- Email: [email protected]
The impact of recurrent rectal cancer on quality of life
EJSO 2001; 27: 349–353 doi:10.1053/ejso.2001.1115, available online at http://www.idealibrary.com on
The impact of recurrent rectal cancer on quality of life J. Camilleri-Brennan and R. J. C. Steele University Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, Scotland
Aims: To determine, in patients operated upon for rectal cancer, the impact that tumour recurrence has on quality of life. Methods: Twenty-five patients, who had curative surgery for rectal cancer from 1992 to 1997, and who subsequently developed tumour recurrence, participated. Each patient was individually matched with two patients who also had rectal cancer surgery during the same period of time but were considered to be free of cancer. The patients were matched for age, gender, type of operation and socioeconomic status. They answered the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and CR38 quality of life questionnaires, as well as the SF36 II questionnaire, at least 1 year after surgery. Results: Patients with recurrent rectal cancer had significantly lower quality of life scores than cured patients in most dimensions, as measured by the three questionnaires. A significant difference was also seen in the global quality of life score on the QLQ-C30 (median scores 50 vs 75, z=4.015, P=0.0001). Conclusion: Recurrence of rectal cancer has a profound effect on quality of life, affecting most measurable dimensions. Treatment of recurrent cancer should not only be directed at the physical aspect of the disease, but also at its psychological and social aspects. 2001 Harcourt Publishers Ltd Key words: quality of life; rectal cancer; recurrent cancer; surgery.
INTRODUCTION Recurrence of rectal cancer after potentially curative surgery is a major problem. Tumour recurrence may be local, that is within the pelvis, or distant, commonly in the liver. The incidence of tumour recurrence varies from centre to centre. This is particularly true of local recurrence which has been reported to be as low as 2.6%1 and as high as 31.8%.2 Most of the tumours recur within the first 2 years post-operatively. Recurrent rectal cancer carries a high morbidity and a poor prognosis,3 and it is likely that the presence of recurrent rectal cancer leads to a poor quality of life. A study on patients with recurrent breast cancer showed that the quality of life of these patients was poor,4 but no formal quality of life studies have been carried out in patients with recurrent rectal cancer. It is not known which quality of life dimensions are affected, and to what extent the patients’ quality of life is impaired. The aim of this study was to measure the impact of
Correspondence to: Mr John Camilleri-Brennan FRCS, University Department of Surgery and Molecular Oncology, Level 6, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland. Tel: +44 (0)1382 660111; Fax: +44 (0)1382 641795; E-mail: [email protected] 0748–7983/01/040349+05 $35.00/0
recurrent tumour on patients’ quality of life using wellvalidated and reliable quality of life questionnaires. A comparison was made between patients with tumour recurrence and a matched group of patients with no evidence of recurrent local or metastatic rectal cancer who had been operated upon within the same time period.
PATIENTS AND METHODS Hospital records were used to identify patients who had primary curative surgery for rectal cancer from 1992 to 1997 at four hospitals in Scotland (Raigmore Hospital, Inverness; Ninewells Hospital, Dundee; Perth Royal Infirmary, Perth; Stracathro Infirmary, Brechin) and who were subsequently diagnosed with tumour recurrence after surgery. Local tumour recurrence was diagnosed radiologically and, in patients who had an anterior resection, using endoscopy and histological examination of biopsies. Distant tumour recurrence was diagnosed by rising carcinoembryonic antigen (CEA) and the presence of metastases on liver ultrasound and/or CT scan. Thirty patients who were alive with recurrent rectal cancer were identified and invited to participate in the study. Twenty-five of these patients agreed to participate. 2001 Harcourt Publishers Ltd
350
J. CAMILLERI-BRENNAN AND R. J. C. STEELE
Table 1 Demographic and clinical characteristics of participants Patients with tumour recurrence
Matched patients without tumour recurrence
25 64 (49–80) 16 9 5 16 4 14 11 6 (5–15) 24 (12–59)
50 67 (45–84) 32 18 11 33 6 28 22 7 (3–15) 22 (11–72)
Number Age∗ (years) Male Female Depcat 1 and 2 Depcat 3, 4 and 5 Depcat 6 and 7 APER Anterior resection Level of anastomosis† (cm) Months post-operatively‡
Abbreviations: Depcat, Deprivation Category; APER, abdominoperineal resection. ∗ Age expressed as median and range. † Level of anastomosis was measured in patients who had an anterior resection; values are expressed as median and range. ‡ Months post-operatively expressed as median and range.
Eleven had a local recurrence, 12 had distant metastases and two had both local and distant recurrence. Each patient with tumour recurrence was individually matched with two tumour-free patients for age (within 4 years of each other), gender, type of operation (abdominoperineal resection or anterior resection), and socioeconomic status (Table 1). Age, gender and socioeconomic status have been shown to have a significant effect on quality of life.5 Socioeconomic status (Deprivation Category) was determined using the Carstairs Index, an index of deprivation based on the postcode.6 The median time since surgery was similar in both groups. All patients were given the following quality of life questionnaires: the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and the Medical Outcomes Study ShortForm 36 version 2 (SF36 II). The patients completed the questionnaires themselves. The QLQ-C30 has been developed by the EORTC.7 It is a multi-dimensional questionnaire consisting of nine scales: five are functional scales (physical, role, cognitive, emotional and social), three are symptom scales (fatigue, pain and nausea, and vomiting) and one is a global health status and quality of life scale. There are also six singleitem measures (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). A high score for a functional scale represents a high level of functioning, and a high score for the global health status and quality of life represents a high quality of life. On the other hand, a high score for a symptom scale or item represents a high level of symptomatology and problems. The QLQ-C30, also known as the core questionnaire, may be used for all cancer patients, but there are supplementary questionnaires (modules) specific to the cancer being studied. The QLQ-CR38 is the colorectal
cancer module,8 and is made up of 38 questions assessing disease symptoms, side-effects of treatment, body image, sexuality and future perspective. As with the QLQ-C30, a high score for a functional scale represents a high level of functioning, whilst a high score for a symptom scale or item represents a high level of symptomatology and problems. The SF-36 originated in America from the Medical Outcomes Study.9 It measures subjective health status or health-related quality of life, and has been designed to be self-administered. It consists of 36 items, measuring eight dimensions of health on multi-item scales. The eight dimensions measure physical functioning, social functioning, role limitations because of physical and emotional problems, mental health, energy and vitality, body pain and general health perception. The scoring scale ranges from 0 to 100, with lower scores indicating worse health. For this study we used the SF-36 version 2 (SF36 II, also known as the international version) which has an improved layout, wording and scaling, as well as improved reliability over the original version of the SF36.10,11 The study was approved by the Tayside committee on Medical Research Ethics and the Highland Health Board Ethics Committee.
Statistical analysis Results are expressed as mean (standard deviation) and median (interquartile range). The non-parametric Wilcoxon signed-rank test for matched samples was used to compare the scores of the patients with tumour recurrence to those of the matched group with no recurrence. A subgroup analysis was also performed, using a Mann–Whitney U-test, comparing the quality of life scores of patients with local recurrence to the scores of patients with distant recurrence. A 2% level
RECURRENT RECTAL CANCER AND QUALITY OF LIFE
351
Table 2 Comparison of the EORTC QLQ-C30 scores of patients with tumour recurrence and the scores of matched patients with no recurrence (Wilcoxon signed rank test) No recurrence Quality of life dimensions PF RF EF CF SF QOL FAT N/V PAIN DYSP INSOM APP CONS DIAR FINANCE
Mean (standard deviation) 80.0 78.0 83.3 88.0 78.7 70.0 22.4 5.0 19.3 16.0 21.3 8.0 10.0 12.7 11.3
(22.5) (26.4) (21.7) (17.8) (27.1) (20.8) (20.7) (10.7) (25.5) (25.4) (24.1) (17.2) (19.3) (23.2) (25.7)
Median (interquartile range) 80.0 83.3 91.7 100.0 83.3 75.0 22.2 0.0 0.0 0.0 16.7 0.0 0.0 0.0 0.0
(60.0, 100.0) (66.7, 100.0) (75.0, 100.0) (83.3, 100.0) (66.7, 100.0) (58.3, 83.3) (0.0, 33.3) (0.0, 0.0) (0.0, 33.3) (0.0, 33.3) (0.0, 33.3) (0.0, 0.0) (0.0, 9.1) (0.0, 33.3) (0.0, 0.0)
Tumour recurrence Mean (standard deviation) 56.8 51.3 68.0 76.7 56.0 47.3 47.1 11.3 42.7 34.7 37.3 25.3 16.0 16.0 14.7
(29.5) (32.3) (22.4) (20.2) (32.9) (26.1) (34.9) (14.8) (31.9) (32.2) (36.0) (27.4) (25.4) (23.5) (23.5)
Median (interquartile range)
z
P-value
60.0 (40.0, 80.0) 60.0 (33.3, 83.3) 66.7 (50.0, 85.4) 66.7 (66.7, 100.0) 66.7 (16.7, 83.3) 50.0 (25.0, 66.7) 55.6 (19.4, 77.8) 0.0 (0.0, 16.7) 50.0 (12.5, 66.7) 33.3 (0.0, 66.7) 33.3 (0.0, 41.7) 33.3 (0.0, 41.7) 0.0 (0.0, 33.3) 0.0 (0.0, 33.3) 0.0 (0.0, 33.3)
3.458 3.465 3.244 3.089 3.419 4.015 −3.459 −2.071 −3.321 −2.692 −2.110 −3.097 −1.346 −0.910 −0.760
0.001 0.001 0.001 0.002 0.001 0.0001 0.001 0.038 0.001 0.007 0.035 0.002 0.18 0.36 0.45
Abbreviations: PF, physical function; RF, role function; EF, emotional function; CF, cognitive function; SF, social function; QOL, global quality of life score; FAT, fatigue; N/V, nausea and vomiting; DYSP, dyspnoea; INSOM, insomnia; APP, appetite; CONS, constipation; DIAR, diarrhoea; FINANCE, financial problems.
Table 3 Comparison of the EORTC QLQ-CR38 scores of patients with tumour recurrence to the scores of matched patients with no recurrence (Wilcoxon signed-rank test) No recurrence Quality of life dimensions MIC GIT WL FU IMAGE SX DEF STO
Mean (standard deviation) 20.9 18.0 10.0 71.3 79.6 20.33 20.3 28.1
(17.2) (16.2) (24.5) (22.3) (26.5) (23.3) (17.8) (19.6)
Median (interquartile range) 22.2 13.3 0.0 66.7 88.9 8.33 14.2 23.8
(11.1, 33.3) (6.7, 21.7) (0.0, 0.0) (66.7, 100.0) (75.0, 100.0) (0.0, 37.5) (9.5, 28.6) (14.3, 38.1)
Tumour recurrence Mean (standard deviation) 24.4 25.3 26.7 49.3 63.1 9.33 30.0 28.6
(14.9) (18.7) (32.9) (23.6) (24.5) (13.5) (11.5) (18.4)
Median (interquartile range) 22.2 20.0 0.0 66.7 66.7 0.0 23.8 23.8
(11.1, 33.3) (6.7, 40.0) (0.0, 66.7) (33.3, 66.7) (52.8, 77.8) (0.0, 16.7) (19.0, 33.3) (19.0, 23.6)
z
P-value
−1.435 −2.011 −2.458 3.693 2.859 2.616 −0.537 −0.689
0.15 0.044 0.014 0.0001 0.004 0.009 0.59 0.49
Abbreviations: MIC, micturition problems; GIT, gastrointestinal tract problems; WL, weight loss; IMAGE, body image perception; SX, sexual function; FU, future perspective; DEF, defaecation problems; STO, stoma-related problems.
of statistical significance was chosen (P<0.02) to reduce the risk of type I errors arising from multiple testing. All statistical analyses were carried out using SPSS 9.0 (Chicago, USA).
RESULTS The results are shown in Tables 2, 3 and 4. The quality of life scores of patients with tumour recurrence were significantly lower, for most dimensions, than those of the matched sample of patients who were considered to
be free of cancer. There were no measurable differences, however, in the Nausea and Vomiting and Financial Problems scores on the QLQ-C30, nor in the Micturition symptoms, Gastrointestinal symptoms, Defaecation problems and Stoma problems on the QLQ-CR38. Subgroup analysis showed that the Gastrointestinal symptoms scores (QLQ-CR38) were worse in patients with local recurrence when compared to those with distant recurrence (median scores 33.3 vs 10.0, P= 0.02, Mann–Whitney U-test). There were however no measurable differences in the scores of the other quality
352
J. CAMILLERI-BRENNAN AND R. J. C. STEELE
Table 4 Comparison of the SF36 II scores of patients with tumour recurrence to the scores of matched patients with no recurrence (Wilcoxon signed-rank test) No recurrence Quality of life dimensions
Mean (standard deviation)
PF RP RE SF MH EV BP GHP
63.3 64.9 82.5 73.8 77.1 59.9 74.9 63.7
(26.7) (31.7) (25.7) (28.9) (15.9) (18.8) (29.1) (23.5)
Tumour recurrence
Median (interquartile range) 52.5 35.9 75.0 50.0 65.0 50.0 52.8 46.5
(72.5, (75.0, (91.7, (75.0, (80.0, (56.3, (88.9, (67.0,
85.0) 95.3) 100.0) 100.0) 90.0) 75.0) 100.0) 83.3)
Mean (standard deviation) 47.4 38.5 56.3 46.0 62.8 39.8 55.1 38.2
(27.6) (34.2) (33.5) (33.1) (20.6) (27.1) (33.1) (22.3)
Median (interquartile range) 20.0 12.5 33.3 25.0 43.8 17.2 22.2 23.8
(45.0, (25.0, (50.0, (37.5, (60.0, (37.5, (55.6, (35.0,
76.3) 75.0) 83.3) 75.0) 81.3) 75.0) 88.9) 49.5)
z
P-value
2.685 2.938 4.148 3.484 3.657 3.401 2.820 3.981
0.007 0.003 0.0001 0.0001 0.0001 0.001 0.005 0.0001
Abbreviations: physical functioning (PF), social functioning (SF), role limitations because of physical and emotional problems (RP and RE), mental health (MH), energy and vitality (EV), body pain (BP) and general health perception (GHP).
of life dimensions, including the global quality of life scores on the QLQ-C30. The answers on male sexual problems, female sexual problems and sexual enjoyment were not analysed statistically because of the high number of missing answers. The item on sexual enjoyment was only answered by 16 of 75 patients. Only four of 27 female patients answered the items on female sexual problems, and 29 of 48 males responded to the questions on male sexual problems.
DISCUSSION These results show that patients who had recurrent rectal cancer had a lower quality of life than patients who were considered to have been cured. The differences in quality of life were present in most quality of life dimensions, when using both the SF36 II as well as the EORTC QLQ-C30 and QLQ-CR38 questionnaires. Thus, patients with recurrent disease suffer not only from physical distress, but their social and psychological wellbeing is also poor. Sexual function of patients with recurrent rectal cancer was significantly poorer than those with no tumour recurrence. However, analysis of the nature of the sexual problems experienced by these patients was not possible because of lack of response to the relevant questions, especially in females. The sexual health of patients with recurrent rectal cancer thus merits further study. In view of the poor quality of life experienced by patients with recurrent cancer, a number of issues should be addressed. Primarily, efforts should be directed at preventing recurrence of rectal cancer. This means meticulous surgery (careful mesorectal excision)12 and adjuvant therapy if necessary in accordance with the results of current trials.13–15 Another issue is the specific treatment of the recurrent
tumour. Sagar and Pemberton advocated the use of radical pelvic surgery to improve both survival and quality of life in selected patients with locally recurrent cancer.3 There is however an operative morbidity rate of 10% to 44% and an operative mortality rate of 0 to 8.5% associated with exenterative surgery. Pre-operative radiotherapy, intraoperative radiotherapy and brachytherapy have been used as adjuncts to surgery, although it is not known whether this adjuvant treatment confers any additional quality of life benefits.3,16 Advances in the treatment of distant metastatic disease by chemotherapy, of bone metastases by radiotherapy and of liver metastases by cryotherapy or radiofrequency ablation may relieve the patient of his disease.17 The side-effects of these measures may however potentially worsen quality of life,18 and future studies on the treatment of recurrent disease must take this into account. Radical surgery and chemotherapy for tumour recurrence is certainly not appropriate for many patients. For these, palliative care is necessary.17 Pain relief is a high priority, but other aspects of a patient’s quality of life must be taken into account. It is important that, when dealing with the physical aspect of the recurrent disease, the social and psychological needs of the patients are not ignored. These patients should be helped to achieve a satisfactory level of adjustment and adaptation, and support groups are invaluable for these patients and their families.
ACKNOWLEDGEMENTS The authors would like to thank the following: Mr S. Ogston, Statistician in the Department of Epidemiology and Public Health, University of Dundee, for advice on statistical analysis. Mrs C. van Pottelsberghe from the EORTC datacentre in Brussels for permission to use the
RECURRENT RECTAL CANCER AND QUALITY OF LIFE QLQ-C30 questionnaire. Dr Mirjam Sprangers from the University of Amsterdam for permission to use the QLQCR38 questionnaire. Dr Mark Kosinski for permission to use the SF36 II questionnaire, Mr A. Munro, Consultant Surgeon, Raigmore Hospital, Inverness, Scotland ConvaTec (Europe) and Tenovus (Scotland) for financial support of the study.
353
8. 9. 10. 11.
REFERENCES 1. Karanjia ND, Schache DJ, North WRS, Heald RJ. ‘Close shave’ in anterior resection. Br J Surg 1990; 77: 510–2. 2. Adloff M, Arnaud JP, Schloegel M, Thibaud D. Factors influencing local recurrence after abdominoperineal resection for cancer of the rectum. Dis Colon Rectum 1985; 28: 413–5. 3. Sagar PM, Pemberton JH. Surgical management of locally recurrent rectal cancer. Br J Surg 1996; 83: 293–304. 4. Bull AA, Meyerowitz BE, Hart S et al. Quality of life of women with recurrent breast cancer. Breast Cancer Res Treat 1999; 54: 47–57. 5. Ware JE, Snow KK, Kosinski M. SF36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, 1993. 6. Carstairs V, Morris R. Deprivation and Health in Scotland. Aberdeen: Aberdeen University Press, 1991. 7. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A. The European Organisation for Research and Treatment of Cancer QLQ-C30: a quality of life instrument for
12. 13. 14. 15. 16. 17. 18.
use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365–76. Sprangers MA, te Velde A, Aaronson NK. The construction and testing of the EORTC Colorectal Cancer-specific quality of life questionnaire module (QLQ-CR38). Eur J Cancer 1999; 35: 238–47. Ware J, Sherbourne C. The MOS 36-item Short-Form Health Survey 1: conceptual framework and item selection. Med Care 1992; 30: 473–83. Ware JE, Kosinski M. Improvement in the content and scoring of the SF-36 Health Survey Version 2. (SF-36 web site at http:// www.sf-36.com/news/sf36-20.html). Jenkinson C, Stewart-Brown S, Petersen S, Paice C. Assessment of the SF-36 version 2 in the United Kingdom. J Epidemiol Community Health 1999; 53: 46–50. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986; i: 1478–82. Stamatakis J, Steele RJC. Adjuvant therapy for colorectal cancer. Br J Hosp Med 1995; 54: 259–63. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 1997; 336: 980–7. Steele RJC, Sebag-Montefiore D. Adjuvant radiotherapy for rectal cancer. Br J Surg 1999; 86: 1233–4. Goes RN, Beart RW, Simons AJ, Gunderson LL, Grado G, Streeter O. Use of brachytherapy in management of locally recurrent rectal cancer. Dis Colon Rectum 1997; 40: 1177–9. De Cosse JJ, Cennerazzo RN. Quality of life management of patients with colorectal cancer. CA Cancer J Clin 1997; 47: 198–206. Fallowfield L. The Quality of Life: the Missing Measurement in Health Care. London: Souvenir Press, 1990.
Accepted for publication 18 January 2001
The impact of recurrent rectal cancer on quality of life J. Camilleri-Brennan and R. J. C. Steele University Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, Scotland
Aims: To determine, in patients operated upon for rectal cancer, the impact that tumour recurrence has on quality of life. Methods: Twenty-five patients, who had curative surgery for rectal cancer from 1992 to 1997, and who subsequently developed tumour recurrence, participated. Each patient was individually matched with two patients who also had rectal cancer surgery during the same period of time but were considered to be free of cancer. The patients were matched for age, gender, type of operation and socioeconomic status. They answered the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and CR38 quality of life questionnaires, as well as the SF36 II questionnaire, at least 1 year after surgery. Results: Patients with recurrent rectal cancer had significantly lower quality of life scores than cured patients in most dimensions, as measured by the three questionnaires. A significant difference was also seen in the global quality of life score on the QLQ-C30 (median scores 50 vs 75, z=4.015, P=0.0001). Conclusion: Recurrence of rectal cancer has a profound effect on quality of life, affecting most measurable dimensions. Treatment of recurrent cancer should not only be directed at the physical aspect of the disease, but also at its psychological and social aspects. 2001 Harcourt Publishers Ltd Key words: quality of life; rectal cancer; recurrent cancer; surgery.
INTRODUCTION Recurrence of rectal cancer after potentially curative surgery is a major problem. Tumour recurrence may be local, that is within the pelvis, or distant, commonly in the liver. The incidence of tumour recurrence varies from centre to centre. This is particularly true of local recurrence which has been reported to be as low as 2.6%1 and as high as 31.8%.2 Most of the tumours recur within the first 2 years post-operatively. Recurrent rectal cancer carries a high morbidity and a poor prognosis,3 and it is likely that the presence of recurrent rectal cancer leads to a poor quality of life. A study on patients with recurrent breast cancer showed that the quality of life of these patients was poor,4 but no formal quality of life studies have been carried out in patients with recurrent rectal cancer. It is not known which quality of life dimensions are affected, and to what extent the patients’ quality of life is impaired. The aim of this study was to measure the impact of
Correspondence to: Mr John Camilleri-Brennan FRCS, University Department of Surgery and Molecular Oncology, Level 6, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland. Tel: +44 (0)1382 660111; Fax: +44 (0)1382 641795; E-mail: [email protected] 0748–7983/01/040349+05 $35.00/0
recurrent tumour on patients’ quality of life using wellvalidated and reliable quality of life questionnaires. A comparison was made between patients with tumour recurrence and a matched group of patients with no evidence of recurrent local or metastatic rectal cancer who had been operated upon within the same time period.
PATIENTS AND METHODS Hospital records were used to identify patients who had primary curative surgery for rectal cancer from 1992 to 1997 at four hospitals in Scotland (Raigmore Hospital, Inverness; Ninewells Hospital, Dundee; Perth Royal Infirmary, Perth; Stracathro Infirmary, Brechin) and who were subsequently diagnosed with tumour recurrence after surgery. Local tumour recurrence was diagnosed radiologically and, in patients who had an anterior resection, using endoscopy and histological examination of biopsies. Distant tumour recurrence was diagnosed by rising carcinoembryonic antigen (CEA) and the presence of metastases on liver ultrasound and/or CT scan. Thirty patients who were alive with recurrent rectal cancer were identified and invited to participate in the study. Twenty-five of these patients agreed to participate. 2001 Harcourt Publishers Ltd
350
J. CAMILLERI-BRENNAN AND R. J. C. STEELE
Table 1 Demographic and clinical characteristics of participants Patients with tumour recurrence
Matched patients without tumour recurrence
25 64 (49–80) 16 9 5 16 4 14 11 6 (5–15) 24 (12–59)
50 67 (45–84) 32 18 11 33 6 28 22 7 (3–15) 22 (11–72)
Number Age∗ (years) Male Female Depcat 1 and 2 Depcat 3, 4 and 5 Depcat 6 and 7 APER Anterior resection Level of anastomosis† (cm) Months post-operatively‡
Abbreviations: Depcat, Deprivation Category; APER, abdominoperineal resection. ∗ Age expressed as median and range. † Level of anastomosis was measured in patients who had an anterior resection; values are expressed as median and range. ‡ Months post-operatively expressed as median and range.
Eleven had a local recurrence, 12 had distant metastases and two had both local and distant recurrence. Each patient with tumour recurrence was individually matched with two tumour-free patients for age (within 4 years of each other), gender, type of operation (abdominoperineal resection or anterior resection), and socioeconomic status (Table 1). Age, gender and socioeconomic status have been shown to have a significant effect on quality of life.5 Socioeconomic status (Deprivation Category) was determined using the Carstairs Index, an index of deprivation based on the postcode.6 The median time since surgery was similar in both groups. All patients were given the following quality of life questionnaires: the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and the Medical Outcomes Study ShortForm 36 version 2 (SF36 II). The patients completed the questionnaires themselves. The QLQ-C30 has been developed by the EORTC.7 It is a multi-dimensional questionnaire consisting of nine scales: five are functional scales (physical, role, cognitive, emotional and social), three are symptom scales (fatigue, pain and nausea, and vomiting) and one is a global health status and quality of life scale. There are also six singleitem measures (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). A high score for a functional scale represents a high level of functioning, and a high score for the global health status and quality of life represents a high quality of life. On the other hand, a high score for a symptom scale or item represents a high level of symptomatology and problems. The QLQ-C30, also known as the core questionnaire, may be used for all cancer patients, but there are supplementary questionnaires (modules) specific to the cancer being studied. The QLQ-CR38 is the colorectal
cancer module,8 and is made up of 38 questions assessing disease symptoms, side-effects of treatment, body image, sexuality and future perspective. As with the QLQ-C30, a high score for a functional scale represents a high level of functioning, whilst a high score for a symptom scale or item represents a high level of symptomatology and problems. The SF-36 originated in America from the Medical Outcomes Study.9 It measures subjective health status or health-related quality of life, and has been designed to be self-administered. It consists of 36 items, measuring eight dimensions of health on multi-item scales. The eight dimensions measure physical functioning, social functioning, role limitations because of physical and emotional problems, mental health, energy and vitality, body pain and general health perception. The scoring scale ranges from 0 to 100, with lower scores indicating worse health. For this study we used the SF-36 version 2 (SF36 II, also known as the international version) which has an improved layout, wording and scaling, as well as improved reliability over the original version of the SF36.10,11 The study was approved by the Tayside committee on Medical Research Ethics and the Highland Health Board Ethics Committee.
Statistical analysis Results are expressed as mean (standard deviation) and median (interquartile range). The non-parametric Wilcoxon signed-rank test for matched samples was used to compare the scores of the patients with tumour recurrence to those of the matched group with no recurrence. A subgroup analysis was also performed, using a Mann–Whitney U-test, comparing the quality of life scores of patients with local recurrence to the scores of patients with distant recurrence. A 2% level
RECURRENT RECTAL CANCER AND QUALITY OF LIFE
351
Table 2 Comparison of the EORTC QLQ-C30 scores of patients with tumour recurrence and the scores of matched patients with no recurrence (Wilcoxon signed rank test) No recurrence Quality of life dimensions PF RF EF CF SF QOL FAT N/V PAIN DYSP INSOM APP CONS DIAR FINANCE
Mean (standard deviation) 80.0 78.0 83.3 88.0 78.7 70.0 22.4 5.0 19.3 16.0 21.3 8.0 10.0 12.7 11.3
(22.5) (26.4) (21.7) (17.8) (27.1) (20.8) (20.7) (10.7) (25.5) (25.4) (24.1) (17.2) (19.3) (23.2) (25.7)
Median (interquartile range) 80.0 83.3 91.7 100.0 83.3 75.0 22.2 0.0 0.0 0.0 16.7 0.0 0.0 0.0 0.0
(60.0, 100.0) (66.7, 100.0) (75.0, 100.0) (83.3, 100.0) (66.7, 100.0) (58.3, 83.3) (0.0, 33.3) (0.0, 0.0) (0.0, 33.3) (0.0, 33.3) (0.0, 33.3) (0.0, 0.0) (0.0, 9.1) (0.0, 33.3) (0.0, 0.0)
Tumour recurrence Mean (standard deviation) 56.8 51.3 68.0 76.7 56.0 47.3 47.1 11.3 42.7 34.7 37.3 25.3 16.0 16.0 14.7
(29.5) (32.3) (22.4) (20.2) (32.9) (26.1) (34.9) (14.8) (31.9) (32.2) (36.0) (27.4) (25.4) (23.5) (23.5)
Median (interquartile range)
z
P-value
60.0 (40.0, 80.0) 60.0 (33.3, 83.3) 66.7 (50.0, 85.4) 66.7 (66.7, 100.0) 66.7 (16.7, 83.3) 50.0 (25.0, 66.7) 55.6 (19.4, 77.8) 0.0 (0.0, 16.7) 50.0 (12.5, 66.7) 33.3 (0.0, 66.7) 33.3 (0.0, 41.7) 33.3 (0.0, 41.7) 0.0 (0.0, 33.3) 0.0 (0.0, 33.3) 0.0 (0.0, 33.3)
3.458 3.465 3.244 3.089 3.419 4.015 −3.459 −2.071 −3.321 −2.692 −2.110 −3.097 −1.346 −0.910 −0.760
0.001 0.001 0.001 0.002 0.001 0.0001 0.001 0.038 0.001 0.007 0.035 0.002 0.18 0.36 0.45
Abbreviations: PF, physical function; RF, role function; EF, emotional function; CF, cognitive function; SF, social function; QOL, global quality of life score; FAT, fatigue; N/V, nausea and vomiting; DYSP, dyspnoea; INSOM, insomnia; APP, appetite; CONS, constipation; DIAR, diarrhoea; FINANCE, financial problems.
Table 3 Comparison of the EORTC QLQ-CR38 scores of patients with tumour recurrence to the scores of matched patients with no recurrence (Wilcoxon signed-rank test) No recurrence Quality of life dimensions MIC GIT WL FU IMAGE SX DEF STO
Mean (standard deviation) 20.9 18.0 10.0 71.3 79.6 20.33 20.3 28.1
(17.2) (16.2) (24.5) (22.3) (26.5) (23.3) (17.8) (19.6)
Median (interquartile range) 22.2 13.3 0.0 66.7 88.9 8.33 14.2 23.8
(11.1, 33.3) (6.7, 21.7) (0.0, 0.0) (66.7, 100.0) (75.0, 100.0) (0.0, 37.5) (9.5, 28.6) (14.3, 38.1)
Tumour recurrence Mean (standard deviation) 24.4 25.3 26.7 49.3 63.1 9.33 30.0 28.6
(14.9) (18.7) (32.9) (23.6) (24.5) (13.5) (11.5) (18.4)
Median (interquartile range) 22.2 20.0 0.0 66.7 66.7 0.0 23.8 23.8
(11.1, 33.3) (6.7, 40.0) (0.0, 66.7) (33.3, 66.7) (52.8, 77.8) (0.0, 16.7) (19.0, 33.3) (19.0, 23.6)
z
P-value
−1.435 −2.011 −2.458 3.693 2.859 2.616 −0.537 −0.689
0.15 0.044 0.014 0.0001 0.004 0.009 0.59 0.49
Abbreviations: MIC, micturition problems; GIT, gastrointestinal tract problems; WL, weight loss; IMAGE, body image perception; SX, sexual function; FU, future perspective; DEF, defaecation problems; STO, stoma-related problems.
of statistical significance was chosen (P<0.02) to reduce the risk of type I errors arising from multiple testing. All statistical analyses were carried out using SPSS 9.0 (Chicago, USA).
RESULTS The results are shown in Tables 2, 3 and 4. The quality of life scores of patients with tumour recurrence were significantly lower, for most dimensions, than those of the matched sample of patients who were considered to
be free of cancer. There were no measurable differences, however, in the Nausea and Vomiting and Financial Problems scores on the QLQ-C30, nor in the Micturition symptoms, Gastrointestinal symptoms, Defaecation problems and Stoma problems on the QLQ-CR38. Subgroup analysis showed that the Gastrointestinal symptoms scores (QLQ-CR38) were worse in patients with local recurrence when compared to those with distant recurrence (median scores 33.3 vs 10.0, P= 0.02, Mann–Whitney U-test). There were however no measurable differences in the scores of the other quality
352
J. CAMILLERI-BRENNAN AND R. J. C. STEELE
Table 4 Comparison of the SF36 II scores of patients with tumour recurrence to the scores of matched patients with no recurrence (Wilcoxon signed-rank test) No recurrence Quality of life dimensions
Mean (standard deviation)
PF RP RE SF MH EV BP GHP
63.3 64.9 82.5 73.8 77.1 59.9 74.9 63.7
(26.7) (31.7) (25.7) (28.9) (15.9) (18.8) (29.1) (23.5)
Tumour recurrence
Median (interquartile range) 52.5 35.9 75.0 50.0 65.0 50.0 52.8 46.5
(72.5, (75.0, (91.7, (75.0, (80.0, (56.3, (88.9, (67.0,
85.0) 95.3) 100.0) 100.0) 90.0) 75.0) 100.0) 83.3)
Mean (standard deviation) 47.4 38.5 56.3 46.0 62.8 39.8 55.1 38.2
(27.6) (34.2) (33.5) (33.1) (20.6) (27.1) (33.1) (22.3)
Median (interquartile range) 20.0 12.5 33.3 25.0 43.8 17.2 22.2 23.8
(45.0, (25.0, (50.0, (37.5, (60.0, (37.5, (55.6, (35.0,
76.3) 75.0) 83.3) 75.0) 81.3) 75.0) 88.9) 49.5)
z
P-value
2.685 2.938 4.148 3.484 3.657 3.401 2.820 3.981
0.007 0.003 0.0001 0.0001 0.0001 0.001 0.005 0.0001
Abbreviations: physical functioning (PF), social functioning (SF), role limitations because of physical and emotional problems (RP and RE), mental health (MH), energy and vitality (EV), body pain (BP) and general health perception (GHP).
of life dimensions, including the global quality of life scores on the QLQ-C30. The answers on male sexual problems, female sexual problems and sexual enjoyment were not analysed statistically because of the high number of missing answers. The item on sexual enjoyment was only answered by 16 of 75 patients. Only four of 27 female patients answered the items on female sexual problems, and 29 of 48 males responded to the questions on male sexual problems.
DISCUSSION These results show that patients who had recurrent rectal cancer had a lower quality of life than patients who were considered to have been cured. The differences in quality of life were present in most quality of life dimensions, when using both the SF36 II as well as the EORTC QLQ-C30 and QLQ-CR38 questionnaires. Thus, patients with recurrent disease suffer not only from physical distress, but their social and psychological wellbeing is also poor. Sexual function of patients with recurrent rectal cancer was significantly poorer than those with no tumour recurrence. However, analysis of the nature of the sexual problems experienced by these patients was not possible because of lack of response to the relevant questions, especially in females. The sexual health of patients with recurrent rectal cancer thus merits further study. In view of the poor quality of life experienced by patients with recurrent cancer, a number of issues should be addressed. Primarily, efforts should be directed at preventing recurrence of rectal cancer. This means meticulous surgery (careful mesorectal excision)12 and adjuvant therapy if necessary in accordance with the results of current trials.13–15 Another issue is the specific treatment of the recurrent
tumour. Sagar and Pemberton advocated the use of radical pelvic surgery to improve both survival and quality of life in selected patients with locally recurrent cancer.3 There is however an operative morbidity rate of 10% to 44% and an operative mortality rate of 0 to 8.5% associated with exenterative surgery. Pre-operative radiotherapy, intraoperative radiotherapy and brachytherapy have been used as adjuncts to surgery, although it is not known whether this adjuvant treatment confers any additional quality of life benefits.3,16 Advances in the treatment of distant metastatic disease by chemotherapy, of bone metastases by radiotherapy and of liver metastases by cryotherapy or radiofrequency ablation may relieve the patient of his disease.17 The side-effects of these measures may however potentially worsen quality of life,18 and future studies on the treatment of recurrent disease must take this into account. Radical surgery and chemotherapy for tumour recurrence is certainly not appropriate for many patients. For these, palliative care is necessary.17 Pain relief is a high priority, but other aspects of a patient’s quality of life must be taken into account. It is important that, when dealing with the physical aspect of the recurrent disease, the social and psychological needs of the patients are not ignored. These patients should be helped to achieve a satisfactory level of adjustment and adaptation, and support groups are invaluable for these patients and their families.
ACKNOWLEDGEMENTS The authors would like to thank the following: Mr S. Ogston, Statistician in the Department of Epidemiology and Public Health, University of Dundee, for advice on statistical analysis. Mrs C. van Pottelsberghe from the EORTC datacentre in Brussels for permission to use the
RECURRENT RECTAL CANCER AND QUALITY OF LIFE QLQ-C30 questionnaire. Dr Mirjam Sprangers from the University of Amsterdam for permission to use the QLQCR38 questionnaire. Dr Mark Kosinski for permission to use the SF36 II questionnaire, Mr A. Munro, Consultant Surgeon, Raigmore Hospital, Inverness, Scotland ConvaTec (Europe) and Tenovus (Scotland) for financial support of the study.
353
8. 9. 10. 11.
REFERENCES 1. Karanjia ND, Schache DJ, North WRS, Heald RJ. ‘Close shave’ in anterior resection. Br J Surg 1990; 77: 510–2. 2. Adloff M, Arnaud JP, Schloegel M, Thibaud D. Factors influencing local recurrence after abdominoperineal resection for cancer of the rectum. Dis Colon Rectum 1985; 28: 413–5. 3. Sagar PM, Pemberton JH. Surgical management of locally recurrent rectal cancer. Br J Surg 1996; 83: 293–304. 4. Bull AA, Meyerowitz BE, Hart S et al. Quality of life of women with recurrent breast cancer. Breast Cancer Res Treat 1999; 54: 47–57. 5. Ware JE, Snow KK, Kosinski M. SF36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, 1993. 6. Carstairs V, Morris R. Deprivation and Health in Scotland. Aberdeen: Aberdeen University Press, 1991. 7. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A. The European Organisation for Research and Treatment of Cancer QLQ-C30: a quality of life instrument for
12. 13. 14. 15. 16. 17. 18.
use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365–76. Sprangers MA, te Velde A, Aaronson NK. The construction and testing of the EORTC Colorectal Cancer-specific quality of life questionnaire module (QLQ-CR38). Eur J Cancer 1999; 35: 238–47. Ware J, Sherbourne C. The MOS 36-item Short-Form Health Survey 1: conceptual framework and item selection. Med Care 1992; 30: 473–83. Ware JE, Kosinski M. Improvement in the content and scoring of the SF-36 Health Survey Version 2. (SF-36 web site at http:// www.sf-36.com/news/sf36-20.html). Jenkinson C, Stewart-Brown S, Petersen S, Paice C. Assessment of the SF-36 version 2 in the United Kingdom. J Epidemiol Community Health 1999; 53: 46–50. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986; i: 1478–82. Stamatakis J, Steele RJC. Adjuvant therapy for colorectal cancer. Br J Hosp Med 1995; 54: 259–63. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 1997; 336: 980–7. Steele RJC, Sebag-Montefiore D. Adjuvant radiotherapy for rectal cancer. Br J Surg 1999; 86: 1233–4. Goes RN, Beart RW, Simons AJ, Gunderson LL, Grado G, Streeter O. Use of brachytherapy in management of locally recurrent rectal cancer. Dis Colon Rectum 1997; 40: 1177–9. De Cosse JJ, Cennerazzo RN. Quality of life management of patients with colorectal cancer. CA Cancer J Clin 1997; 47: 198–206. Fallowfield L. The Quality of Life: the Missing Measurement in Health Care. London: Souvenir Press, 1990.
Accepted for publication 18 January 2001