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Long-term quality of life after radiotherapy for the treatment of anal cancer†
Article first published online: 29 DEC 2009
Copyright © 2010 American Cancer Society
Volume 116, Issue 4, pages 822–829, 15 February 2010
How to Cite
Das, P., Cantor, S. B., Parker, C. L., Zampieri, J. B., Baschnagel, A., Eng, C., Delclos, M. E., Krishnan, S., Janjan, N. A. and Crane, C. H. (2010), Long-term quality of life after radiotherapy for the treatment of anal cancer. Cancer, 116: 822–829. doi: 10.1002/cncr.24906
Presented in part at the 50th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, Boston, Massachusetts, September 21-25, 2008.
- Issue published online: 2 FEB 2010
- Article first published online: 29 DEC 2009
- Manuscript Accepted: 16 JUL 2009
- Manuscript Revised: 14 JUL 2009
- Manuscript Received: 29 MAY 2009
- quality of life;
- anal cancer;
- sexual dysfunction
Radiotherapy is the current standard of care for patients with localized squamous cell cancer of the anal canal. The goal of the current study was to evaluate long-term quality of life (QoL) in patients after this treatment.
Questionnaires were mailed to 80 patients treated with definitive radiotherapy, with or without concurrent chemotherapy, for anal cancer, with a minimum 2-year interval after the completion of radiotherapy. The questionnaire included the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), the Medical Outcomes Study (MOS) Sexual Problems Scale, and questions regarding demographic characteristics and comorbidities.
A total of 32 (40%) patients completed the questionnaire. There were no significant differences noted with regard to clinical and demographic characteristics between the survey responders and nonresponders. Among the 32 responders, the median dose of radiotherapy was 55 Grays (Gy), and 97% had received concurrent chemotherapy. The median interval between radiotherapy and survey participation was 5 years (range, 3-13 years). The median total FACT-C score was 108 (range, 47-128), of a maximum (best possible) score of 136. Patients who reported depression or anxiety and younger patients were found to have significantly lower total FACT-C scores. The median scores on the Physical, Social/Family, Emotional, Functional, and Colorectal subscales of the FACT-C were 20, 23, 21, 22, and 21, respectively, of maximum (best possible) scores of 28, 28, 24, 28, and 28, respectively. The median score on the MOS Sexual Problems Scale was 67 (range, 0-100), of a maximum (worst possible) score of 100.
Patients treated with radiotherapy for anal cancer reported acceptable overall QoL scores, but poor sexual function scores. Investigations are warranted into more modern radiation techniques that could potentially reduce late toxicity from radiotherapy. Cancer 2010. © 2010 American Cancer Society.
Radiotherapy with concurrent chemotherapy is the current standard of care for patients with localized squamous cell cancer of the anal canal.1-4 Chemoradiation serves as definitive treatment and allows sphincter preservation. The majority of patients treated with chemoradiation have excellent outcomes, with 5-year overall survival rates of approximately 75%.4 However, pelvic radiotherapy could potentially cause late toxicity, adversely affecting quality of life (QoL).5-12 To the best of our knowledge, only limited information is currently available regarding long-term QoL in patients treated with radiotherapy or chemoradiation for anal cancer.13-15
The goal of the current study was to evaluate long-term QoL in patients treated with definitive radiotherapy or chemoradiation for squamous cell cancer of the anal canal. Questionnaires were mailed to patients treated with radiotherapy or chemoradiation at a single institution, with a minimum 2 years of follow-up after the completion of treatment. The study was based on the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) instrument and the Medical Outcomes Study (MOS) Sexual Problems Scale.
MATERIALS AND METHODS
Eligibility criteria for this study included the following: patients treated with radiotherapy for nonmetastatic, squamous cell cancer of the anal canal between January 1993 and December 2003 at The University of Texas M. D. Anderson Cancer Center, and who were alive at the time of last follow–up. Exclusion criteria were age <18 years and inability to read English at the seventh grade level. Patients initially treated with radiotherapy who subsequently underwent salvage surgery were included. Patients were required to have a minimum 2-year interval from the time of the completion of radiotherapy to the time of the study.
Eligible patients were identified using hospital and radiation oncology departmental records, and The University of Texas M. D. Anderson Cancer Center Tumor Registry, which includes survival information from the Bureau of Vital Statistics. Mailing addresses of eligible subjects were verified by telephone calls, and subjects with verified addresses were mailed the study questionnaire. Subjects were asked to return the questionnaire by mail. If a response was not obtained, subjects were contacted up to 2 more times by mail or telephone to request participation in the study.
The study used the FACT-C instrument to assess QoL. The FACT-C has been shown to be both a reliable and valid measure of QoL in patients with colorectal cancer.16-19 Because to the best of our knowledge no instrument exists to specifically assess QoL in patients with anal cancer, and because anal and colorectal cancers have similar symptomatology and treatment–related side effects, we used the FACT-C instrument for the current study. The FACT-C is a self-administered questionnaire that consists of 34 items covering 4 domains of QoL: Physical, Social/Family, Emotional, and Functional, as well as a Colorectal subscale that is specific to the concerns of patients with colorectal cancer. Each item is rated on a scale from 0 to 4. The maximum score is 136, with higher scores indicating better QoL. In addition, the questionnaire included the MOS Sexual Problems Scale, a 4-item instrument with a maximum score of 100, with higher scores indicating worse sexual function.20-22 Furthermore, the questionnaire had 13 questions concerning demographic characteristics and comorbidities.
Chi-square tests were used to compare demographic and clinical characteristics between responders and nonresponders. Standard descriptive statistics, including the mean, median, range, and 95% confidence interval (95% CI), were calculated for the total FACT-C score; the Physical, Social/Family, Emotional, Functional, and Colorectal subscale scores; and the MOS Sexual Problems Scale. The Wilcoxon rank sum and Kruskal-Wallis tests were used to evaluate the effect of demographic, pathologic, and treatment factors on the QoL scores. A P value <.05 was considered to be statistically significant.
Patient and Treatment Characteristics
Eighty patients met the eligibility criteria for the current study and had verifiable mailing addresses; these patients were mailed the questionnaire. Of these 80 patients, 32 (40%) provided informed consent and completed the questionnaire. There was no significant difference noted with regard to the demographic, clinical, and treatment characteristics between the survey responders and nonresponders (Table 1). There was also no significant difference noted with regard to the rate of local failures or colostomies between the survey responders and nonresponders (Table 1). All colostomies were performed for recurrent or residual disease.
|No. of Patients (%)||No. of Patients (%)|
|Median age at diagnosis, y||51||54||.646|
|Male||6 (19%)||11 (23%)||.655|
|Female||26 (81%)||37 (77%)|
|White||29 (91%)||42 (88%)||.361|
|Black||2 (6%)||3 (6%)|
|Hispanic||0 (0%)||3 (6%)|
|Others||1 (3%)||0 (0%)|
|Negative||30 (94%)||48 (100%)||.157|
|Positive||2 (6%)||0 (0%)|
|T1||7 (22%)||8 (17%)||.307|
|T2||15 (47%)||15 (31%)|
|T3||6 (19%)||17 (35%)|
|T4||4 (12%)||8 (17%)|
|N0||23 (72%)||31 (65%)||.569|
|N1||5 (16%)||5 (10%)|
|N2||3 (9%)||7 (15%)|
|N3||1 (3%)||5 (10%)|
|Radiotherapy dose, Gy|
|<55||2 (6%)||4 (8%)||1.000|
|55||26 (81%)||39 (81%)|
|>55||4 (12%)||5 (10%)|
|AP/PA, then 3-field||30 (94%)||45 (94%)||1.000|
|Other||2 (6%)||3 (6%)|
|5-FU/cisplatin||23 (72%)||36 (75%)||.287|
|5-FU/mitomycin C||2 (6%)||7 (15%)|
|Capecitabine/cisplatin||6 (19%)||3 (6%)|
|5-FU||0 (0%)||1 (2%)|
|None||1 (3%)||1 (2%)|
|Locoregional failures||3 (9%)||6 (13%)||.734|
|Colostomy||3 (9%)||6 (13%)||.734|
Patients were staged based on physical examination, including digital rectal examination, proctoscopy, chest x-ray, and computed tomography (CT) scan. Among the 32 survey responders, the T classification was T1 in 7 (22%) patients, T2 in 15 (47%) patients, T3 in 6 (19%) patients, and T4 in 4 (12%) patients.23 The N classification was N0 in 23 (72%) patients, N1 in 5 (16%) patients, N2 in 3 (9%) patients, and N3 in 1 (3%) patient. All patients underwent CT simulation and were treated with 6- to 18-megavolt photons, along with electron fields when appropriate. Among the responders, 30 (94%) patients underwent radiotherapy initially with anterior and posterior fields, followed by a 3-field technique with posterior, right lateral, and left lateral fields; this technique has been previously described in detail.24 Among the responders, the median dose of radiotherapy was 55 Grays (Gy), with 30 (94%) patients receiving a dose ≥55 Gy and 31 (97%) patients receiving concurrent chemotherapy. The concurrent chemotherapy regimen was 5-fluorouracil (5-FU) and cisplatin in 23 (72%) patients, 2 of whom (6%) also received induction 5-FU and cisplatin. The concurrent chemotherapy regimen was 5-FU and mitomycin C in 2 (6%) patients, and capecitabine and cisplatin in 6 (19%) patients. The median interval between radiotherapy and survey participation was 5 years (range, 3-13 years).
Table 2 shows the mean, median, range, and 95% CIs for the total FACT-C score, the FACT-C subscales, and the MOS Sexual Problems Scale scores. On the FACT-C scale and subscales, higher scores indicated a better QoL. The median total FACT-C score was 108, of a maximum (best possible) score of 136. The median scores on the Physical, Social/Family, Emotional, Functional, and Colorectal subscales of the FACT-C were 20, 23, 21, 22, and 21, respectively, of maximum (best possible) scores of 28, 28, 24, 28, and 28, respectively. On the MOS Sexual Problems Scale, higher scores indicated worse QoL. The median score on the MOS Sexual Problems Scale was 67, of a maximum (worst possible) score of 100.
|Maximum Possible||Mean||Median||Range||95% CI|
|Total FACT-C scorea||136||104||108||47-128||60-124|
|MOS Sexual Problems Scaleb||100||51||67||0-100||0-100|
We evaluated the specific responses to all questions; items are presented if >20% patients reported a score in either of the 2 most unfavorable categories, and percentages were expressed in terms of the number of patients who answered that particular item. On the FACT-C questionnaire, 16 (55%) patients reported that they were “not at all” or “a little bit” satisfied with their sex lives, 7 (23%) patients reported having “not at all” or “a little bit” control of their bowels, 10 (31%) patients reported “quite a bit” or “very much” diarrhea, and 8 (25%) patients reported liking the appearance of their bodies “not at all” or “a little bit.”. On the MOS Sexual Problems Scale questionnaire, 17 (65%) patients reported that a lack of sexual interest was “somewhat” or “very much” of a problem, 17 (71%) patients reported that the inability to relax and enjoy sex was “somewhat” or “very much” of a problem, and 18 (72%) patients reported that difficulty in becoming sexually aroused was “somewhat” or “very much” of a problem. Among 6 men, 4 (67%) reported that difficulty having or maintaining an erection was “somewhat” or “very much” of a problem. Among 20 women who answered that question, 14 (70%) reported that difficulty in having an orgasm was “somewhat” or “very much” of a problem.
Factors Associated With QoL Scores
We evaluated the effect of various demographic, pathologic, and treatment factors on the QoL scores. The age at diagnosis was found to be significantly associated with the total FACT-C score (Table 3). The median total FACT-C score was 106 for patients aged <51 years at the time of treatment and 114 for those aged ≥51 years (P = .033). A history of depression or anxiety also was found to be significantly associated with the total FACT-C score. The median total FACT-C score was 92 for patients who reported depression or anxiety and 109 for those who did not report depression or anxiety (P = .006). Moreover, patients who reported depression or anxiety had significantly lower scores for the Physical subscale (median score of 17 vs 22; P = .005), Functional subscale (median score of 20 vs 25; P = .011), and Colorectal subscale (median score of 18 vs 22; P = .012). Patients who reported a history of other cancers were found to have a significantly lower score for the Physical subscale (median score of 17 vs 21; P = .044). No other factors were found to be significantly associated with the FACT-C total or subscale scores. No factors were found to be significantly associated with the MOS Sexual Problems Scale scores (Table 4). However, there was a trend toward a lower MOS Sexual Problems Scale score in those aged ≥51 years compared with those aged <51 years (median score of 29 vs 79; P = .107) and in those with a colostomy compared with those without (median score of 0 vs 67; P = .056). The time from treatment was not found to be significantly associated with any of the scores.
|Age at treatment, y|
|Time from treatment, y|
|Radiation dose, Gy|
|History of other cancers|
|History of gastrointestinal problems|
|History of depression/anxiety|
|Age at treatment, y|
|Time from treatment, y|
|Radiation dose, Gy|
|History of other cancers|
|History of gastrointestinal problems|
|History of depression/anxiety|
Although chemoradiation is the current standard of care for patients with squamous cell cancer of the anal canal, to the best of our knowledge only limited information is available regarding the long-term QoL of these patients. Because patients treated for anal cancer have high survival rates, long-term QoL is an important clinical issue. The results of the current study demonstrate that patients treated with radiotherapy or chemoradiation have acceptable overall QoL scores, but poor sexual functioning scores.
The mean total FACT-C score in this study was 104, of a maximum (best possible) score of 136. In comparison, a study of 903 patients with stage II and III colon cancer undergoing chemotherapy with 5-FU and leucovorin reported mean total FACT-C scores of 83 and 87, respectively, during chemotherapy and approximately 6 months after the completion of chemotherapy.18 A study of 201 patients who underwent surgery for colorectal cancer demonstrated a mean total FACT-C score of 80 at 6 weeks of follow-up.25 A study regarding 173 colorectal cancer survivors reported mean total FACT-C scores of 111, 112, and 115, respectively, 25 to 36 months, 37 to 60 months, and >60 months after diagnosis.26 Hence, the total FACT-C score reported in the current study compares favorably with that reported by colorectal cancer patients undergoing treatment, and appears similar to that reported by colorectal cancer survivors in long-term follow-up.
The mean MOS Sexual Problems Scale score in the current study was 51, of a maximum (worst possible) score of 100. In comparison, the mean Sexual Problems Scale score was reported to be 24 in patients with a major medical condition and 41 in patients with depression.20 A randomized study comparing total abdominal hysterectomy and supracervical hysterectomy in 135 women demonstrated mean Sexual Problems Scale scores of 20 in the total abdominal hysterectomy arm and 18 in the supracervical hysterectomy arm (scores were rescaled to be consistent with the current study).27 Thus, the Sexual Problems Scale scores in the current study compare unfavorably with those reported in studies of other high-risk groups. Moreover, a large percentage of patients reported unfavorable scores on each of the items on the Sexual Problems Scale, such as a lack of sexual interest, an inability to relax and enjoy sex, difficulty in becoming sexually aroused, difficulty having or maintaining an erection, and difficulty having an orgasm. It is interesting to note that these poor sexual function scores were reported by a population of relatively young patients, with a median age of 51 years at the time of cancer diagnosis. We hypothesize that the sexual dysfunction in these patients is a result of late radiation damage to the internal and external genitalia. Therefore, additional studies are warranted to further characterize the prevalence and etiology of sexual dysfunction after radiotherapy for anal cancer.
Although the total FACT-C scores and subscale scores appeared to be favorable in the current study, the responses to certain items give cause for concern. Specifically, approximately 31% of patients reported difficulty with diarrhea, 23% reported difficulty with bowel control, and 55% reported difficulty with their sex lives. The responses regarding sexual function are consistent with the findings from the Sexual Problems Scale. The long-term gastrointestinal symptoms could be a consequence of radiation damage to the small and large bowel, rectum, and anal canal.
Several dosimetric studies have recently demonstrated that intensity–modulated radiotherapy (IMRT) can reduce radiation dose to the genitalia in patients undergoing radiotherapy for anal cancer.28-31 In addition, IMRT can reduce radiation dose to the bowel, which may potentially reduce the rate of long-term diarrhea and difficulty with bowel control.29-31 However, the long-term gastrointestinal symptoms could partly be because of the effects of either the tumor or radiotherapy on the anal canal; IMRT will not be able to ameliorate anal canal related-toxicity, because the anal canal will be part of the target volume even with IMRT. Several clinical studies have recently evaluated IMRT for anal cancer; however, further follow-up will be required from these studies to determine whether IMRT can help reduce the risk of long-term sexual or gastrointestinal sequelae.30-32
In this study, younger patients were found to have significantly lower total FACT-C scores. Moreover, there was a trend toward worse Sexual Problems Scale scores in younger patients. Younger patients may have higher expectations regarding QoL and sexual functioning, which may have led to worse self-reported QoL scores in these patients.
The results of the current study indicate that more emphasis needs to be placed on identifying and addressing treatment-related symptoms after chemoradiation for anal cancer. Long-term follow-up of these patients is necessary to identify and treat the consequences of successful cancer therapy. Recent articles have reviewed the appropriate management of gastrointestinal and sexual dysfunction after pelvic radiotherapy.5, 33-35 Opiate agonists such as loperamide, bulking agents, and a low–fiber diet can help decrease gastrointestinal symptoms.5, 33 Phosphodiesterase inhibitors, such as sildenafil, can help improve sexual function in men, whereas topical estrogen, vaginal moisturizers, lubricants, and vaginal dilators can help improve sexual function in women.34, 35
Previous studies have evaluated QoL after radiotherapy for anal cancer. Tournier-Rangeard et al conducted a prospective study of QoL among 119 patients in a randomized controlled trial, using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire.36 This study indicated that QoL scores improved 2 months after chemoradiation, compared with before treatment; however, the study did not provide any information regarding long-term QoL. Vordermark et al reported a study on 22 colostomy-free anal cancer survivors, using the Gastrointestinal Quality of Life Index, which demonstrated a mean score of 114, compared with a mean score of 121 in healthy volunteers.14 However, their study did not evaluate nongastrointestinal aspects of QoL. Allal et al evaluated long-term QoL in 41 patients, using the EORTC QLQ-C30 and QLQ-CR38 questionnaires.13 Their study reported acceptable scores, except for a high symptom score for diarrhea and a low sexual functioning score, which are consistent with the findings of the current study. Jephcott et al compared QoL scores in 50 long-term anal cancer survivors and 50 matched volunteer controls, using the EORTC QLQ-C30 and QLQ-CR38 questionnaires.15 Anal cancer survivors were found to have significantly lower scores for overall QoL, as well as for the physical functioning and sexual functioning scales. Moreover, anal cancer survivors had significantly poorer scores for several symptom scales, including fatigue, nausea, diarrhea, gastrointestinal symptoms, defecation problems, and sexual problems. Although the findings in the current study are broadly consistent with those in previous studies, our study uses a different questionnaire (FACT-C) for assessing QoL, and also evaluates sexual function in greater detail, using the MOS Sexual Problems Scale questionnaire.
The current study has several limitations. The sample size was small; however, we believe that the study represents a significant contribution, given that squamous cell cancer of the anal canal is a relatively rare malignancy. The response rate was only 40% and it is possible that QoL scores could have been different between survey responders and nonresponders. However, there were no significant differences noted with regard to demographic, clinical, and treatment characteristics between survey responders and nonresponders. Information was not available regarding QoL, gastrointestinal function, and sexual function at baseline among these patients. Patients may have had some gastrointestinal or sexual dysfunction at baseline, and we were unable to account for these potential baseline deficits. Moreover, we evaluated QoL at a single timepoint, and therefore were unable to assess changes in scores for individual patients over time. For the overall group of patients, the time from treatment was not found to be significantly associated with any of the scores. We evaluated the relation between several factors and several scores, and these analyses were not corrected for multiple comparisons.
In conclusion, patients treated with radiotherapy or chemoradiation for squamous cell cancer of the anal canal reported acceptable overall long-term QoL scores, but poor sexual function scores. Moreover, the survey responses indicated that a significant percentage of patients had difficulty with diarrhea, bowel control, and different aspects of sexual function. Younger patients reported worse QoL scores. Clinicians need to identify and address treatment-related symptoms after radiotherapy for anal cancer. Modern techniques of radiotherapy, such as IMRT, could potentially reduce toxicity by reducing the radiation dose to the bowel and genitalia. However, studies with prolonged follow-up will be needed in patients treated with IMRT to determine whether IMRT mitigates against long-term gastrointestinal and sexual dysfunction.
CONFLICT OF INTEREST DISCLOSURES
Supported in part by Grant CA16672 from the National Cancer Institute, Department of Health and Human Services.
- 2Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997; 15: 2040-2049., , , et al.
- 3Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996; 14: 2527-2539., , , et al.
- 20Social functioning: sexual problems measures. In: StewartAL, WareJE, eds. Measuring Functioning and Well-Being: The Medical Outcomes Study Approach. Durham, NC: Duke University Press; 1992: 194-204..
- 23GreeneFL, PageDL, FlemingID, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag; 2002.