quality of life after potentially curative treatment for locally advanced rectal cancer

Quality of Life after Potentially Curative Treatmentfor Locally Advanced Rectal Cancer

Gabriella Palmer, MD,1,2 Anna Martling, MD, PhD,1 Pernilla Lagergren, RN, PhD,1

Bjorn Cedermark, MD, PhD,1 and Torbjorn Holm, MD, PhD1

1Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden2Section of Coloproctology, Department of Surgery, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden

Background: Patients with locally advanced rectal cancer have a poor prognosis and theearly and late postoperative morbidity is high. The aim of this study was to assess health-related quality of life (HRQL) in patients treated with extensive surgical resections for locallyadvanced rectal cancer and to compare the results with those in patients treated for primarilyresectable rectal cancer.Methods: Between 1991 and 2003, 142 patients with locally advanced rectal cancer had an

extensive resection at the Karolinska Hospital in Stockholm, Sweden. A HRQL assessmentwith the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30and QLQ-CR38 questionnaires was performed in patients alive and disease free in 2005. Theresults were compared with an age- and sex-matched reference group of patients with pri-marily resectable rectal cancer having had total mesorectal excision alone.Results: The study group of 43 patients (81% of eligible) scored clinically and statistically

signicantly lower in global quality of life, role function, physical function, social function,and body image and reported a higher degree of pain and fatigue compared with the referencegroup of 80 patients. In the study group, men scored lower than women in global quality oflife, role functioning and social functioning and reported more problems with fatigue.Conclusion: Several aspects of HRQL are impaired in disease-free patients treated for lo-

cally advanced rectal cancer. This knowledge may be useful in the preoperative counsellingand postoperative support of these patients.

In 1015% of patients with rectal cancer thetumour is locally advanced; i.e., the cancer infiltratesan adjacent organ or structure. With modern mag-netic resonance imaging (MRI) techniques, the localtumour growth can be carefully mapped preopera-tively and the surgical procedure may be planned indetail. In addition, preoperative radiochemotherapymay downsize and downstage the tumour, which mayfacilitate a complete local tumour clearance.

Improved surgical techniques, with extended totalmesorectal excision (TME) and en bloc resections ofinvolved organs, have augmented the rate of poten-tially curative resections (R0) for primary advancedtumours. Several studies have shown up to a 60% R0resection rate after extensive procedures, leading toimproved outcomes.14

In patients with locally recurrent rectal cancer,the prognosis has traditionally been poor, but inthe last decade the survival after neoadjuvantradiochemotherapy and extensive surgery has im-proved also in these patients.510 With R0 resec-tions, 5-year survival rates of 3460% have beenreported.2,11

Published online August 21, 2008.Address correspondence and reprint requests to: Gabriella Pal-

mer, MD; E-mail: [email protected]

Published by Springer Science+Business Media, LLC 2008 The Society ofSurgical Oncology, Inc.

Annals of Surgical Oncology 15(11):31093117

DOI: 10.1245/s10434-008-0112-y

3109

Preoperative radiochemotherapy and advancedsurgical procedures may result in high rates of post-operative complications and long-term morbiditywith urinary problems, altered defecation, pain, fa-tigue and sexual problems.1214 In addition, manypatients may have one or two stomas.Thus, even if the patient is cured of cancer, the

health-related quality of life (HRQL) may be dra-matically altered after the treatment. Assessment ofHRQL during and after treatment has been estab-lished as an important outcome measure in cancerpatients. The HRQL concept has several dierentdenitions, but today there is a relative consensusregarding HRQL as a subjective and multidimen-sional phenomenon, including a number of life as-pects inuencing individual well-being. Severalstudies have examined the change of HRQL overtime in rectal cancer patients, often with a baselinescore preoperatively or before radiochemother-apy,1517 while other studies have compared HRQLwith population references.18 Furthermore, recentstudies have shown HRQL scores to be of prognosticsignicance for survival and surgical complications inpatients with colorectal cancer.16,19,20 However thereis a lack of studies of long-term HRQL in patientswho have undergone extensive surgery for advancedrectal cancer.The aim of the study was therefore to assess long-

term HRQL in disease-free patients after extensivesurgical resections for locally advanced rectal cancerand to compare HRQL between these patients andpatients with primarily resectable rectal cancer, wherea TME resection alone had been performed. Inaddition, the study patients were compared with thegeneral population in Sweden regarding HRQL.

METHODS

The Stockholm Colorectal Cancer Study Groupwas set up in 1980 with the aim to improve outcomesin colorectal cancer. Treatment guidelines and pro-tocols have been established and since 1995 all pa-tients with colorectal cancer in the Stockholm regionhave been prospectively registered at the RegionalOncologic Centre (ROC) with detailed informationon treatment and outcome.In 1991, a multimodality treatment protocol aim-

ing to standardise preoperative evaluation andtreatment in patients with rectal cancer, includinglocally advanced and recurrent rectal cancer, wasestablished at Karolinska University Hospital. Clin-ical data on patients included in this program have

been prospectively and compared with the register atthe ROC in Stockholm.2123 Between 1991 and 2003,142 patients with locally advanced primary or locallyrecurrent rectal cancer, including four patients withadvanced sigmoid cancer inltrating a pelvic organ,underwent extensive surgery. The study includespatients with both primary advanced and locallyrecurrent tumours, as they are treated similarlywith preoperative radiochemotherapy and extensivesurgery.All patients alive and known to be disease-free in

March 2005 were contacted by mail and asked tocomplete quality-of-life questionnaires. Patients notresponding received a reminding phone call from acontact nurse.Patients with primarily operable rectal cancer from

nine dierent hospitals in the Stockholm region,resected with TME surgery alone, were selected fromthe ROC register as a reference group and individu-ally matched 2:1 according to age, gender and timeafter surgery. Clinical data on the reference groupwere retrieved from the ROC cancer register.All patients responding to the rst questionnaires

and still alive 1.5 years later were contacted to com-plete the questionnaires a second time, and 34patients responded to this second follow-up.In 2000, Michelson et al.24 established normative

HRQL data from the Swedish population aged1879 years and reported chronic health problemsbased on the EORTC QLQ-C30 questionnaire (seedetailed information below) with respect to age,gender and sociodemographic characteristics. Acomparison was made between the study group andthe aforementioned background population. Since noreference scores exist for people aged over 79 years inthe background population, patients older than79 years in the study group were excluded in thiscomparison.

Health-Related Quality-of-Life Instrument

HRQL was evaluated with the disease-specicquestionnaire EORTC QLQ-C30 version 3.0,25 ageneral core cancer-specic instrument, and thecolorectal module QLQ-CR38,26 both developed bythe European Organisation for Research and Treat-ment of Cancer (EORTC). These instruments havebeen previously validated and are used specically incancer-related measures of HRQL. The EORTCQLQ-C30 comprises a global quality-of-life scale, vefunctional scales (physical, role, cognitive, emotionaland social), three symptom scales (fatigue, pain andnausea/vomiting), and six single items evaluating

G. PALMER ET AL.3110

Ann. Surg. Oncol. Vol. 15, No. 11, 2008

different aspects of HRQL (dyspnoea, insomnia,appetite loss, constipation, diarrhoea and nancialdifculties). The QLQ-CR38 module was developedto assess symptoms specic to colorectal cancer andcontains four functional scales (body image, sexualfunctioning, sexual enjoyment and future perspective)and eight items and symptom scales (micturitionproblems, chemotherapy side effects, gastrointestinaltract symptoms, male sexual problems, female sexualproblems, defecation problems, stoma-related prob-lems and weight loss). Each item has four responsealternatives, not at all, a little, quite a bit, andvery much, except for the global health and qual-ity-of-life scale which has seven alternatives fromvery poor to excellent. Missing data were han-dled according to the EORTC Scoring Manual.27 Allquestionnaire responses were linearly transformed toa 0100 scale. A high score in the global quality-of-life scale and the function scales represents a higherlevel of quality of life and function, respectively,while a high score for symptom scales/items repre-sents a higher degree of symptoms or dysfunction.

Ethical Consent

This study was approved by the regional ethicalcommittee in Stockholm. Informed consent was ob-tained from the patients prior to inclusion in thestudy.

Statistical Analyses

Mean HRQL scores with 95% condence intervalswere calculated for the follow-up measure. Based onprevious research,28,29 a difference in mean scores ofat least 10 units and nonoverlapping 95% condenceintervals between groups was considered to be ofclinical relevance. The parametric independent-by-group t-test was used to test if dierences in meanscores between the total study group and the totalreference group were of statistical signicance at the5% level (P< 0.05). The data were also analysedusing the nonparametric Wilcoxon rank-sum test.Since the results were similar, only the results fromthe parametric analyses are reported.Based on comparisons with the Swedish back-

ground population, dierences in expected meanscores (population based) and observed mean scoresfrom the study group were tested for signicanceusing a single-sample t-test.All analyses were preformed using the statistical

software package Statistica.

RESULTS

During the study period between 1991 and 2003,142 patients with locally advanced primary or locallyrecurrent rectal cancer were included in the studycohort. In March 2005, 53 (37%) alive and disease-free patients were asked to complete HRQL ques-tionnaires. The response rate was 89% (47/53). Twopatients were deceased, two had severe dementia/alcohol abuse, one had moved abroad and one wastoo ill and old to respond. Of the 47 responders, 4were found to have recurrent cancer and weretherefore excluded from further analysis.To obtain a reference group of 86 patients (2:1

matched), 112 patients with primarily operable rectalcancer resected with TME surgery alone were asked toll in questionnaires. Twenty- six did not respond. Ofthe remaining 86 patients, 6 reported disseminateddisease and were therefore excluded. Thus, 43 patientswere included in the study group and 80 patients wereincluded in the reference group.Clinical characteristics of the study group and the

reference group are shown in Table 1. The medianfollow-up time between surgery and patient assess-ment of HRQL varied between 9 and 149 months inthe study group and between 7 and 151 months in thereference group. In 26 patients, surgery was per-formed due to locally advanced primary rectal cancerand in 4 because of locally advanced sigmoid cancer.The remaining 13 patients were operated on for lo-cally recurrent disease. In the reference group allpatients had primary resectable rectal canceraccording to the ROC registry. All but four patientswith locally advanced rectal cancer had receivedpreoperative radiotherapy or radiochemotherapy.The reasons for not receiving neoadjuvant treatmentwere advanced age or symptomatic cardiovasculardisease. Surgery was performed with intraoperativeradiation (IORT) in 13 patients. IORT was given atthe discretion of the operating surgeon if uncertaintyprevailed regarding the radically of the resection. Inthe reference group, 76% (61/80) of the patients re-ceived preoperative radiotherapy. En bloc resectionsof one or multiple other organs were performed in 35patients; including gynaecological organs (11), blad-der (11), ureter (4), seminal vesicle (8), prostate orpart of prostate (8), small bowel (9), part of sacrum(9) and part of the pelvic sidewall (9). The remainingeight patients had an extended TME, a resectionextending outside the mesorectal fascia with removalof adjacent tissue, for example autonomic nerves orpresacral fat. A permanent stoma was constructed in86% (37/43) of the patients. Nine patients had a

QOL IN LOCALLY ADVANCED RECTAL CANCER 3111


urinary stoma by an ileal conduit and two patientswere reconstructed with an orthotopic bladder.In the reference group 75% (60/80) had a low

anterior resection; two with a remaining temporarydiverting ileostomy. Twenty had a stoma after anabdominoperineal resection (APR) or Hartmannsprocedure.All patients in the study group were preoperatively

staged by MRI or computed tomography (CT) scanas having T4 tumours. Postoperative histopathologyshowed T3 or T4 tumours in the majority, but sevenhad T0T2 tumour, probably due to downstagingafter radiochemotherapy. In the reference group,86% (69/80) of the patients had T2 or T3 tumours.The T stage of a local recurrence was recorded asunknown if the recurrence was in the pelvis butoutside the rectum.

General Health-Related Quality of Life

Comparisons in EORTC QLQ-C30 between thestudy group and the reference group are shown inTable 2. Mean scores of role functioning and socialfunctioning showed a clinically relevant difference and

a statistically signicant difference (P< 0.05) with ahigher level of function in the reference group. Also,global quality of life and physical functioning werefound to be statistically signicantly better in the ref-erence group. The symptom score for fatigue and painwas clinically signicantly higher in the study groupand fatigue was found to be statistically signicant.The worse response alternatives, quite a bit andvery much, for pain were reported in 33% of thepatients in the study group. In evaluating fatigue, 45%of the patients scored quite a bit or very much.Thirty-four patients in the study group who were

alive at 1.5 years after their rst assessment of HRQLwere asked to respond to a second assessment usingthe same questionnaires. No clinically or statisticallysignicant dierences were found in the mean scoresbetween the rst and second assessments (data notshown).When dierences in relation to gender were ana-

lysed in the study group, men reported clinicallysignicantly worse problems in global quality of life,role functioning and social functioning, and sueredmore from fatigue compared with women. Socialfunctioning also diered statistically signicantly. No

TABLE 1. Clinical characteristics in patients treated with extended surgery for locally advanced rectal cancer (study group) andin patients after total mesorectal excision (reference group)

Study group (n = 43) Reference group (n = 80)

Sex female/male (%) 21/22 (49/51) 41/39 (51/49)Median age at surgery (range) 66 (2888) 65 (3589)Median follow-up after surgery in months (range) 30 (9149) 32 (7151)Mean follow-up after surgery in months 43 45Type of tumourPrimary rectal cancer 26 80Primary sigmoid cancer 4Local recurrence 13Preoperative treatmentShort course RT 25 Gy 7 61Long course RT 50 Gy 18Previous RT/chemotherapy 5 0Combination 9 1None 4 18ProcedureLAR 7 60APR 18 13Hartmanns procedure 6 7Pelvic excenteration 11 0Explorative laparotomy 1 0

Excision of other organs 35 0Stoma (%) 37 (86) 22 (28)Tumour stageT0 5 0T1 1 6T2 1 29T3 25 40T4 8 3Unknown 3 2

RT, radiotherapy; GY, Gray; LAR, low anterior resection; APR, abdominoperineal resection.



gender dierences were seen in the reference group.The single-item scores of dyspnoea, insomnia, andnancial diculties showed no clinically or statisti-cally signicant dierences in mean score betweensthe groups and are therefore not reported in the table.

Colorectal-Specic Symptoms

Comparisons between the study group and thereference group regarding the colorectal-specic

symptoms (EORTC QLQ-CR38) are presented inTable 3. With the exception of body image and def-ecation problems, no clinically or statistically signif-icant differences were seen between the groups. Nogender differences were seen regarding the colorectal-specic symptoms.The questions concerning sexuality (sexual func-

tioning, sexual enjoyment, and male and female sex-uality) had a low response frequency and were notfurther analysed. The symptoms of chemotherapy

TABLE 2. EORTC QLQ-C30 in patients after extended surgery for advanced rectal cancer (study group) compared withpatients after total mesorectal excision (reference group) presented as mean scores with 95% condence intervals (CI)

Study group Reference group

P valuea

Mean score (95% CI) Mean score (95% CI)

Female Male Total Female Male Totaln = 21 n = 22 n = 43 n = 41 n = 39 n = 80

Overallb

Global health status 64 (5375) 55 (4367) 60 (5268) 70 (6378) 68 (5976) 69 (6374) 0.05Functionsb

Physical 74 (6266) 71 (6082) 72 (6480) 82 (7588) 81 (7388) 81 (7686) 0.04Role 66 (5082) 56 (3973) 61 (4972) 82 (7489) 74 (6384) 78 (7284) 0.00Emotional 80 (7288) 77 (65-88) 79 (7285) 81 (74-87) 80 (7388) 81 (7685) 0.64Cognitive 86 (7795) 75 (6685) 80 (7487) 84 (7791) 85 (7991) 85 (8085) 0.30Social 73 (6285) 54 (4068) 63 (5473) 81 (7290) 77 (6887) 79 (7385) 0.01Symptomsc

Fatigue 29 (1840) 41 (2954) 35 (2744) 23 (1631) 26 (1834) 25 (1930) 0.03Nausea and vomiting 6 (-113) 10 (120) 8 (314) 4 (07) 5 (09) 4 (17) 0.16Pain 25 (1337) 28 (1442) 27 (1736) 17 (1024) 19 (1127) 18 (1323) 0.09Appetite loss 7 (-115) 18 (432) 13 (421) 8 (313) 7 (113) 8 (311) 0.21Constipation 3 (-18) 11 (120) 7 (213) 12 (420) 18 (728) 15 (921) 0.11Diarrhea 32 (1350) 29 (1542) 30 (1941) 28 (1739) 21 (1330) 25 (1832) 0.40

a Independent t-test was used to calculate the statistical signicance at the 5% level between the total mean in the study group and referencegroup.

b Score range from 0 to 100; a high score represents a better level of quality of life and function.c Score range from 0 to 100; a high score represents more severe symptoms.

TABLE 3. EORTC QLQ-CR38 in patients after extended surgery for advanced rectal cancer (study group) compared withpatients after total mesorectal excision (reference group) presented as mean scores with 95% condence intervals (CI)

Study group Reference group

P valuea

Mean score (95%CI) Mean score (95% CI)

Female Male Total Female Male Totaln = 21 n = 22 n = 43 n = 41 n = 39 n = 80

Functionb

Body image 58 (4473) 51 (3766) 55 (4564) 76 (6785) 82 (7490) 79 (7385) 0.00Future perspective 62 (4677) 65 (4981) 64 (5374) 63 (5373) 69 (6178) 66 (6073) 0.66Symptomsc

Micturition problems 29 (1642) 30 (2040) 29 (2137) 28 (2234) 28 (2334) 28 (2432) 0.75Gastrointestinal 16 (1122) 17 (1024) 17 (1221) 22 (1727) 17 (1322) 20 (1221) 0.26Defecation problem 13 (-2348) 16 (-233) 14 (325) 25 (2031) 30 (2336) 27 (2331) 0.06Stoma-related problems 34 (2246) 37 (2648) 36 (2843) 47 (1084) 23 (1136) 30 (1843) 0.43Weight loss 11 (-123) 8 (015) 9 (216) 14 (720) 10 (317) 12 (717) 0.50

a Independent t-test was used to calculate the statistical signicance at the 5% level between the total mean in the study group and referencegroup.

b Score range from 0 to 100; a high score represents a better level of quality of life and function.c Score range from 0 to 100; a high score represents more severe symptoms.



side eects showed no clinically or statisticallysignicant dierences in mean score between thegroups and are not reported in the table.

Health-Related Quality of Life in Relationto the Swedish Background Population

Comparisons between the study patient group andthe age-matched Swedish background population arepresented in Table 4. The study group reportedclinically and statistically signicantly worse scores inglobal quality of life and physical, role and socialfunctioning. Moreover, the study group had higherdegree of fatigue and diarrhoea compared with meanscores from the Swedish background population.

DISCUSSION

Patients who received preoperative radiochemo-therapy and extensive surgery for locally advancedrectal cancer score their HRQL slightly worse thanpatients treated for primarily resectable rectal cancer.Global quality of life, physical functioning, rolefunctioning, social functioning and body image wereimpaired, and the symptoms of fatigue, pain anddefecation problems were more pronounced in thestudy group. Also, women scored better than men inall functions, including body image, and reportedfewer problems with symptoms. This is inconsistent

with population-based studies where women gener-ally score worse than men, especially in older agegroups.24,30

The merits of this study are the prospectively col-lected data, the high response rate and the use ofvalidated and reliable questionnaires. The prospec-tively collected data in combination with the highresponse rate reduces the risk of selection bias and theuse of validated, multidimensional questionnairesacts against information bias. However, there are alsosome limitations: disparities between the study groupand the reference group, the variable follow-up time,the small sample size and the hospital-based selectionof patients. The dierences in age and sex distributionbetween the study group and the reference groupwere due to the exclusion of six reference patientswho reported disseminated disease when lling intheir questionnaires. The follow-up time was slightlylonger in the reference group because of diculties innding matched pairs in the Stockholm region thatmet all three matching criteria. As this study includespatients operated on between 1991 and 2002, thefollow-up time varied signicantly. The shortest fol-low-up time in the study group was 9 months, whichwas chosen in order to avoid the immediate postop-erative period. It has been reported that up to 60% ofpatients have short-term postoperative complicationsafter extensive pelvic surgery,8,11,31 and almost half ofall cancer patients experience depression during therst year of follow-up.32 A more stable physical andpsychological condition is usually present afterapproximately 1 year in disease-free patients.15,16 Thesmall number of patients in the study group reducesthe power of the study and implies a risk for error bychance. However, despite the small sample size, theclinically relevant differences in scores betweengroups seem to have power enough to demonstratestatistical signicance. The hospital-based design mayincrease the risk of selection bias, while the high re-sponse rate should reduce such error. Obtaining alarge study population of disease-free patients treatedfor locally advanced rectal cancer from a single centreis difcult since the overall survival is rather low witha curative resection rate of about 5060%.The patients in the study group scored lower than

the patients in the reference group in almost allfunctions, including global quality of life, but thedierences were relatively small. The observed dete-rioration in HRQL after potentially curative surgeryin patients with locally advanced rectal cancer is inaccordance with clinical experience. However, in thelong-term perspective, these patients adapt quite wellto daily life. This experience was reported by Guren

TABLE 4. Difference in expected (population based) andobserved scores (study group) for EORTC QLQ-C30 in 33patients treated for advanced rectal cancer aged 3079 years

Observedscores

Expectedscores

Obs.-exp.Difference P valuea

Overallb

Global quality of life 57.3 68.8 -11.5 0.004Functionsb

Physical 72.7 85.7 -12.9 0.007Role 57.8 84.9 -27.1 0.000Emotional 78.7 83.3 -4.6 0.179Cognitive 81.2 87.4 -6.2 0.108Social 59.4 90.0 -30.6 0.000Symptomsc

Fatigue 35.9 21.4 14.5 0.004Pain 28.3 20.9 7.4 0.173Appetite loss 10.1 3.9 6.2 0.128Constipation 7.1 6.0 1.1 0.737Diarrhea 34.4 4.9 29.5 0.000

a Differences in observed and expected means computed bysingle-sample t-test.

b Score range from 0 to 100; a high score represents a better levelof quality of life and function.

c Score range from 0 to 100; a high score represents more severesymptoms.



et al. who studied HRQL in patients with advancedrectal cancer having a urinary diversion.33 The psy-chosocial aspects after pelvic exenteration have alsobeen reviewed by Turns,32 showing a response shiftand improved HRQL as these patients adapt to theirsituation during long-term follow-up.The impaired body image found in the study group

may reect the high frequency of diverting stomas.Also, role and physical function may be aected if thepatient has an anxiety for stoma-related problems indaily life activities. Studies comparing HRQL afterAPR and anterior resection (AR) have found worsebody image scores in APR patients.34 AlthoughGruman et al.35 reported a better general HRQLafter APR than after AR, body image score waslowered after both APR and AR. No apparent dif-ferences in HRQL related to colostomy were found ina recent Cochrane review of HRQL after rectal can-cer surgery.36 However, all studies concerning HRQLin colorectal cancer patients are quite small and therole of a stoma in relation to body image remainsunclear.The symptoms of fatigue and pain were increased

in patients with locally advanced cancer. In a previ-ous study of the same cohort of patients, 30% of thepatients had persistent pain, requiring analgesics, as along-term complication and a few had had sacralinsuciency fractures after radiation.11

The questions on sexuality in QLQ-CR38 weredicult to handle correctly due to frequently missingresponses, especially from females. Questions onsexuality may be irrelevant and embarrassing formany in an elderly population. Also, the construct ofthe questionnaire was dicult to understand. SinceApril 2007 a new version of the colorectal moduleQLQ-CR29 has been developed, in which the ques-tions concerning sexuality and incontinence havebeen revised.37

The long-term HRQL in patients treated for rectalcancer will be inuenced not only by the surgicaltrauma and possible postoperative complications, butalso by functional problems such as impaired bowelfunction, including incontinence and urinary prob-lems which may be caused by preoperative radio-therapy.13,14 However, symptoms may diminish withtime, and patients may adapt to a lower state offunction. If anxiety for relapse fades, social andemotional functioning will continue to improve. Afew studies have followed patients over time. Engelet al.34 followed curatively resected rectal cancerpatients for 4 years and reported a signicant overallimprovement over time, except for cognitive func-tioning and dyspnoea. In a study of patients with

locally advanced rectal cancer, Allal et al.15 assessedHRQL preoperatively and 1 year postoperatively andfound that all patients improved in global quality oflife and emotional function, but a signicantimprovement of gastrointestinal problems was re-ported only in patients with a stoma.In the present study, no signicant dierence over

time was present when patients reassessed theirHRQL 1.5 years after the rst follow-up assessment,which is probably explained by the wide variation infollow-up time from surgery to the rst follow-upassessment. If a patient has been disease-free forseveral years, the HRQL is not likely to have changeddramatically 18 months later.Women in the study group scored higher (i.e. bet-

ter) than men regarding functions and lower (i.e.worse) regarding symptoms, a nding which wasunexpected. This gender dierence was not seen inthe reference group; and in population-based studieson HRQL, women generally score worse than men,especially in higher age groups.24,30 The gender dif-ference in the study group is difcult to explain, butmay to some extent be due to the higher rate of pelvicexenteration in men, resulting in two stomas andimpotency.Most of the HRQL mean scores for function and

symptoms were both clinically and statistically sig-nicantly worse when the study group HRQL scoreswere compared with the HRQL scores in the Swedishbackground population.24 Although patients withrecurrent disease in both the study group and thereference group were excluded in this study, manypatients still live with the anxiety of cancer recurrenceand many have remaining physical symptoms due tocomplications after treatment. Camilleri-Brennanet al.38 compared HRQL in patients with recurrentrectal cancer and a group of patients with curativelyresected rectal cancer and found that the recurrencehad a profound effect on HRQL, affecting almost alldimensions. In this study, there was no differencebetween patients with recurrent rectal cancer andprimary advanced cancer (data not shown).It is obvious that patients who have had a poten-

tially life-threatening cancer and may have remainingdiscomfort after treatment cannot be expected toscore similarly in HRQL to the general population.HRQL is also strongly related to age. In Michelsonsstudy on HRQL in a random sample of the popula-tion in Sweden, the 7079 years age group scoredworse than the 6069 years age group for all func-tions except emotional function.24 In the currentstudy, 25% of the patients in the study group wereaged 80 years or more. Although the reference group



was age matched to the study group, it may be thatolder patients have more difculty improving theirHRQL after extensive procedures than after TMEalone.In conclusion, many aspects of HRQL are

impaired in disease-free patients treated for locallyadvanced rectal cancer, compared with patientstreated with TME alone for primarily resectablerectal cancer and compared with a Swedish back-ground population. Knowledge on posttreatmentHRQL in this patient group seems valuable to be ableto counsel the patient preoperatively and to giveadequate support after surgery.

ACKNOWLEDGEMENTS

Financial support was provided through the re-gional agreement on medical training and clinicalresearch (ALF) between the Stockholm county andthe Karolinska Institute. The study was also sup-ported by the Swedish Cancer Society, the CancerSociety in Stockholm and the Bengt Ihre Founda-tion. Toom Singnomklao at the Oncology Centre inStockholm has performed excellently in collectingand validating patient data. Madeleine Ahlberg hasprovided valuable help with collecting the question-naires.

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Quality of Life after Potentially Curative Treatment for Locally Advanced Rectal CancerAbstractMethodsHealth-Related Quality-of-Life InstrumentEthical ConsentStatistical AnalysesResultsGeneral Health-Related Quality of LifeTab1Colorectal-Specific SymptomsTab2Tab3Health-Related Quality of Life in Relation to the Swedish Background PopulationDiscussionTab4AcknowledgementsReferencesCR1CR2CR3CR4CR5CR6CR7CR8CR9CR10CR11CR12CR13CR14CR15CR16CR17CR18CR19CR20CR21CR22CR23CR24CR25CR26CR27CR28CR29CR30CR31CR32CR33CR34CR35CR36CR37CR38

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quality of life after potentially curative treatment for locally advanced rectal cancer

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