Oncological Outcomes After TotalMesorectal Excision for Cure for Cancerof the Lower Rectum: Anterior vs.

Abdominoperineal ResectionArne Wibe, M.D.,1 Astri Syse, M.Sc.,2 Elisabeth Andersen, M.Sc.,2

Steinar Tretli, M.Sc., Ph.D.,2 Helge E. Myrvold, M.D., Ph.D.,1 Odd Søreide, F.R.C.S.,3

on behalf of the Norwegian Rectal Cancer Group1 Department of Surgery, St. Olavs Hospital, Trondheim, Norway2 The Cancer Registry of Norway, Oslo, Norway3 Centre for Health Technology Assessment, SINTEF Unimed, Oslo, Norway

PURPOSE: This study was designed to examine the outcomeof cancer of the lower rectum, particularly the rates of localrecurrence and survival for tumors located in this area thathave been treated by anterior or abdominoperineal resec-tions. METHODS: A prospective, observational, national, co-hort study which is part of the Norwegian Rectal CancerProject. The present cohort includes all patients undergoingtotal mesorectal excision in 47 hospitals during the periodNovember 1993 to December 1999. A total of 2,136 pa-tients with rectal cancer within 12 cm of the anal vergewere analyzed; there were 1,315 (62 percent) anterior re-sections and 821 (38 percent) abdominoperineal resections.The lower edge of the tumor was located 0 to 5 cm from theanal verge in 791 patients, 6 to 8 cm in 558 patients, and 9to 12 cm in 787 patients. According to the TNM classifica-tion, there were 33 percent Stage I, 35 percent Stage II, and32 percent Stage III. RESULTS: Univariate analyses: Thefive-year local recurrence rate was 15 percent in the lower

level, 13 percent in the intermediate level, and 9 percent inthe upper level (P = 0.014). It was 10 percent local recur-rence after anterior resection and 15 percent after abdomi-noperineal resection (P = 0.008). The five-year survival ratewas 59 percent in the lower level, 62 percent in the inter-mediate level, and 69 percent in the upper level (P < 0.001),respectively, and it was 68 percent in the anterior-resectiongroup and 55 percent in the abdominoperineal-resectiongroup (P < 0.001). Multivariate analyses: The level of thetumor influenced the risk of local recurrence (hazard ratio,1.8; 95 percent confidence interval, 1.1–2.3), but the op-erative procedure, anterior resection vs. abdominoperinealresection, did not (hazard ratio, 1.2; 95 percent confidenceinterval, 0.7–1.8). On the contrary, operative procedure in-fluenced survival (hazard ratio, 1.3; 95 percent confidenceinterval, 1–1.6), but tumor level did not (hazard ratio, 1.1;95 percent confidence interval, 0.9–1.5). In addition to pa-tient and tumor characteristics (T4 tumors), intraoperativebowel perforation and tumor involvement of the circumfer-ential margin were identified as significant prognostic fac-tors, which were more common in the lower rectum, ex-plaining the inferior prognosis for tumors in this region.CONCLUSIONS: T4 tumors, R1 resections, and/or intraop-erative perforation of the tumor or bowel wall are mainfeatures of low rectal cancers, causing inferior oncologicoutcomes for tumors in this area. If surgery is optimized,preventing intraoperative perforation and involvement ofthe circumferential resection margin, the prognosis for can-cers of the lower rectum seems not to be inherently differ-ent from that for tumors at higher levels. In that case, thelevel of the tumor or the type of resection will not be indi-cators for selecting patients for radiotherapy. [Key words:Low rectal cancer; Local recurrence; Survival]

From the Norwegian Gastrointestinal Cancer Group and the Nor-wegian Rectal Cancer Project. Members of The Norwegian Gastro-intestinal Cancer Group are listed in Appendix 1.

Read at the meeting of The American Society of Colon and RectalSurgeons, New Orleans, Louisiana, June 21 to 26, 2003.

Supported by a grant from the Norwegian Cancer Society.

Correspondence to: Arne Wibe, M.D., Department of Surgery, St.Olavs Hospita l , Trondheim, N-7006, Norway, e-mai l :arne.wibe@medisin.ntnu.no

Dis Colon Rectum 2004; 47: 48–58DOI: 10.1007/s10350-003-0012-y© The American Society of Colon and Rectal Surgeons

48

D uring the last few decades, the treatment of can-cer of the lower rectum has been characterized

by an increased use of sphincter-saving procedures[i.e., anterior resections (AR)]. It now is possible tomake a bowel anastomosis at literally any level in thepelvic region. These changes have been facilitatedprimarily by the introduction of stapling devices.

Furthermore, better understanding of the biology ofthe cancer has changed practice, e.g., the “5-cm rule”of the distal margin of resection has been generallyabandoned,1–3 and many now accept any distal mar-gin as long as the margin is tumor-free.4 Thus, thespecific indications for an abdominoperineal resec-tion (APR) have changed,5 and there has been a focuson sphincter-saving surgery5–10 and reconstructivemodalities that may improve functional outcome afterthis procedure.8,11

It has been argued that outcome (local recurrence(LR) and survival) is less favorable for tumors locatedin the lower rectum.12–14 Many theories have beenproposed to explain this phenomenon,12,15 and thesehave to some degree shaped treatment policies.

We still do not know whether it is the level of thetumor itself or other factors that lead to local failure.Surgeon-related factors are relevant, because there isa significant variability in outcome after rectal cancerresections.16–20 In addition, the technical refinementsexemplified by the introduction of mesorectal exci-sion have significantly improved the results after rec-tal cancer surgery.21 It is still not clear, however,whether the principle of mesorectal excision repre-sents an advantage for patients undergoing APR.15,22

This study was designed to evaluate the results oftreatment of cancer of the lower rectum and addressthe question of whether there are outcome differ-ences for those undergoing AR compared with thoseundergoing APR, using a large national cohort of pa-tients undergoing mesorectal excision.

PATIENTS AND METHODS

This study is part of the Norwegian Rectal CancerProject,23–25 whose objective is to improve rectal can-cer treatment at a national level. Major elements ofthis initiative, which started in 1993, included stan-dardization of surgery by educating surgeons in theprinciples of mesorectal excision, and standardizedhandling and reporting of the specimens according toQuirke’s principles,26 benchmarking the importanceof the circumferential resection margin (CRM).24 Dataon every patient with rectal cancer in Norway are

entered into the Norwegian Rectal Cancer Registry,23

and each hospital receives reports about their ownresults compared with the national average.

The present cohort consists of 2,136 patients withrectal cancer treated, with curative intent, by total me-sorectal excision between November 1993 and De-cember 1999. All patients had a tumor located be-tween 0 and 12 cm from the anal verge and wereundergoing AR or APR. Patients treated by Hart-mann’s procedure were not included, because the in-dications of this resection are based on clinical fea-tures different from the AR and APR groups(emergency surgery, older patients, comorbidity). Be-cause local recurrence and survival are main outcomemeasures, neither the R2 resections were included.

Clinical data were submitted on project-specificforms to the Rectal Cancer Registry located at the Can-cer Registry of Norway. Data on histopathology wereretrieved from the Registry’s compulsory reportingsystem, and tumors were classified according to theTNM classification system.27 Date of death was ex-tracted from the Norwegian Cause of Death Registry.

Follow-up data were collected by routine remind-ers. The follow-up regimen adhered to the principlesestablished by the Norwegian Gastrointestinal CancerGroup, which included clinical examination, proctos-copy, ultrasound of the liver, chest x-ray, and serumcarcinoembryonic antigen. Commonly, follow-upconsultations were undertaken every third month fortwo years, and thereafter every six months until fiveyears. Follow-up was completed for all patients, andthe median follow-up time was 44 (range, 22–97)months. Local recurrence rates are given as the sum ofisolated LR and LR with concomitant distant metasta-ses; survival rates denote overall (crude) survival.

Analyses and Statistical Methods

The patient, tumor, and treatment characteristicsare described using frequency tables according to tu-mor level and operative procedure (AR vs. APR) andwere analyzed using chi-squared statistics (Tables 1and 2). The rates of LR and overall survival were ana-lyzed by univariate statistical models (Kaplan-Meierand log-rank tests; Tables 3 and 4). Time to occur-rence of LR and death is given by stratified multivari-ate Cox regression analyses (Figs. 1–4). Because theobjective was to consider differences of long time sur-vival, the analyses do not include 60 (2.7 percent)patients who died within 30 days of the operation.Variations in the distribution of fragile patients (with

49CANCER OF THE LOWER RECTUMVol. 47, No. 1

cardiovascular disease or septic complications aftersurgery) might influence overall survival for thegroups being studied.

The impact of potential prognostic factors for LRand survival is analyzed by multivariate Cox propor-tional hazard regression models. The regressionswere performed backward with a cutoff P value of0.15, and the final results were confirmed by a for-ward procedure. The identification of independentpredictors was completed by univariate analyses.

Significant variables were included in the finalmodel (Table 5), in which the best prognostic groupfor each variable acts as reference, with a hazard ratio(HR) > 1 for those at more risk for LR or death. If onevariable was significant in either of the analyses of LR

or survival, it was incorporated into both models. Ra-diation was included, based on significant impact inthe univariate analysis, although not fulfilling statisti-cal significance (P = 0.08) in the final multivariatemodel. The analyses were performed using the statis-tical package for the social sciences program (SPSSInc., Chicago, IL).

RESULTS

In the 74-month inclusion period, 2,136 patients(1,243 (58 percent) males; median age, 69 (range, 18–94) years) were treated by a total mesorectal exci-sion23 for an adenocarcinoma located within 12 cm of

Table 1.Variables Related to Tumor Level

Tumor Level

Variable 0–5 cm 6–8 cm 9–12 cm P Value

Age (yr) 0.07<50 52 (7) 25 (4) 54 (7)50–59 113 (14) 91 (16) 119 (15)60–69 190 (24) 172 (31) 225 (29)70–79 307 (39) 196 (35) 276 (35)�80 129 (16) 74 (13) 113 (14)

Male/female ratio 432/359 (55/45) 333/225 (60/40) 478/309 (61/39) 0.034Type of resection <0.001

APR 673 (85) 119 (21) 29 (4)AR 118 (15) 439 (79) 758 (96)

Tumor status (T) <0.0011 84 (11) 57 (10) 78 (10)2 236 (30) 177 (32) 198 (25)3 369 (47) 289 (52) 458 (58)4 102 (13) 35 (6) 53 (7)

Node status (N) 0.9030 536 (68) 378 (68) 535 (68)1 182 (23) 125 (22) 174 (22)2 72 (9) 55 (10) 78 (10)

TNM stageI 268 (34) 203 (36) 231 (29) 0.032II 269 (34) 175 (31) 304 (39)III 254 (32) 180 (32) 252 (32)

Differentiation 0.001High 57 (7) 38 (7) 64 (8)Moderate 589 (74) 427 (76) 614 (78)Low 107 (14) 53 (10) 58 (7)Missing 38 (5) 40 (7) 51 (6)

Perforation <0.001Yes 101 (13) 42 (8) 41 (5)No 690 (87) 516 (92) 746 (95)

Involved CRM 0.001Yes 84 (11) 29 (5) 50 (6)No 707 (89) 529 (95) 737 (94)

Adjuvant radiotherapy <0.001Yes 115 (15) 48 (9) 51 (6)No 676 (85) 510 (91) 736 (94)

APR = abdominoperineal resection; AR = anterior resection; CRM = circumferential resection margin.Data are presented as numbers with percentages in parentheses unless otherwise specified.

50 WIBE ET AL Dis Colon Rectum, January 2004

the anal verge. The tumor was located 0 cm to 5 cmfrom the anal verge in 791 patients (37 percent), from6 cm to 8 cm in 558 patients (26 percent), and from 9cm to 12 cm in 787 patients (37 percent); 1,315 pa-tients (62 percent) were treated by AR and 821 (38percent) by APR.

Thirty-three percent (702 patients) were Stage I, 35percent (748 patients) Stage II, and 32 percent (686patients) Stage III. Consequently 67 percent had ahigh-risk tumor (Stages II and III); 190 patients (9percent) had a T4 tumor.

Intraoperative perforation of the bowel wall oc-curred in 184 resections (9 percent), and the CRM wasinvolved (CRM �1 mm) by tumor in 163 patients (8

percent). Radiotherapy was given to 214 patients (10percent): 124 patients (6 percent) preoperatively and90 patients (4 percent) postoperatively. Chemo-therapy was not an integral part of the Norwegiantreatment policy for rectal cancer during this period.23

Characteristics Related to Tumor LevelThe frequencies of patient and tumor characteris-

tics related to the tumor level are shown in Table 1.Age distribution was similar for all tumor levels. Theproportion of females with tumors in the lower level(45 percent) was higher compared with tumors in theintermediate (40 percent) and upper levels (39 per-cent; P = 0.034).

Table 2.Variables Related to Type of Resection

Type of Resection

Variable APR AR P Value

Age (yr) 0.001<50 50 (6) 81 (6)50–59 103 (13) 220 (17)60–69 203 (25) 384 (29)70–79 320 (39) 459 (35)�80 145 (18) 171 (13)

Male/female ratio 472/349 (57/43) 771/544 (59/41) 0.603Tumor level (cm)

0–5 673 (82) 118 (9) <0.0016–8 119 (14) 439 (33)9–12 29 (4) 758 (58)

Tumor status (T) <0.0011 91 (11) 128 (10)2 240 (29) 371 (28)3 374 (46) 742 (56)4 116 (14) 74 (6)

Node status (N)0 562 (69) 887 (68) 0.5991 181 (22) 300 (23)2 77 (9) 128 (10)

TNM stage 0.514I 282 (34) 420 (32)II 281 (34) 467 (36)III 258 (31) 428 (32)

Differentiation 0.002High 70 (9) 89 (7)Moderate 597 (73) 1,033 (79)Low 106 (13) 112 (9)Missing 48 (6) 81 (6)

Perforation <0.001Yes 131 (16) 53 (4)No 690 (84) 1,262 (96)

Involved CRMYes 95 (12) 68 (5) <0.001No 726 (88) 1,247 (95)

Adjuvant radiotherapy <0.001Yes 135 (16) 79 (6)No 686 (84) 1,236 (94)

APR = abdominoperineal resection; AR = anterior resection; CRM = circumferential resection margin.Data are presented as numbers with percentages in parentheses unless otherwise specified.

51CANCER OF THE LOWER RECTUMVol. 47, No. 1

T4 tumors were more frequent (13 percent) in thelower rectum than in the higher levels (6 and 7 per-cent; P < 0.001), although the tumor diameter wassimilar at all levels (data not given). The N status didnot differ according to tumor level, but at the highestlevel there were fewer Stage I and more Stage II tu-mors (P = 0.032) than in the lower and intermediatelevels. Of the tumors in the lower level, 14 percenthad low differentiation vs. 10 and 7 percent in theintermediate and upper levels, respectively (P =0.001). Bowel or tumor perforation during resectionoccurred in 5 percent of the resections of the tumorsat the highest level, 8 percent at the intermediatelevel, and 13 percent at the lower level (P < 0.001).

Tumor involvement of the CRM was identified in 6percent of cancers at the upper level, and in 5 and 11percent at the intermediate and lower levels, respec-tively (P = 0.001). Radiotherapy was used more oftenfor distal tumors, preoperatively and postoperatively;altogether, 15 percent of low-level tumors and 6 per-cent of high-level tumors were irradiated (P < 0.001).

Characteristics Related to Typeof Resection

Patient and treatment characteristics according totype of resection are described in Table 2. The age

distribution was significantly different in the AR groupcompared with the APR group. Younger patients (<70years) underwent AR more often, with older patientsbeing more likely to undergo APR (P = 0.001). Therewere 14 percent T4 tumors in the APR group vs 6percent in the AR group (P < 0.001). The distributionsof N status and TNM stages were similar for APR andAR. Of the tumors in the APR group, 13 percent hadlow differentiation compared with 9 percent in the ARgroup (P = 0.002).

Intraoperative perforation of the tumor or bowelwall occurred in 16 percent of the APRs and 4 percentof the ARs (P < 0.001), and frequency of tumor in-volvement of the CRM was 12 percent after APR vs. 5percent after AR (P < 0.001). Radiotherapy was usedmore often in the APR group compared with the ARgroup; 135 patients (16 percent) who underwent APRand 79 patients (6 percent) who underwent AR (P <0.001) were given preoperative or postoperative ra-diotherapy.

Local Recurrence and Survival

The five-year overall LR rate was 12 percent (95percent confidence interval (CI), 10–13). The localrecurrence rate was 15 percent (95 percent CI, 12–18)in the lower level, 13 percent (95 percent CI, 9–16) in

Table 3.Five-Year Local Recurrence and Overall Survival According to Tumor Level

Local Recurrence (P = 0.014a) Survival (P < 0.001a)

Tumor Level No. of Patients n (%) 95% CIb % 95% CIb

0–5 cm 791 95 (15) 12–18 59 55–636–8 cm 558 59 (13) 9–16 62 57–669–12 cm 787 62 (9) 7–11 69 65–73Total 2,136 216 (12) 10–13 63 61–66

CI = confidence interval.aLog-rank test.bKaplan-Meier test.

Table 4.Five-Year Local Recurrence and Overall Survival According to Type of Resection

Local Recurrence (P = 0.008a) Survival (P < 0.001a)

Resection No. of Patients n (%) 95% CIb % 95% CIb

AR 1,315 117 (10) 8–12 68 66–71APR 821 99 (15) 12–18 55 52–59Total 2,136 216 (12) 10–13 63 61–66

APR = abdominoperineal resection; AR = anterior resection; CI = confidence interval.aLog-rank test.bKaplan-Meier test.

52 WIBE ET AL Dis Colon Rectum, January 2004

the intermediate level, and 9 percent (95 percent CI,7–11) in the upper level (P = 0.014; Table 3). The LRrate after AR and APR was 10 percent (95 percent CI,8–12) and 15 percent (95 percent CI, 12–18), respec-tively (P = 0.008; Table 4).

The cumulative LR rate with time was similar in thelower and intermediate levels, but significantly less inthe upper level (Fig. 1). There was, however, no dif-ference in LR rate according to resection type afteradjusting for prognostic factors (Fig. 2; Table 5). Fiftypercent of the recurrences occurred within 19 monthsand 90 percent within 40 months.

The five-year overall survival rate for the entire pa-tient population was 63 percent (95 percent CI, 61–66): 69 percent (95 percent CI, 65–73) at the highestlevel, 62 percent (95 percent CI, 57–66) at the inter-

mediate level, and 59 percent (95 percent CI, 55–63)at the lowest level (P < 0.001; Table 3). The multivari-ate analyses, which adjusted for all significant vari-ables, showed that the level of the tumor was close tobe identified as an independent predictor of overallsurvival (P = 0.072; Table 5; Fig. 3). After AR and APR,the five-year survival rate was 68 percent (95 percentCI, 66–71) and 55 percent (95 percent CI, 52–59), re-spectively (P < 0.001; Table 4; Fig. 4).

Prognostic Factors

The multivariate analyses (Table 5) demonstratedthat T and N status, tumor level, intraoperative perfo-

Figure 1. Local recurrence rates according to tumor level(multivariate Cox regression analysis).

Figure 2. Local recurrence rates according to type of re-section (AR vs. APR) (multivariate Cox regression analy-sis). APR = abdominoperineal resection; AR = anteriorresection.

Figure 3. Crude survival according to tumor level (multi-variate Cox regression analysis).

Figure 4. Crude survival according to type of resection(AR vs. APR) (multivariate Cox regression analysis). APR= abdominoperineal resection; AR = anterior resection.

53CANCER OF THE LOWER RECTUMVol. 47, No. 1

ration, and involved CRM influenced LR rates,whereas resection type did not. Thus, for patients un-dergoing AR or APR, given an identical T and N status,tumor level, and frequency of perforation and margininvolvement, the LR rates were not significantly dif-ferent (Fig. 2).

T4 tumors increased the LR risk by a factor (HR) of4.7 (95 percent CI, 1.9–11.7), and intraoperative per-foration increased LR with an HR of 2.9 (95 percent CI,2.0–4.2). The observed LR rate (44 months medianfollow-up) was 23 percent after perforation and 9 per-cent in the group who had no perforation.

Overall survival declined with increasing age; themortality risk for those older than 79 years was in-

creased (HR, 6.1; 95 percent CI, 3.8–9.9) comparedwith those younger than 50 years (Table 5). Femalessurvived better than males (HR, 1.4; 95 percent CI,1.2–1.6). Tumor characteristics, such as T and N statusand tumor differentiation, also influenced survival,and the HR for T4 tumors, compared with T1 tumors,was 3.6 (95 percent CI, 2.3–5.7).

The multivariate analysis revealed reduced survivalat the intermediate level compared with the high level(HR, 1.3; 95 percent CI, 1–1.6) but no difference be-tween the high and the low tumor level (HR, 1.1; 95percent CI, 0.9–1.5; Table 5). Thus, the univariateanalysis of survival (Table 3) showing better survivalfor tumors in the high level group than for those at the

Table 5.Factors Influencing Local Recurrence and Survival in 2,136 Patients With Rectal Cancera

Local Recurrence Survival

Variable Hazard Ratio 95% CI P Value Hazard Ratiob 95% CI P Value

Age (yr)<50 1 0.338 1 <0.00150–59 1.2 0.6–2.3 1.2 0.7–2.160–69 1.5 0.8–2.9 1.9 1.2–3.170–79 1.1 0.6–2.1 3.1 1.9–5�80 1.3 0.7–2.7 6.1 3.8–9.9

Male/female ratio 1.1/1 0.9–1.5 0.37 1.4/1 1.2–1.6 <0.001Tumor level (cm)

9–12 1 0.027 1 0.0726–8 1.6 1.1–2.9 1.3 1–1.60–5 1.8 1.1–2.3 1.1 0.9–1.5

Tumor status (T)1 1 <0.001 1 <0.0012 1.4 0.6–3.4 1.2 0.8–1.93 2.8 1.2–6.6 2.4 1.6–3.64 4.7 1.9–11.7 3.6 2.3–5.7

Node status (N)0 1 <0.001 1 <0.0011 1.9 1.4–2.7 1.8 1.5–2.12 2.4 1.6–3.6 2.8 2.2–3.5

DifferentiationHigh 1 0.876 1 0.001Medium 1 0.5–1.7 0.9 0.7–1.3Low 1.1 0.6–2.1 1.5 1–2.1

Resection typeAR 1 0.504 1 0.039APR 1.2 0.7–1.8 1.3 1–1.6

PerforationNo 1 <0.001 1 0.017Yes 2.9 2–4.2 1.3 1.1–1.7

Involved CRMNo 1 0.043 1 0.003Yes 1.6 1–2.4 1.4 1.1–1.8

RadiationYes 1 0.176 1 0.082No 1.4 0.9–2.2 1.3 1–1.6

CI = confidence interval; APR = abdominoperineal resection; AR = anterior resection; CRM = circumferential resectionmargin.

an = 178 with missing values excluded.bHazard ratio increased by reduced survival.

54 WIBE ET AL Dis Colon Rectum, January 2004

low level could be explained by less favorable pa-tient, tumor, and treatment-related factors (i.e., intra-operative perforation and margin involvement) in thelower regions of the rectum, particularly in the grouptreated with APR (Tables 1 and 2).

Although the type of resection did not influence theLR risk, there was a significantly better survival in theAR group. The risk of dying was increased by 30 per-cent (HR, 1.3; 95 percent CI, 1–1.6) among those whounderwent APR compared with those having an AR.Intraoperative perforation of the bowel wall increasedthe mortality risk by 30 percent (HR, 1.3; 95 percentCI, 1.1–1.7), and tumor involvement of the CRM in-creased mortality with 40 percent (HR, 1.4; 95 percentCI, 1.1–1.8).

The five-year survival rate was 31 percent (95 per-cent CI, 24–40) in the group with an involved CRM,and 66 percent (95 percent CI, 64–69) in the groupwith a noninvolved margin. Radiotherapy was notidentified as an outcome predictor in the multivariateanalysis of local recurrence (HR, 1.4; 95 percent CI,0.9–2.2) or of survival (HR, 1.3; 95 percent CI, 1–1.6;P = 0.082).

DISCUSSION

It is a commonly held opinion—based on previousobservational studies12–14—that cancers of the lowerrectum have a less favorable oncologic outcome com-pared with those at higher levels. A critical review ofthe literature did not reveal any explicit cause for apossible inherent poor prognosis for low-level tu-mors.

Miles, who introduced APR in 1906, based his workon the notion that the spread of tumors of the lowerrectum occurred toward the lymph nodes outside thelevator ani muscles. APR was thought to deal with thisproblem. Later studies have not upheld Miles’ con-cept.15,22

A common problem in some studies that addressthis question is the lack of multivariate analyses thatinclude main predictors to avoid confounding, espe-cially the prognostic impact of intraoperative perfora-tion and the involvement of the CRM.12,13,15,22 Fur-thermore, the focus of the studies has not beenexclusively related to data that could elucidate thepotential effect of tumor level, e.g., APR has beenclaimed to be oncologically inferior to AR.15 It wasassumed that APR increased the risk of implantationof shed tumor cells, leading to more local recurrencesthan an AR. In our opinion, these arguments were not

based on solid data; the above-mentioned study wastoo small and firm conclusions cannot be drawn. Incontrast, a much larger study, the Stockholm Rectal Can-cer Study28 (n = 1,292), could not identify any differ-ence in LR rates after AR and APR (24 and 28 percent,respectively), in nonradiated patients, although me-sorectal excision was not performed in this series.

In addition, there also is a suspicion that many pub-lished studies are potentially biased (selection bias),because they present data from single centers withunclear referral practices. The present study, which isbased on a national cohort of patients treated in manyhospitals over a contemporaneous period of time,gives a representative view of a population with rectalcancer and of treatment practice in routine care.

A significant characteristic of some seminal rectalcancer studies is the substantial variation in LR ratesbetween hospitals and surgeons16–20; we know thatsurgical competence and skill determine out-come.19,29 Such data may support the assumption thatthe main problem with cancers in the lowest regionmay be related to technical proficiency. Therefore, itcould be presumed that routine use of radiotherapyfor cancers of the lower rectum is a substitute forinferior surgical performance.

The data presented in this article support this view,because all patients received a standardized resection(mesorectal excision) and, in contrast to earlier re-ports,12–14 the present study can identify no majordifference (range, 6 percent) in LR rates related totumor level. Similarly, there was no difference in LRrates between AR and APR for comparable patientand tumor characteristics (Fig. 2). However, the sur-vival rate was better for high-level tumors than it wasfor low-level tumors (Table 3), without tumor levelbeing identified as a true predictor of survival (Table5). This could be explained by less favorable patient,tumor, and treatment factors in the lower regions ofthe rectum (Table 1). This is illustrated by the fact thatthere were more T4 tumors in the lower levels of therectum (13 vs. 6 and 7 percent in the two higher lev-els; Table 1), and thus, more T4 tumors in the APRthan the AR group (14 vs. 6 percent; Table 2). Tumorswith low differentiation also were more common atthe low level compared with tumors of the high level(14 vs. 7 percent).

Radiotherapy was given to 214 patients (10 per-cent), most often as preoperative treatment of T4 tu-mors or postoperatively after intraoperative perfora-tion of the bowel wall or tumor involvement of theCRM. Thus, radiotherapy was used more frequently

55CANCER OF THE LOWER RECTUMVol. 47, No. 1

for cancers of the lower rectum treated by APR(Tables 1 and 2), although in the present study radio-therapy had no independent prognostic impact onlocal recurrence.

Treatment-related factors also differed among tu-mor levels. Intraoperative perforation of the tumor orbowel wall was more common for tumors in thelower rectum being treated by an APR. We know thatperforation of the bowel wall is a major cause of localrecurrence30; this was verified by the multivariate re-gression analysis presented in Table 5, confirming thesignificance of the difference in LR rate between thegroup with and without perforation (23 vs. 9 percent,respectively). The present data also showed that thelower the tumor the more often the CRM was involvedby the tumor (Table 1). An involved CRM is followedby a significantly increased rate of LR and reducedsurvival24 (Table 5). In this study, the five-year sur-vival was 66 percent in the group with uninvolvedCRM compared with 31 percent in the group withinvolved CRM.

Thus, this study provides evidence that there areseveral independent factors with influence on out-come according to the level of the tumor. Frequencytables and univariate statistics describe the results atdifferent levels, but they do not explain the cause ofthese differences. The present results demonstrate theimportance of addition of multivariate statisticalanalyses to avoid confounding31–33 the search of in-dependent outcome predictors that can guide treat-ment strategies.

CONCLUSIONS

The characteristics of the tumor, bowel perforation,and involvement of the CRM are independent factorsthat significantly influence the outcome of cancer ofthe lower rectum. With regard to the LR rate, the levelof the tumor is not a strong predictor, because thisrate increases by only 6 percent from the highest tothe lowest level. Furthermore, the type of resectiondoes not influence the risk of LR.

Because all the patient and tumor characteristics arefixed at the moment of diagnosis, including the levelof the tumor, only the treatment-related factors can beinfluenced by the surgeon. The main message of thecurrent data is, therefore, that intraoperative perfora-tion and/or involved margin should be avoided whileoperating on cancers of the lower rectum. If surgery isoptimized, preventing intraoperative perforation andinvolvement of the CRM, the prognosis for cancers of

the lower rectum seems not to be inherently differentfrom that for tumors at higher levels. In that case, thelevel of the tumor or the type of resection will not beindicators for selecting patients for radiotherapy.

ACKNOWLEDGMENTS

The authors thank all the Norwegian surgeons and47 hospitals who have contributed diligently and en-thusiastically to the cancer surgery and reported theirdata over the years. We also thank the pathologistswho examined the specimens.

APPENDIX 1.

Steering Group

The Norwegian Gastrointestinal Cancer Group

Chairman

Olav Dahl, Department of Oncology, HaukelandHospital, Bergen.

Project Group Members

Tormod Bjerkeset, Innherred Hospital; ErikCarlsen, Ullevaal Hospital (chairman); Olav Dahl,Haukeland Hospital; Tor J. Eide, National Hospital;Trond Ellingsen, Harstad Hospital; Tore Gauperaa,Aust-Agder Central Hospital; Tom Gerner, OpplandCentral Hospital Lillehammer; Øyvind Irtun, TromsøUniversity Hospital; Hartwig Kørner, Rogaland Cen-tral Hospital; Frøydis Langmark, Cancer Registry ofNorway; Helge E. Myrvold, St. Olavs Hospital; JarleNorstein, Cancer Registry of Norway; Arne Skarstein,Haukeland Hospital; Johan N. Wiig, Norwegian Ra-dium Hospital.

Participating Hospitals and Surgeons

Aker Hospital (Arild Nesbakken, M.D.), AkershusCentral Hospital (Arne E. Færden, M.D.), Aust-AgderCentral Hospital (Tore Gauperaa, M.D.), BuskerudCentral Hospital (Ulf Jacobsen, M.D.), Bærum Hospi-tal (Rocio Rosales, M.D.), Diakonhjemmet Hospital(Jan H. Solhaug, M.D.), Diakonissehjemmets Hospital(Trond Haugstvedt, M.D.), Hedmark Central Hospital,Elverum (Øyvind Graadal, M.D.), Hedmark CentralHospital, Hamar (Øyvind Graadal, M.D.), HammerfestHospital (Svein Hammelbo, M.D.), Harstad Hospital

56 WIBE ET AL Dis Colon Rectum, January 2004

(Trond Ellingsen, M.D.), Haugesund Hospital (KnutSvendby, M.D.), Haukeland Hospital (Arne Skarstein,M.D.), Innherred Hospital (Tormod Bjerkeset, M.D.),Kirkenes Hospital (Lennart Wählby, M.D.), Kongs-vinger Hospital (Mikael Bech, M.D.), KristiansundHospital (Håkan Steen, M.D.), Larvik Hospital (OddRuistuen, M.D.), Lærdal Hospital (Fritjof Lund-Larsen,M.D.), Molde Hospital (Arve Sæbø, M.D.), Moss Hos-pital (Torgeir Løvig, M.D.), Møre og Romsdal CentralHospital (Sverrir Olafsson, M.D.), Namdal Hospital(Hallvard Græsli, M.D.), Nordland Central Hospital(Hans Wasmuth, M.D.), Oppland Central HospitalGjøvik (Olav Høstmælingen, M.D.), Oppland CentralHospital, Lillehammer (Bjørn H. Nilsen, M.D.), OrkdalSanitetsforenings Hospital (Bjørn G. Hansen, M.D.),Rana Hospital (Ranveig K. Aspevik, M.D.), The Nor-wegian Radium Hospital (Johan N. Wiig, M.D.), TheNational Hospital (Øystein Mathisen, M.D.), RingerikeHospital (John Colin Poole, M.D.), Rjukan Hospital(Kjetil Unneberg, M.D.), Rogaland Central Hospital(Hartwig Kørner, M.D.), Sogn og Fjordane CentralHospital (Nils Sletteskog, M.D.), Stensby Hospital (Jo-han Lykke, M.D.), Stord Hospital (Olav Stray, M.D.),Stokmarknes Hospital (Rune Svensen, M.D.),Telemark Central Hospital (John Bjørn Nilsen, M.D.),Tromsø University Hospital (Øyvind Irtun, M.D.), St.Olavs Hospital (Helge E. Myrvold, M.D.), UllevaalUniversity Hospital (Erik Carlsen, M.D.), Vefsn Hos-pital (Øistein Ylvisaker, M.D.), Vest-Agder CentralHospital (Leif Ø. Heen, M.D.), Vestfold Central Hos-pital (Geir Haarberg, M.D.), Volda Hospital (YngveNordervald, M.D.), Voss Hospital (Hans JørgenNielsen, M.D.), Østfold Central Hospital (Thorleif E.Wilhelmsen, M.D.).

REFERENCES

1. Nivatvongs S. Management of adenocarcinoma of thelow rectum—introduction. World J Surg 1992;16:428–9.

2. Williams NS, Dixon MF, Johnston D. Reappraisal of the5 centimetre rule of distal excision for carcinoma of therectum: a study of distal intramural spread and of pa-tients’ survival. Br J Surg 1983;70:150–4.

3. Karanjia ND, Schache DJ, North WR, Heald RJ. “Closeshave” in anterior resection. Br J Surg 1990;77:510–2.

4. Phillips RK. Adequate distal margin of resection for ad-enocarcinoma of the rectum. World J Surg 1992;16:463–6.

5. Lavery IC, Lopez-Kostner F, Fazio VW, Fernandez-Martin M, Milsom JW, Church JM. Chances of cure arenot compromised with sphincter-saving procedures forcancer of the lower third of the rectum. Surgery 1997;122:779–85.

6. Köhler A, Athanasiadis S, Ommer A, Psarakis E. Long-term results of low anterior resection with intersphinc-teric anastomosis in carcinoma of the lower one-third ofthe rectum: analysis of 31 patients. Dis Colon Rectum2000;43:843–50.

7. Andreola S, Leo E, Belli F, et al. Distal intramural spreadin adenocarcinoma of the lower third of the rectumtreated with total rectal resection and coloanal anasto-mosis. Dis Colon Rectum 1997;40:25–9.

8. Berger A, Tiret E, Parc R, et al. Excision of the rectumwith colonic J pouch-anal anastomosis for adenocarci-noma of the low and mid rectum. World J Surg 1992;16:470–7.

9. Leo E, Belli F, Andreola S, et al. Total rectal resectionand complete mesorectum excision followed by co-loanal anastomosis as the optimal treatment for lowrectal cancer: the experience of the National CancerInstitute of Milan. Ann Surg Oncol 2000;7:125–32.

10. Rullier E, Goffre B, Bonnel C, Zerbib F, Caudry M, SaricJ. Preoperative radiochemotherapy and sphincter-saving resection for T3 carcinomas of the lower third ofthe rectum. Ann Surg 2001;234:633–40.

11. Guillem JG. Ultra-low anterior resection and coloanalpouch reconstruction for carcinoma of the distal rec-tum. World J Surg 1997;21:721–7.

12. Enker WE, Havenga K, Polyak T, Thaler H, Cranor M.Abdominoperineal resection via total mesorectal exci-sion and autonomic nerve preservation for low rectalcancer. World J Surg 1997;21:715–20.

13. Jatzko GR, Jagoditsch M, Lisborg PH, Denk H, Klimpfin-ger M, Stettner HM. Long-term results of radical surgeryfor rectal cancer: multivariate analysis of prognostic fac-tors influencing survival and local recurrence. Eur J SurgOncol 1999;25:284–91.

14. Lopez-Kostner F, Lavery IC, Hool GR, Rybicki LA, FazioVW. Total mesorectal excision is not necessary for can-cers of the upper rectum. Surgery 1998;124:612–8.

15. Heald RJ, Smedh RK, Kald A, Sexton R, Moran BJ. Ab-dominal excision of the rectum—an endangered opera-tion. Dis Colon Rectum 1997;40:747–51.

16. Holm T, Johansson H, Cedermark B, Ekelund G,Rutqvist L-E. Influence of hospital- and surgeon-relatedfactors on outcome after treatment of rectal cancer withor without preoperative radiotherapy. Br J Surg 1997;84:657–63.

17. McArdle C. ABC of colorectal cancer. Primary treat-ment—does the surgeon matter? BMJ 2000;321:1121–3.

18. Porter GA, Soskolne CL, Yakimets WW, Newman SC.Surgeon-related factors and outcome in rectal cancer.Ann Surg 1998;227:157–67.

19. Smedh K, Olsson L, Johansson H, Åberg C, AnderssonM. Reduction of postoperative morbidity and mortalityin patients with rectal cancer following the introductionof a colorectal unit. Br J Surg 2001;88:273–7.

20. Killingback M, Barron P, Dent OF. Local recurrence af-

57CANCER OF THE LOWER RECTUMVol. 47, No. 1

ter curative resection of cancer of the rectum withouttotal mesorectal excision. Dis Colon Rectum 2001;44:473–83.

21. Heald RJ, Ryall RD. Recurrence and survival after totalmesorectal excision for rectal cancer. Lancet 1986;II:1479–82.

22. Law WL, Chu KW. Impact of total mesorectal excisionon the results of surgery of distal rectal cancer. Br J Surg2001;88:1607–12.

23. Wibe A, Møller B, Norstein J, et al. A national strategicchange in treatment policy for rectal cancer—implementation of total mesorectal excision as routinetreatment in Norway. A national audit. Dis Colon Rec-tum 2002;45:857–66.

24. Wibe A, Rendedal PR, Svensson E, et al. Prognosticsignificance of the circumferential resection margin fol-lowing total mesorectal excision for rectal cancer. Br JSurg 2002;89:327–34.

25. Søreide O, Norstein J. Local recurrence after operativetreatment of rectal carcinoma: a strategy for change. JAm Coll Surg 1997;184:84–92.

26. Quirke P, Durdey P, Dixon MF, Williams NS. Local re-currence of rectal adenocarcinoma due to inadequatesurgical resection. Histopathological study of lateral tu-mour spread and surgical excision. Lancet 1986;2:996–9.

27. UICC. TNM classification of malignant tumours. 5th ed.New York: Wiley-Liss, Inc. 1997.

28. Holm T, Rutqvist L-E, Johansson H, Cedermark B. Ab-dominoperineal resection and anterior resection in thetreatment of rectal cancer: results in relation to adjuvantpreoperative radiotherapy. Br J Surg 1995;82:1213–6.

29. Martling L, Holm T, Rutqvist L-E, Moran BJ, Heald RJ,Cedermark B. Effect of a surgical training programmeon outcome of rectal cancer in the County of Stock-holm. Lancet 2000;356:93–6.

30. Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 forcolon and rectal cancer surgery. J Natl Cancer Instit2001;93:583–96.

31. Bokey EL, Öjerskog B, Chapuis PH, Dent OF, NewlandRC, Sinclair G. Local recurrence after curative excisionof the rectum for cancer without adjuvant therapy: roleof total anatomical dissection. Br J Surg 1999;86:1164–70.

32. Bokey EL, Chapuis PH, Dent OF, et al. Factors affectingsurvival after excision of the rectum for cancer: a mul-tivariate analysis. Dis Colon Rectum 1997;40:3–10.

33. Dent OF, Chapuis PH, Bokey EL, Newland RC. Meth-odology and reporting in studies of local recurrenceafter curative excision of the rectum for cancer. Br JSurg 2001;88:1476–80.

58 WIBE ET AL Dis Colon Rectum, January 2004