (0.6%)
Patients in the SRCR n = 29 934 Excluded from the present analysis n = 9 (0.0%) Patients analysed n = 29 925
Not resected nor excised n = 6 043 (20.2%) Patients where tumours were resected or excised † n = 23 882
Operated 2010-2012 n = 4 254
Inadequate 3 year follow-up n = 620 (3.2% of 19 628) Followed for 3 years ‡ n = 19 008 Operated 2008-2009 n = 2 651
Inadequate 5 year follow-up n = 337 (2.1% of 16 357) Followed for 5 years ‡ n = 16 020
O170
Figure 1 Modified flow diagram of inclusion and follow-up of patients. *Invasive adenocarcinoma of the rectum diagnosed in Sweden from 1995 through 2012 (diagnoses at autopsy excluded). † Anterior resection with anastomosis, Hartmann’s procedure, i.e. anterior resection with permanent colostomy without anastomosis, abdominoperineal resection, transanal endoscopic microsurgery or local excision. ‡Patients with inadequate follow-up include patients lost to follow-up (e.g. emigrated), patients reported too early (i.e. before 3 and 5 years postoperatively) and patients not reported to the registry. Patients with too short an interval between time of surgery and extraction of data from the registry are presented separately. Survival analyses are not affected by inadequate follow-up as date of death is extracted from official demographic registries.
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
Rectal cancer management over an 18-year period
K. Kodeda et al.
Table 1 shows the main clinical and histopathological characteristics of the patients in the three studied time periods. The number of patients increased in each 6-year period, but the age-adjusted incidence of rectal cancer was stable in the ageing population (data not shown). As demonstrated in Table 2, several changes in management occurred between the studied time periods. In all studied variables related to management the changes were constantly in the same direction between the first, second and third time periods. The proportion of patients who
did not have the tumour resected increased from 15.3% to 25.8%. Correspondingly, the proportion of patients where the resection was deemed curative increased and the proportion of palliative resections decreased. At the same time multi-organ resection increased from 9.9% to 16.6%. Figure 2a indicates a reduction in restorative resection in later years and this was most pronounced in the case of low-lying tumours (Table 2), where the proportion of anterior resection almost halved in preference to abdominoperineal resection.
Table 1 Patient and tumour characteristics in the three cohorts over time. 1995–2000
Total Gender Male Female Age (years) < 40 40–49 50–59 60–69 70–79 80–89 ≥ 90 Tumour stage* I II III IV Not resected or information missing Lower border of tumour† 0–5 cm > 5–10 cm > 10–15 cm Information missing Differentiation (grade)‡ Well (G1) Moderate (G2) Poor/undifferentiated (G3, G4) No tissue sample or information missing
2001–2006
2007–2012
Number of patients
Per cent
Number of patients
Per cent
Number of patientvs
Per cent
8676
29.0
9797
32.7
11 452
38.3
4927 3749
56.8 43.2
5702 4095
58.2 41.8
6754 4698
59.0 41.0
83 322 1059 2012 3166 1849 185
1.0 3.7 12.2 23.2 36.5 21.3 2.1
114 316 1267 2502 3144 2205 249
1.2 3.2 12.9 25.5 32.1 22.5 2.5
137 460 1443 3279 3544 2297 292
1.2 4.0 12.6 28.6 30.9 20.1 2.5
1780 2280 2216 1454 946
20.5 26.3 25.5 16.8 10.9
1961 2369 2494 1653 1320
20.0 24.2 25.5 16.9 13.5
2080 2294 2751 2259 2068
18.2 20.0 24.0 19.7 18.1
2777 3234 2477 188
32.0 37.3 28.6 2.2
3038 3949 2601 209
31.0 40.3 26.5 2.1
3532 4450 3190 280
30.8 38.9 27.9 2.4
575 4780 1120
6.6 55.1 12.9
341 3240 676
3.5 33.1 6.9
887 6565 1296
7.7 57.3 11.3
2201
25.4
5540
43.5
2704
23.6
P
0.008
< 0.001
< 0.001
0.001
< 0.001
Percentages may not add up to 100. *TNM, 7th edition from UICC/AJCC (Union for International Cancer Control/American Joint Committee on Cancer). Based on radiology and/or pathology report. †Measured in centimetres from the anal verge on retraction of a rigid rectosigmoidoscope in the left lateral position. ‡Histological grading for the years studied was reported on a scale of G1–G4, which today is dichotomized to low-grade (G1–G2) and high-grade (G3–G4).
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
O171
Rectal cancer management over an 18-year period
K. Kodeda et al.
Table 2 Management and outcome in the three cohorts over time. 1995–2000 Number of patients Total 8676 Operated 8094 Not operated 555 Information missing 27 Resected or excised* 7319 Not resected or excised 1330 Information missing 27 Followed-up 7243 3 years (1995–2009)* Lost to follow-up 21 Information missing 55 Followed-up 7177 5 years (1995–2007)* Lost to follow-up 25 Information missing 107 Of resected patients† 6766 Preoperative radiotherapy 3349 Preoperative radiotherapy alone 3278 Preoperative chemotherapy 71 and radiotherapy Preoperative chemotherapy alone 17 No preoperative oncological 3350 treatment Information missing on preoperative 50 treatment Curative intent 5585 Palliative intent 1108 Undetermined/unclear 27 Information missing 46 AR 4035 AR 0–6 cm 476 APR 2023 APR 0–6 cm 1755 Peri-tumoural peri-operative perforation 477 Rectal washout in AR 3166 Diverting stoma in AR (1998–2012) 681 Diverting stoma in AR < 10 cm 307 Resection of another organ 672 Laparoscopic resection (2003–2012) Converted (of laparoscopic) Information missing on conversion Anastomotic leak in AR (30 days postop) 370 Surgical complication (30 days postop) 1700 Reoperation (30 days postop) 698 Of patients where tumour was resected/excised* 30-day postop mortality 172 90-day postop mortality 341 Local recurrence at 3 years (1995–2009) 557
O172
2001–2006
2007–2012
Per cent
Number of patients
Per cent
Number of patients
Per cent
P
93.3 6.4 0.3 84.4 15.3 0.3 99.0
9797 8840 934 23 8064 1710 23 7802
90.2 9.5 0.2 82.3 17.5 0.2 96.8
11 452 9182 2270 0 8499 2953 0 3963
80.2 19.8 0.0 74.2 25.8 0.0 93.4
< 0.001
< 0.001
0.3 0.8 98.1
14 248 7580
0.2 3.1 94.0
11 271 1264
0.3 6.4 90.4
< 0.001
0.3 1.6
0.2 5.8 61.0 57.0 4.0
3 131 8100 5369 4040 1329
0.2 9.4
49.5 48.4 1.0
19 465 7530 4591 4293 298
66.3 49.9 16.4
< 0.001 < 0.001 < 0.001
0.3 49.5
34 2862
0.5 38.0
70 2657
0.9 32.8
< 0.001 < 0.001
0.7
43
0.6
4
0.0
82.5 16.4 0.4 0.7 59.6 19.6 29.9 72.3 7.0 78.5 33.0 47.0 9.9
9.2 25.1 10.3
6247 917 278 88 4119 442 2240 1914 439 3452 1733 838 1020 174 52 1 405 1980 759
83.0 12.2 3.7 1.2 54.7 16.6 29.7 71.9 5.8 83.8 42.1 58.5 13.5 3.4 29.9 0.0 9.8 26.3 10.1
7049 378 650 23 4055 312 2909 2372 419 3597 2987 1198 1346 542 121 3 354 1949 873
87.0 4.7 10.3 0.3 50.1 10.9 35.9 82.7 5.2 88.7 73.7 90.8 16.6 6.7 22.3 0.0 8.7 24.1 10.8
2.4 4.7 7.7
150 310 474
1.9 3.8 6.1
145 250 195
1.7 2.9 4.9
< 0.001
< 0.001 < 0.001 < 0.001 < < < < < < < < <
1 mm DRM>10 mm
10 0
0 2012
1995 Year
2012
1995 Year
Figure 2 Time trends in surgical and oncological management of patients with rectal cancer. (a) Proportion of different surgical procedures: AR, anterior resection with anastomosis; HA, Hartmann’s procedure, i.e. anterior resection with permanent colostomy without anastomosis; APR, abdominoperineal resection; TEM, transanal endoscopic microsurgery; LE, local excision; Ex Lap, explorative laparotomy without resection. (b) Proportion of patients treated with preoperative radiotherapy and chemotherapy respectively. As shown in Table 1 preoperative chemotherapy is predominantly administered as part of chemoradiation. (c) Median peri-operative blood loss in millilitres. Abbreviations as in (a). (d) Proportion of patients in relation to specific indicators of surgical quality: Perforation, peri-operative perforation of the bowel; Curative, surgical procedure deemed curative by operative surgeon; Washout, rectal washout beyond an occlusive clamp placed distally to the tumour before transection of the bowel; R0, microscopically radical resection; CRM, circumferential resection margin; DRM, distal resection margin. Some variables were introduced during the study period, explaining why some curves start after 1995. Part (a) is based on all analysed patients; parts (b)–(d) are based on patients operated with AR, HA and APR.
the presence of incurable distant metastases [17–20]. In addition, symptomatic patients without hope of cure can often be managed without resection. In imminent obstruction, minimally invasive measures can be used in order to decrease morbidity by means of laparoscopic sigmoidostomy or even stenting of tumours in the upper rectum. Pain can often be alleviated by palliative
O174
radiotherapy and bleeding might cease on chemotherapy and/or radiotherapy. There are patients, however, especially those with distant metastasis, for whom a locally radical tumour resection can be justified even in the presence of incurable disease. During the last 6 years,
Original article
Time trends, improvements and national auditing of rectal cancer management over an 18-year period K. Kodeda*, R. Johansson†, N. Zar‡, H. Birgisson§, M. Dahlberg¶, S. Skullman**, G. Lindmark††, B. Glimelius‡‡, L. P ahlman§ and A. Martling§§ *Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, †Department of Radiation Sciences, Oncology, Ume a University, Ume a, Sweden, ‡Department of Surgery, Ryhov County Hospital, J€ onk€ oping, Sweden, §Department of Surgical Science, Uppsala University, Uppsala, Sweden, ¶Department of Surgery and Perioperative Sciences, Ume a University, Ume a, Sweden, **Department of Surgery, Skaraborg Hospital – Sk€ ovde, Sk€ ovde, Sweden, ††Department of Surgery, Helsingborg Hospital/Lund University, Helsingborg, Sweden, ‡‡Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden and §§Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Received 10 March 2015; accepted 11 May 2015; Accepted Article online 8 July 2015
Abstract Aim The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. Method Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. Results During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary
Introduction For the past decades there have been improvements in outcomes for patients with rectal cancer in many west€ Sahlgrenska University Correspondence to: Dr Karl Kodeda, Kirurgkliniken SU/O Hospital, S-416 85 G€ oteborg, Sweden. E-mail: [email protected] This paper has not been presented to a society or meeting. However, some figures and data have been presented and discussed at registry meetings in Swedish and at the national meeting of the Swedish Surgical Society in August 2014.
O168
team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. Conclusion There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference. Keywords Rectal neoplasms, registries, quality control, therapy, surgery What does this paper add to the literature? The study describes time trends in the management of patients with rectal cancer in Sweden. We discuss the possible impact of national auditing and make data from the past 18 years from the Swedish ColoRectal Cancer Registry publicly accessible for appraisal of external validity in selected patient series and for comparison with other cohorts. ern countries, but to what extent this can be attributed to auditing in quality control registries is unknown. Survival after rectal cancer treatment has improved, more advanced tumours are treated and also patients with distant metastases can in selected cases be offered the chance of cure. More dramatically, the rate of local recurrence after rectal cancer surgery has dropped from 30% to 40% to below 5% in some series [1–4]. This has been accredited to improved surgical technique, where the introduction of total mesorectal excision (TME) in the mid-1980s was fundamental, and to the use of
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
Rectal cancer management over an 18-year period
K. Kodeda et al.
preoperative (chemo)radiotherapy [5]. Adequate preoperative imaging and staging with magnetic resonance imaging are crucial for tailoring the treatment [6,7]. Also pathological examination of the operative specimen is important to evaluate radicality, provide feedback to radiologists and surgeons and to supply the basis for decisions concerning possible adjuvant therapy [8]. To give each patient the best available treatment plan, multidisciplinary team (MDT) conferences are today the standard of care in most specialized institutions, underlining the importance of close cooperation between surgeons, clinical oncologists, radiologists, pathologists, contact nurses and others [5,9]. Improvements in the results of treatment have been reported from individual centres and at a regional or national level in several countries. This is also true for Sweden, where TME principles were adopted in the late 1980s and structured TME workshops started in 1994 with the focus on improving rectal cancer surgery [10]. Several centres in the country either initiated or took part in some of the earliest randomized controlled trials on preoperative radiotherapy [5]. In Sweden, amongst some other countries, there is an ambition to improve the outcome not only in selected centres but also on a population-based level. National data are scrutinized by a steering group of the Swedish ColoRectal Cancer Registry (SCRCR) and are comparable with the best available institutional series. A yearly report from the registry is distributed to all operating units and made publicly accessible on the web. The report contains national data, including comparisons between healthcare regions and operating units. It contains comment from the steering group on any positive or alarming findings with reference to the recent international literature. Data are given for each operating unit based on 22 variables deemed of greatest importance for optimal cancer management. Each variable is presented in the form of a ‘point’ and the unit is given a score of 6 to 0 in relation to a predefined target. In many instances the targets are reached in agreement with relevant authorities. Of the 22 targets, 15 are process related such as lead time and proportion of patients discussed at an MDT conference or included in a clinical trial. The remaining seven targets are outcome-related surrogate end-points such as R0 resection, peri-operative bowel perforation, circumferential resection margin positivity or hard end-points such as local recurrence rate and postoperative mortality. This gives every unit a quick and easy overview on how well they are performing in relation to the national average and to previous years. The points and specific findings are presented and discussed by representatives from all hospitals at regional and national meetings, with the aim
that each unit should reduce deviation from the norm so the standard of care is equalized all over Sweden. Given that virtually every patient with rectal cancer has been included in the SCRCR since 1995, we aimed to explore time trends in the management and outcome of patients with rectal cancer in a national cohort over the subsequent 18 years. We also aimed to evaluate the possible impact of national auditing on variability between care providers and the overall outcome within the country. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series.
Method The Swedish Rectal Cancer Registry was launched in 1995 and has been described in detail elsewhere [11]. Since 2007 it was broadened to include patients with colon cancer, in part separately managed in the Swedish Colon Cancer Registry [12]. These two registries have now been merged and all data were amalgamated into one data set in 2013. Henceforth this registry will be referred to as the SCRCR, which covers more than 99% of patients diagnosed with invasive adenocarcinoma of the colon or rectum in Sweden (diagnoses at autopsy excluded) and is thus truly population based with minimal selection bias. It is extremely rare that patients do not consent to have their data recorded in the SCRCR. Vital statistics are retrieved from official demographic registries and only a minimal number of patients are not accounted for. Validation of data is crucial and efforts on validating the registry have been described elsewhere [11,13]. The present analysis follows the guidelines given by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [14] and is presented according to the uniform requirements of the International Committee of Medical Journal Editors [15]. This publication has been prepared by members of the national steering group of the SCRCR. The present analysis is based on data from the SCRCR on patients with rectal cancer diagnosed between 1995 and 2012. In order to evaluate time trends, the patients were separated into three different cohorts diagnosed during the 6-year periods of 1995– 2000, 2001–2006 and 2007–2012. Data on management, 30- and 90-day outcome and survival were analysed for all patients. The analysis of local recurrence was limited to patients with more than 3 years of follow-up. Statistical analysis
The v2 test was used for group comparisons and comparison of survival was analysed using the log-rank test.
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
O169
Rectal cancer management over an 18-year period
K. Kodeda et al.
The tests were two-sided and a P value of < 0.05 was considered statistically significant. Relative survival analyses were computed by using R Statistical Programming Language (R Foundation for Statistical Computing, Vienna, Austria), release 2.14.2, and the method of Hakulinen and Abeywickrama [16] was applied. Relative survival was calculated with reference to the survival rate in the national population standardized by gender, age and year. Date of death was retrieved from the Swedish Cause of Death Registry where only a small proportion of patients were censored owing to missing information, mainly as a result of emigration. STATA statistical software release 12 (StataCorp LP, College Station, Texas, USA) was used for data processing and all statistical analyses except for survival analyses.
Results A flow diagram on inclusion and follow-up of patients is shown in Fig. 1. Of 29 934 potentially eligible patients, nine were excluded leaving 29 925 for analysis. Exclusion was due to different definitions of the date of diagnosis in the SCRCR and the National Cancer Registry. Approximately 80% of patients had the tumour resected or excised. Although most data on these patients were possible to analyse, the followup period was too short in some analyses for patients operated in the past 3 and 5 years, respectively. Some 620 (3.2%) had inadequate 3-year follow-up and an additional 337 (2.1%) had inadequate 5-year follow-up.
Patients with rectal cancer in Sweden * n = 30 100 Not included in the SRCR n = 166 (0.6%)
Patients in the SRCR n = 29 934 Excluded from the present analysis n = 9 (0.0%) Patients analysed n = 29 925
Not resected nor excised n = 6 043 (20.2%) Patients where tumours were resected or excised † n = 23 882
Operated 2010-2012 n = 4 254
Inadequate 3 year follow-up n = 620 (3.2% of 19 628) Followed for 3 years ‡ n = 19 008 Operated 2008-2009 n = 2 651
Inadequate 5 year follow-up n = 337 (2.1% of 16 357) Followed for 5 years ‡ n = 16 020
O170
Figure 1 Modified flow diagram of inclusion and follow-up of patients. *Invasive adenocarcinoma of the rectum diagnosed in Sweden from 1995 through 2012 (diagnoses at autopsy excluded). † Anterior resection with anastomosis, Hartmann’s procedure, i.e. anterior resection with permanent colostomy without anastomosis, abdominoperineal resection, transanal endoscopic microsurgery or local excision. ‡Patients with inadequate follow-up include patients lost to follow-up (e.g. emigrated), patients reported too early (i.e. before 3 and 5 years postoperatively) and patients not reported to the registry. Patients with too short an interval between time of surgery and extraction of data from the registry are presented separately. Survival analyses are not affected by inadequate follow-up as date of death is extracted from official demographic registries.
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
Rectal cancer management over an 18-year period
K. Kodeda et al.
Table 1 shows the main clinical and histopathological characteristics of the patients in the three studied time periods. The number of patients increased in each 6-year period, but the age-adjusted incidence of rectal cancer was stable in the ageing population (data not shown). As demonstrated in Table 2, several changes in management occurred between the studied time periods. In all studied variables related to management the changes were constantly in the same direction between the first, second and third time periods. The proportion of patients who
did not have the tumour resected increased from 15.3% to 25.8%. Correspondingly, the proportion of patients where the resection was deemed curative increased and the proportion of palliative resections decreased. At the same time multi-organ resection increased from 9.9% to 16.6%. Figure 2a indicates a reduction in restorative resection in later years and this was most pronounced in the case of low-lying tumours (Table 2), where the proportion of anterior resection almost halved in preference to abdominoperineal resection.
Table 1 Patient and tumour characteristics in the three cohorts over time. 1995–2000
Total Gender Male Female Age (years) < 40 40–49 50–59 60–69 70–79 80–89 ≥ 90 Tumour stage* I II III IV Not resected or information missing Lower border of tumour† 0–5 cm > 5–10 cm > 10–15 cm Information missing Differentiation (grade)‡ Well (G1) Moderate (G2) Poor/undifferentiated (G3, G4) No tissue sample or information missing
2001–2006
2007–2012
Number of patients
Per cent
Number of patients
Per cent
Number of patientvs
Per cent
8676
29.0
9797
32.7
11 452
38.3
4927 3749
56.8 43.2
5702 4095
58.2 41.8
6754 4698
59.0 41.0
83 322 1059 2012 3166 1849 185
1.0 3.7 12.2 23.2 36.5 21.3 2.1
114 316 1267 2502 3144 2205 249
1.2 3.2 12.9 25.5 32.1 22.5 2.5
137 460 1443 3279 3544 2297 292
1.2 4.0 12.6 28.6 30.9 20.1 2.5
1780 2280 2216 1454 946
20.5 26.3 25.5 16.8 10.9
1961 2369 2494 1653 1320
20.0 24.2 25.5 16.9 13.5
2080 2294 2751 2259 2068
18.2 20.0 24.0 19.7 18.1
2777 3234 2477 188
32.0 37.3 28.6 2.2
3038 3949 2601 209
31.0 40.3 26.5 2.1
3532 4450 3190 280
30.8 38.9 27.9 2.4
575 4780 1120
6.6 55.1 12.9
341 3240 676
3.5 33.1 6.9
887 6565 1296
7.7 57.3 11.3
2201
25.4
5540
43.5
2704
23.6
P
0.008
< 0.001
< 0.001
0.001
< 0.001
Percentages may not add up to 100. *TNM, 7th edition from UICC/AJCC (Union for International Cancer Control/American Joint Committee on Cancer). Based on radiology and/or pathology report. †Measured in centimetres from the anal verge on retraction of a rigid rectosigmoidoscope in the left lateral position. ‡Histological grading for the years studied was reported on a scale of G1–G4, which today is dichotomized to low-grade (G1–G2) and high-grade (G3–G4).
Colorectal Disease ª 2015 The Association of Coloproctology of Great Britain and Ireland. 17, O168–O179
O171
Rectal cancer management over an 18-year period
K. Kodeda et al.
Table 2 Management and outcome in the three cohorts over time. 1995–2000 Number of patients Total 8676 Operated 8094 Not operated 555 Information missing 27 Resected or excised* 7319 Not resected or excised 1330 Information missing 27 Followed-up 7243 3 years (1995–2009)* Lost to follow-up 21 Information missing 55 Followed-up 7177 5 years (1995–2007)* Lost to follow-up 25 Information missing 107 Of resected patients† 6766 Preoperative radiotherapy 3349 Preoperative radiotherapy alone 3278 Preoperative chemotherapy 71 and radiotherapy Preoperative chemotherapy alone 17 No preoperative oncological 3350 treatment Information missing on preoperative 50 treatment Curative intent 5585 Palliative intent 1108 Undetermined/unclear 27 Information missing 46 AR 4035 AR 0–6 cm 476 APR 2023 APR 0–6 cm 1755 Peri-tumoural peri-operative perforation 477 Rectal washout in AR 3166 Diverting stoma in AR (1998–2012) 681 Diverting stoma in AR < 10 cm 307 Resection of another organ 672 Laparoscopic resection (2003–2012) Converted (of laparoscopic) Information missing on conversion Anastomotic leak in AR (30 days postop) 370 Surgical complication (30 days postop) 1700 Reoperation (30 days postop) 698 Of patients where tumour was resected/excised* 30-day postop mortality 172 90-day postop mortality 341 Local recurrence at 3 years (1995–2009) 557
O172
2001–2006
2007–2012
Per cent
Number of patients
Per cent
Number of patients
Per cent
P
93.3 6.4 0.3 84.4 15.3 0.3 99.0
9797 8840 934 23 8064 1710 23 7802
90.2 9.5 0.2 82.3 17.5 0.2 96.8
11 452 9182 2270 0 8499 2953 0 3963
80.2 19.8 0.0 74.2 25.8 0.0 93.4
< 0.001
< 0.001
0.3 0.8 98.1
14 248 7580
0.2 3.1 94.0
11 271 1264
0.3 6.4 90.4
< 0.001
0.3 1.6
0.2 5.8 61.0 57.0 4.0
3 131 8100 5369 4040 1329
0.2 9.4
49.5 48.4 1.0
19 465 7530 4591 4293 298
66.3 49.9 16.4
< 0.001 < 0.001 < 0.001
0.3 49.5
34 2862
0.5 38.0
70 2657
0.9 32.8
< 0.001 < 0.001
0.7
43
0.6
4
0.0
82.5 16.4 0.4 0.7 59.6 19.6 29.9 72.3 7.0 78.5 33.0 47.0 9.9
9.2 25.1 10.3
6247 917 278 88 4119 442 2240 1914 439 3452 1733 838 1020 174 52 1 405 1980 759
83.0 12.2 3.7 1.2 54.7 16.6 29.7 71.9 5.8 83.8 42.1 58.5 13.5 3.4 29.9 0.0 9.8 26.3 10.1
7049 378 650 23 4055 312 2909 2372 419 3597 2987 1198 1346 542 121 3 354 1949 873
87.0 4.7 10.3 0.3 50.1 10.9 35.9 82.7 5.2 88.7 73.7 90.8 16.6 6.7 22.3 0.0 8.7 24.1 10.8
2.4 4.7 7.7
150 310 474
1.9 3.8 6.1
145 250 195
1.7 2.9 4.9
< 0.001
< 0.001 < 0.001 < 0.001 < < < < < < < < <
1 mm DRM>10 mm
10 0
0 2012
1995 Year
2012
1995 Year
Figure 2 Time trends in surgical and oncological management of patients with rectal cancer. (a) Proportion of different surgical procedures: AR, anterior resection with anastomosis; HA, Hartmann’s procedure, i.e. anterior resection with permanent colostomy without anastomosis; APR, abdominoperineal resection; TEM, transanal endoscopic microsurgery; LE, local excision; Ex Lap, explorative laparotomy without resection. (b) Proportion of patients treated with preoperative radiotherapy and chemotherapy respectively. As shown in Table 1 preoperative chemotherapy is predominantly administered as part of chemoradiation. (c) Median peri-operative blood loss in millilitres. Abbreviations as in (a). (d) Proportion of patients in relation to specific indicators of surgical quality: Perforation, peri-operative perforation of the bowel; Curative, surgical procedure deemed curative by operative surgeon; Washout, rectal washout beyond an occlusive clamp placed distally to the tumour before transection of the bowel; R0, microscopically radical resection; CRM, circumferential resection margin; DRM, distal resection margin. Some variables were introduced during the study period, explaining why some curves start after 1995. Part (a) is based on all analysed patients; parts (b)–(d) are based on patients operated with AR, HA and APR.
the presence of incurable distant metastases [17–20]. In addition, symptomatic patients without hope of cure can often be managed without resection. In imminent obstruction, minimally invasive measures can be used in order to decrease morbidity by means of laparoscopic sigmoidostomy or even stenting of tumours in the upper rectum. Pain can often be alleviated by palliative
O174
radiotherapy and bleeding might cease on chemotherapy and/or radiotherapy. There are patients, however, especially those with distant metastasis, for whom a locally radical tumour resection can be justified even in the presence of incurable disease. During the last 6 years,
