Recurrence and Survival after SurgicalManagement of Rectal Cancer

Alison Ross, MD, Conrad Rusnak, MD, Brian Weinerman, MD, Peter Kuechler, MD, Allan Hayashi, MD,Gordon MacLachlan, MD, Ewan Frew, MD, William Dunlop, MD, Victoria, British Columbia

BACKGROUND: Reported local recurrence rates forrectal cancer are significantly reduced using acombination of superior surgical technique, inthe form of total mesorectal excision, and rou-tine radiotherapy. In an attempt to determine theeffectiveness of current local management strate-gies, a review of Vancouver Island Cancer Centrepatients with rectal cancer was performed and theoverall local recurrence rate was identified.

METHODS: We retrospectively reviewed the chartsof 272 rectal cancer patients from 1988 to 1998.Two hundred and twenty-nine patients met inclu-sion criteria. Analysis of patient factors includedage, gender, type of surgery, and adjuvant ther-apy. Tumors were assessed for level, stage, andgrade. Local recurrence and distant metastaseswere also documented. Variables influencing lo-cal recurrence in this group were identified anddisease-free and actuarial survival determined.

RESULTS: Of 229 patients analyzed, 12.7% (29)had local recurrences. Variables influencing localrecurrence were number of positive lymphnodes, vascular invasion, and neural invasion.There was no significant difference in local re-currence between patients having anterior resec-tion and those having abdominoperineal resec-tion. None of the patients who receivedpreoperative radiotherapy had a local recur-rence. Actuarial disease-free survival was 87% at5 years.

CONCLUSIONS: Limiting local recurrence is one ofthe most important goals in the treatment of rec-tal cancer. It is essential to identify those pa-tients with “high risk” tumors as identified byendorectal ultrasound or pathologic features.These patients comprise the group most likely tobenefit from a routine mesorectal excision com-bined with adjuvant radiotherapy. Am J Surg.1999;177:392–395. © 1999 by Excerpta Medica,Inc.

Local recurrence following treatment for rectal canceris a major cause of morbidity and mortality. Cure isseldom a possibility once a recurrence is present, and

palliation is often difficult and unsuccessful. The reportedrange of local recurrence rates following surgical treatmentfor rectal cancer has varied from 4% to 50%.1 Local recur-rence rates of 4% have been reported by Heald and Ryall2

and MacFarlane et al.3 who employ the technique of totalmesorectal excision. Limiting local recurrence is onlyslightly less important than cure. With the knowledge ofthese results, a proposal was made to analyze the localrecurrence rate in our region to determine if implementingthe total mesorectal excision technique was a worthwhileendeavor in an attempt to limit local recurrence.

MATERIAL AND METHODSA retrospective review of 272 patients diagnosed with

rectal cancer, who were referred to the Vancouver IslandCancer Centre from January 1988 to June 1998, was per-formed. All patients who underwent primary treatmentelsewhere (20), who did not undergo surgical therapy (17),or who underwent defunctioning colostomy only (6) wereexcluded from the analysis. The remaining 229 patients,who were treated by one of 34 surgeons in seven centres onVancouver Island, comprised the patient population ana-lyzed in this review. All data were collected by one indi-vidual (ACR).

Curative resection was defined as negative margins patho-logically and absence of residual metastatic disease. Localrecurrence was defined as the presence of tumor in thepelvis, perineum or at the anastomosis, as diagnosed byhistologic, radiologic, or clinical examination. Disease-freesurvival was defined as the time from the primary treatmentto the time recurrence was detected.

The modified Astler-Coller classification was used forstaging the tumors initially. However, TNM staging wasadded for universality. Histologic grading of the tumors waslimited to definition of well, moderate, or poor differenti-ation, and presence of neural, lymphatic, or vascular inva-sion. Tumor level was identified by the assessment ofoperative reports, pathology reports, and endoscopic exam-inations. Tumors were arbitrarily defined as being lowerrectum (0 to 5 cm), middle rectum (6 to 10 cm), upperrectum (11 to 15 cm), or NOS (not otherwise specified).

Analysis of patient factors included age, gender, type ofsurgery, and adjuvant therapy. Tumor factors analyzed in-cluded tumor level, histology, invasion, and stage. Localrecurrence and distant metastases were also documentedalong with calculation of actuarial survival.

Statistical analysis was performed using SPSS for Win-dows Overview. Using Pearson’s test, variables correlatingwith local recurrence were identified. Univariate and mul-

From the Department of Surgical Services, Capital Health Re-gion, and the Vancouver Island Cancer Centre, Victoria, BritishColumbia, Canada.

Requests for reprints should be addressed to Conrad Rusnak,MD, 302-2020 Richmond Avenue, Victoria, BC, Canada V8R 6R5.

Presented at the 85th Annual Meeting of the North PacificSurgical Association, Tacoma Washington, November 13–14,1998.

392 © 1999 by Excerpta Medica, Inc. 0002-9610/99/$–see front matterAll rights reserved. PII S0002-9610(99)00080-X

tivariate analyses determined independent variables influ-encing local recurrence and distant metastases. Disease-free survival and overall survival were determined usingactuarial life table analysis.

RESULTSPatient Factors

Of 229 patients, 90 (39.3%) were female and 139(60.7%) were male. The median age of patients at the timeof diagnosis was 65.5 years. One hundred and twentypatients (52.4%) underwent anterior resection, 99 (43.2%)had abdominoperineal resections, and 10 (4.4%) had localexcision only. Eleven (4.8%) underwent preoperative ra-diotherapy. Eighty-nine patients (38.9%) had postopera-tive chemotherapy and radiotherapy, 22 (9.6%) had post-operative radiotherapy alone, 14 (6.1%) had postoperativechemotherapy alone, and 93 (40.6%) received no adjuvanttherapy.

Tumor FactorsTumor level was high rectum in 61 patients (26.6%),

middle rectum in 84 patients (36.7%), lower rectum in 78patients (34.1%), and not otherwise specified in 6 patients(2.6%). Surgical procedures performed according to tumorlevel are shown in Figure 1. Forty-five patients (19.7%)had well-differentiated tumors, 163 (71.1%) had moder-ately well differentiated tumors, 18 (7.9%) had poorlydifferentiated tumors, and in 3 patients (1.3%) the tumorgrade was unavailable. Modified Astler-Coller staging de-fined that 11 patients (4.8%) had stage A disease, 33(14.4%) had stage B1 disease, 68 (29.7%) had stage B2disease, 15 (6.6%) had stage C1 disease, 80 (34.9%) hadstage C2 disease, 5 (2.2%) had stage C3 disease, and 17(7.4%) had stage D disease. Comparable modified Astler-Coller and TNM staging is shown in Table I.

RecurrencesOverall there were 29 (12.7%) patients who had a local

recurrence. Actuarial disease-free survival was 87% at 5years. Demographics of patients with local recurrence areshown in Table II. Of these, 3 were stage B1, 13 were B2,1 was C1, 8 were C2, 1 was C3, and 3 were stage D at thetime of diagnosis. Local recurrence occurred in 15 patientswho underwent anterior resection and in 14 patients whohad abdominoperineal resections. No patients with local

recurrence had preoperative radiotherapy. Four underwentpostoperative radiotherapy alone, 1 had postoperative che-motherapy alone, 5 had combined postoperative chemora-diotherapy, and 19 had no adjuvant therapy.

Exclusion of patients with metastatic disease (17) andpositive margins (7) yielded a local recurrence rate of11.2%. The mean time to detection of local recurrence was16.3 months. Overall, 26 patients (11.8%) were diagnosedwith metastatic disease after their initial surgical interven-tion.

AnalysisThe results of linear regression analysis are shown in

Table III. There was significant correlation between localrecurrence and number of positive lymph nodes (P 50.001), presence of vascular invasion (P ,0.001), and

Figure 1. Type of surgery relative to tumor level.

TABLE IModified Astler-Coller Stages and Corresponding TNM

Stages

Number ofPatients MAC TNM

11 A T1N0M033 B1 T2N0M068 B2 T3N0M00 B3 T4N0M03 C1 T1N1M0

12 C1 T2N1M00 C1 T2N2M0

61 C2 T3N1M019 C2 T3N2M05 C3 T4N1M00 C3 T4N2M0

17 D TanyNanyM1

TABLE IIDemographics of Patients with Local Recurrence

CharacteristicNumber of

Patients

GenderMale 19Female 10

SurgeryAnterior resection 15Abdominoperineal resection 14

Time to local recurrence16.3 months (range 3–45)

Stage of diseaseA 0B1 3B2 13C1 1C2 8C3 1D 3

Adjuvant therapyPreoperative radiotherapy 0Postoperative radiotherapy 4Postoperative chemotherapy 1Postoperative chemo/radiotherapy 5No adjuvant therapy 19

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THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999 393

presence of neural invasion (P ,0.001). According to lifetable analysis, 87% of patients were free of local recurrenceat 5 years (Figure 2). Using the same analysis, the freedomfrom disease for distant metastasis at 5 years was 83%. Theproportion of patients free from local recurrence or meta-static disease was 73%. Overall survival at 50 months was67%.

COMMENTSLocal recurrence following surgical treatment for rectal

cancer is a major cause of morbidity and mortality. Five-year survival in patients with local recurrence is less than5% with a median survival of only 7 months.4 There is asevere negative impact on the quality of life of patientswho suffer local recurrence because successful palliation isdifficult to achieve.5 Consequently, although survival is themost important goal in the treatment of rectal cancer,limiting local recurrence is only marginally less so.

Reported local recurrence rates vary considerably withrates from 4% to 50% (median 18.3%) being reported.1

This translates into significant morbidity and mortality.Consequently, attempts were made to limit local recur-rence with the use of adjuvant therapy. With the additionof adjuvant radiotherapy, surgical outcomes were oftensalvaged with a significant reduction in local recurrencerates.6,7,11,12 Pelvic recurrences following surgical inter-vention are reported to be decreased by 33% to 50% withthe addition of radiotherapy.6–8

However, the benefits of adjuvant radiotherapy in reduc-ing local recurrence seem to be dependent on a high localrecurrence rate following surgical intervention. With localrecurrence rates of less than 10%, there are no data dem-onstrating a beneficial effect with the addition of radio-

therapy.9 In other words, further attempts to reduce localrecurrence rates with aggressive radiotherapy in patientswhose local recurrence rates are less than 10% may trans-late into treatment of an inordinate number of patients toachieve a significant reduction.10 Thus, if local recurrencerates following surgical therapy alone can be reduced to lessthan 10%, then perhaps routine use of preoperative radio-therapy may become necessary only in those patients iden-tified as having high-risk tumors as determined by endo-rectal ultrasound. Furthermore, in patients identified ashaving high-risk tumors, as determined by pathologic anal-ysis, postoperative adjuvant radiotherapy will be beneficialas well.

In this series, none of the 11 patients who receivedpreoperative radiotherapy had a local recurrence. Con-versely, 29 of 218 patients who did not have preoperativeradiotherapy had local recurrences. This result, althoughachieving a P value of only 0.1, may be of considerableclinical significance. It is difficult to draw conclusions froma series with such small numbers; however, a trend towardimproved results with patients receiving preoperative ra-diotherapy is evident. Randomized controlled trials arecurrently in progress to delineate those patients who wouldbenefit most from adjuvant radiotherapy.

In an attempt to limit local recurrence in patients withrectal cancer, Heald et al2,3 have proposed the technique oftotal mesorectal excision. This technique involves “com-plete resection of the enveloping mesorectal tissues in acovering of thin but recognizable fascia.”3 This is achievedusing sharp dissection under direct vision throughout thecase. With this technique, local recurrence rates of 4%have been reported.2,3 The mesorectum appears to be ofgreat importance in the local spread of rectal cancer.

In our series, the overall actuarial local recurrence ratewas 13%. Applying exclusion criteria, the local recurrencerate in patients without metastatic disease at the time ofsurgery was 12.3%. Patients with stage B and C disease hada local recurrence rate of 12.9%. This result is not limitedto those patients who underwent surgical treatment alone.

To further delineate, patients with stage B disease ac-counted for 16 of the 29 local recurrences. Of these, 3 wereB1 and 13 were B2. Adjuvant therapy was used in 25% ofthese patients. Patients with B1 tumors received no adju-vant therapy. Of those with B2 tumors, 9 received noadjuvant therapy, 2 received postoperative radiotherapy,and 2 received combination postoperative chemoradio-therapy. In this group of patients, total mesorectal excisionmay have resulted in a marked decrease in the local recur-rence rate. With these patients excluded, local recurrencerates approach 5%, which is comparable with those ofother centers performing total mesorectal excision. It re-mains difficult to extrapolate these conclusions and applythem to patients with stage C disease. However, Heald andMacFarlane’s work has consistently shown remarkably lowrates of local recurrence in this subset of patients.

In this series, it appears that the subgroup of patients mostlikely to benefit from routine total mesorectal excision arethose with stage B1 and B2 disease (16 of 101). It is alsoclinically apparent, although not statistically significant,that preoperative radiotherapy plays an important role inthe overall management of rectal cancer patients.

TABLE IIIVariables Assessed in Determining Factors Influencing

Local Recurrence

Variable P Value

Stage 0.222Lymphatic invasion 0.321Vascular invasion ,0.001Neural invasion ,0.001Positive margins 0.483Tumor spillage 0.703Number of positive nodes 0.001

Figure 2. Time to local recurrence.

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394 THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 MAY 1999

CONCLUSIONThe most important goal in the treatment of rectal can-

cer, next to cure, is to limit the rate of local recurrence.Local recurrence rates of 4% have been reported in theliterature with the use of total mesorectal excision alone.In an effort to improve the rate of local recurrence of rectalcancer on Vancouver Island, we performed a retrospectivechart review and subsequently have identified a subset ofpatient who would benefit from standard total mesorectalexcision. In addition, those patients deemed to have high-risk tumors would benefit from adjuvant radiotherapy. Assuch, this technique should become part of the armamen-tarium of the general surgeon in the treatment of rectalcancer. This will be accomplished through a continuingmedical education program.

REFERENCES1. McCall JL, Cox MR, Wattchow DA. Analysis of local recur-rence rates after surgery alone for rectal cancer. Int J Colorectal Dis.1995;10:126–132.2. Heald RJ, Ryall RDH. Recurrence and survival after total me-sorectal excision for rectal cancer. Lancet. 1986:1479–1482.3. MacFarlane JK, Ryall RDH, Heald RJ. Mesorectal excision forrectal cancer. Lancet. 1993:457–460.4. Gunderson LL, Sosin H. Areas of failure found at reoperation

(second look or symptomatic look) following curative surgery foradenocarcinoma of the rectum. Clinicopathologic correlation andimplications for adjuvant therapy. Cancer. 1974;34:1278–1292.5. McLeod RS. Symposium on rectal cancer: 2. Local recurrenceafter surgery for rectal cancer. Can J Surg. 1997;40:353–357.6. Dahl O, Horn A, Halvorsen JF, et al. Low dose preoperativeradiation postpones recurrences in operable rectal cancer. Results ofa randomized multicenter trial in western Norway. Cancer. 1990;66:2286–2294.7. Preoperative short-term radiation therapy in operable rectalcarcinoma. A prospective randomized trial. Stockholm Rectal Can-cer Study Group. Cancer. 1990;66:49–55.8. Tveit KM, Guldvog I, Hagen S, et al. Randomized controlledtrial of postoperative radiotherapy and short term time-scheduled5-fluorouracil against surgery alone in the treatment of Dukes B andC rectal cancer. Br J Surg. 1997;84:1130–1135.9. Arbman G, Nilsson E, Hallbook O, Sjodahl R. Local recurrencefollowing total mesorectal excision for rectal cancer. Br J Surg.1996;83:375–379.10. Zaheer S, Pemberton JH, Farouk R, et al. Surgical treatment ofadenocarcinoma of the rectum. Ann Surg. 1998;227:800–811.11. McKinnon JG. Symposium on rectal cancer: 1. A summary.Can J Surg. 1997;40:352.12. Cummings BJ. Symposium on rectal cancer: 3. The case foradjuvant radiotherapy for rectal cancer. Can J Surg. 1997;40:358–362.

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