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ORIGINAL ARTICLES |
From the Departments of Surgery (TA, CJ, RT), Radiation Therapy (JA), and Hematology-Oncology (SS-V), The University of Texas Southwestern Medical Center, and the Veterans Affairs North Texas Health Care System, Dallas, Texas.
Correspondence: Address correspondence and reprint requests to: Dr. Thomas Anthony, Assistant Professor of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9161; Fax: 214-648-7965.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: All participating patients had completed therapy at least 6 months before enrollment. One hundred fifty-eight patients were accrued over a 3-year period (January 1, 1997 to December 31, 1999) at a single institution. The impact of CRC surgery on HRQL was measured by comparing a cohort of 61 patients undergoing surgery alone for the treatment of CRC (CRC-S group) with 44 patients undergoing surgery for benign colonic disease (BCD group). To study the effect of adjuvant therapy for CRC on HRQL, a third cohort of 53 patients undergoing both surgical and adjuvant treatment (CRC-S/A group) was compared with the CRC-S group. For each group, health status was measured by a health survey questionnaire, SHORT FORM 36 (SF36). For patients treated for CRC, an additional disease-specific supplemental questionnaire also was used.
RESULTS: Self-reported health status, as measured by mean SF36 score, was significantly reduced for the BCD group compared with CRC-S patients on general health perception (41.9 ± 3.9 vs. 52.2 ± 3.0, P = .04) and the standardized physical component score (31.2 ± 1.7 vs. 37.5 ± 1.5, P < .005). Despite an increased number of distally located tumors, later stage cancers, and an increased number of recurrences in the CRC-S/A group compared with the CRC-S cohort, no significant differences were identified between these groups on any of the subscales or standardized scores of SF36. Using the supplemental questions, no differences were identified between the CRC groups with respect to appetite, weight, or gastrointestinal or urinary functioning.
CONCLUSIONS: Surgical therapy for CRC probably has minimal impact on long-term HRQL when compared with surgery for benign colonic processes. Similarly, there does not appear to be a measurable, lasting impact of CRC adjuvant therapy on HRQL when compared with surgery alone. Although overall impact of therapies for CRC on HRQL appears to be limited, measurement of therapeutic influence on an individual level and identification of selection criteria based on estimated impact on HRQL for these therapies requires prospective validation.
Key Words: Colorectal cancer— • Health-related quality of life— • Treatment.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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This study was undertaken to provide information on the long-term effects of treatment for resectable CRC on HRQL. Specifically, the aims of this study were to define the impact that surgery for resectable CRC has on HRQL compared with surgery for benign colorectal disease and, secondly, to ascertain differences in HRQL for CRC patients based on adjuvant treatment.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Study Design
A case-control design was used to test the hypothesis that therapy used to treat colorectal cancer has a measurable long-term impact on HRQL. Three cohorts were evaluated in this study. To study the effects of surgery on HRQL for patients with CRC, patients undergoing surgery alone for CRC (CRC-S) were compared with patients undergoing surgery for benign colonic disease (BCD). To examine the effects of adjuvant therapy, CRC patients treated by surgery and adjuvant therapy (CRC-S/A) were compared with the CRC-S group.
Demographic and Perioperative Data
To be included in this study, all participants had to have completed therapy at least 6 months before enrollment. Patients were identified during the course of routine posttreatment surveillance visits. Inclusion criteria for patients with CRC included complete resection of all visible disease, including metastases. Medical records and a computerized database were used to determine age at diagnosis, location of the primary tumor, American Society of Anesthesiology (ASA) class (ASA class is a 5-category preoperative classification system correlated with perioperative mortality), and the time elapsed since the completion of therapy. For those patients in the CRC cohorts, the location and stage of the tumor, type of adjuvant therapy, and the presence of recurrence were recorded. For patients with multiple tumors, the location of the disease and staging were recorded according to the pathologically most advanced lesion. All patients who received any chemotherapy or radiation as part of the initial treatment of their CRC were included in the group receiving adjuvant therapy. Patients treated with either chemotherapy or radiotherapy for recurrent disease were classified according to their initial form of therapy.
Health-Related Quality of Life Assessment
Each patient participating in this study was given the Medical Outcomes Study Short Form-36 (SF36). For patients with CRC, SF36 was supplemented by five questions designed to investigate nutritional alterations and gastrointestinal or urinary dysfunction that might have occurred as a result of CRC therapy. The SF36 and the supplemental questions were self-administered at a scheduled, routine follow-up visit. Each test was administered only once.
The SF36 is a validated health survey consisting of 36 questions that measure 8 health concepts: physical functioning; role limitations due to physical problems; bodily pain; general health; vitality; social functioning; role limitations secondary to emotional problems; and mental health.8 Additionally, two summary scores are available: a standardized physical component and a standardized mental component. For each participant, a single number is derived from his or her responses to summarize each health concept.9 The scores are calibrated so that a higher score indicates an improved level of function. For example a higher score in the bodily pain category indicates less bodily pain, and a high score in social functioning indicates a higher level of social functioning.
Patients within both CRC groups were asked to complete a series of five supplemental questions designed to address specific potential concerns of patients who have completed therapy for CRC. These questions addressed appetite, weight, bowel and bladder habits, and satisfaction with treatment.
Statistical Analysis
All of the data are reported as mean ± standard error of the mean. All ANOVAs, Student’s t-tests, and Kruskal Wallis, Wilcoxon, and Fisher exact tests were performed using an 
= .05. A Bonferroni post hoc test was performed to examine pairwise group differences, and a Dunnett post hoc test was performed to examine multiple comparison (>2) when significant differences were detected. The calculations were performed using SAS statistical software (version 6.12, SAS Institute Inc., Cary, NC).
Estimating potential accrual from the population of CRC patients in our clinic we theorized that it would be possible to obtain 45 patients per arm of this study. Therefore, using 1-ß = .90 and = .05, our estimated sample size would be sufficient to identify a difference in mean values of health score of 0.7 standard deviations (e.g., a change in standardized physical score from 50 to 50 ± 7).
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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CRC-S/A group
The CRC-S/A group included 53 patients. Within the group treated by both surgery and adjuvant therapy, the average age of the patients was 64.8 years (range, 41–81 years). The median follow-up for this group was 24 months (range, 6–133 months). The mean ASA class for these patients was 2.8 (range, 2–4). Six patients (11%) were operated on emergently. A slight majority of patients in this group (27 of 52 [52%]) had tumors located proximal to the splenic flexure. One patient had synchronous cecal and sigmoid carcinomas. Recurrent disease was present in 15 of 53 patients (28%) at the time of the study. Most of the recurrences were in the patients whose initial tumor stage was III or IV (12 patients [80%]). Ten of 15 disease recurrences were noted in the first 2 years after the completion of initial therapy.
Of the 53 patients in the CRC-S/A group, 24 patients received chemotherapy alone (5-fluorouracil, [5-FU] and levamisole, 10 patients [42%]; 5-FU and leucovorin, 14 patients [58%]), 25 patients received chemotherapy in combination with external beam radiation (5-FU and leucovorin in each case), and 4 patients were treated with external beam radiation alone. For stage III colon cancers the duration of chemotherapy ranged from 1 to 12 months (median, 6 months). Twenty-nine patients with rectal cancer underwent external beam radiation as part of their therapy. The delivered dose of radiation varied from 3780 to 5400 cGy, with the majority of patients (17 of 29 [59%]) receiving 5040 cGy. Overall, 37 patients (70%) received the intended dose of radiation or the intended duration of chemotherapy.
BCD group
There were 44 patients in the control cohort, the BCD group, all of whom had undergone laparotomy for benign colonic conditions. The average age of these patients was 63.2 years (range, 41–81 years). The median time of survey completion following surgery was 26 months (range, 8–85 months). The indications for laparotomy were as follows: diverticulitis, 22 patients; lower GI bleeding, 9 patients; adenomatous polyps, 8 patients; and benign colonic obstruction, 5 patients. In 35 of 44 cases (80%), resection of disease involved removal of colon distal to the splenic flexure. In all cases of diverticulitis, only patients with one-stage operations were included. The average ASA class for these patients was 2.6 (range, 1–4), with 7 of 44 patients (16%) undergoing emergency operations. Table 1 compares the three groups with respect to demographic and perioperative variables.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Part of the difficulty in answering questions concerning the impact of therapy on HRQL has been the lack of a clear understanding of what constitutes "quality of life" and the correlate issue of how best to measure it. Although the methodology in the field of HRQL assessment is still evolving, it is generally accepted that HRQL incorporates three overlapping domains of functioning: physical, psychological, and social, as they relate to health status.4,8 Using this definition, survey instruments for assessment of HRQL should, at a minimum, measure health status in each of these areas. Furthermore, because physician assessment of patient quality of life is often inaccurate, eliciting individual patient response to HRQL and health status concerns is crucial.4,8,15 The SF36 fulfills these requirements and, additionally, has the benefits of widespread use, ease of administration and interpretation, and standardized scoring. We therefore chose the SF36 as our main survey instrument for this study. We also recognized that due to the generic nature of the questionnaire, it would be important to supplement SF36 with specific disease-related questions. Therefore, supplemental questions dealing with appetite, weight status, and gastrointestinal and urinary dysfunction were also asked of CRC patients included in this study.
The Effect of Type of Surgery on Health Status
A previous study had suggested that the more radical nature of the surgery required for extirpation of a cancer relative to benign processes would result in poorer HRQL.4 Other studies also had suggested that patients with surgically treated inflammatory bowel disease (IBD) had better sexual functioning and activity levels relative to patients undergoing therapy for CRC.4–6 Because IBD is a chronic condition associated with debilitating symptoms, we felt that inclusion of these patients would not be appropriate for comparison with CRC patients, who often are asymptomatic. We therefore chose a group of patients with benign colorectal disease, specifically excluding IBD, as a control group to compare with patients undergoing surgery for CRC to test the hypothesis that extent of surgery influenced HRQL.
The results of the present study suggest that HRQL actually is better in terms of physical component score and general health perception for patients undergoing surgical procedures for malignancies. A partial explanation for this finding may have been the trend toward more frequent emergency surgery in the BCD group. Subgroup analysis excluding all patients with emergency operations, however, continued to show a significant difference between the BCD and CRC groups with respect to the standardized physical component score. We speculate that patient expectations coupled with the context of the disease being treated may well be more important determinants of long-term health status than the actual surgical therapy rendered to treat that disease. Patients being treated for malignancy expect different quality-of-life outcomes compared with patients undergoing similar therapy for benign disease and, as a result, may report a more optimistic assessment of their posttreatment quality of life. This phenomenon has been referred to as "reframing" and is thought to be part of the patients’ adaptation to their disease and its treatment.16
The Effect of CRC Adjuvant Therapy on Health Status
Neither SF36 nor the supplemental questions used in this study identified a difference in health status as a function of adjuvant therapy. The lack of difference between the two CRC groups was unexpected given the biases in the CRC-S/A group: more distally located cancer, more late stage (AJCC Stage III and IV) disease, and a greater number of recurrences. Intuitively, each of these factors would be thought to incur a poorer quality of life. One other study has reported a similar lack of influence of adjuvant therapy on HRQL. Zaniboni and colleagues17 reported the large GIVIO-SITAC-01 (Gruppo Italiano Valutazione Interventi in Oncologia–Studio Italiano Terapia Adiuvante Colon) study in which Dukes’ B2 or C colon cancers were randomized to receive six cycles of 5-fluorouracil plus folinic acid or observation. HRQL was measured at 0, 6, and 24 months after randomization. No difference in HRQL was identified based on treatment allocation. Information was, however, collected on less than 50% of patients at the 6- and 24-month time points, significantly limiting the strength of their conclusions. No comparisons are available yet that deal specifically with the issue of long-term impact of adjuvant therapy for rectal cancer on HRQL.1,2
The present study measured HRQL at a single point in time after the completion of therapy. It is not possible, therefore, to determine on an individual basis the effect of therapy on HRQL. Nor is it possible, based on this study, to determine inclusion or exclusion criteria for therapy based on an influence on HRQL. To address both of these issues, a large prospective multi-institutional study that serially evaluated HRQL before, during, and after therapy would be required. This current study does provide an important preliminary step in assessment of HRQL for CRC patients. It provides the insight that patients chosen for surgical or adjuvant therapy, or both, and surviving at least 6 months after completion of initial therapy, do not have vastly different long-term HRQL relative to patients undergoing either surgery for benign disease or, in the case of adjuvantly treated patients, surgery alone.
Received for publication April 19, 2000. Accepted for publication September 1, 2000.
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