Quality of Life and Sexual Functioning in Cervical Cancer Survivors

Michael Frumovitz, The University of Texas M.D. Anderson Cancer Center, Journal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7428-7436

Additionally, over half of women are diagnosed with stage I disease when the tumor is clinically limited to the cervix. Primary treatment with surgery or irradiation alone cures 85% to 90% of patients with stage I cervical cancer. Despite similar effectiveness, however, each treatment modality involves distinct clinical acute and late complications.

The surgical approach to early-stage cervical cancer consists of radical hysterectomy and bilateral lymph node dissection, with or without accompanying oophorectomy or ovarian transposition. Blood loss remains the most significant intraoperative complication with transfusion rates reaching as high as 80%. Postoperatively, patients may experience febrile morbidity, deep vein thrombosis, pulmonary embolism, wound dehiscence, postoperative bladder dysfunction, and fistula formation. In addition, a small but real risk of operative mortality exists with the surgery. Long-term complications can include bladder hypotonia requiring chronic self-catheterization, ureteral strictures, and chronic leg lymphedema.

Radiotherapy, typically consisting of external beam radiation followed by intracavitary radiation, has its own spectrum of complications. Potential complications from intracavitary radiation include uterine perforation and febrile morbidity. Although deep vein thrombosis, pulmonary embolism, and even death are potential risks with intracavitary radiotherapy, they are exceedingly rare.Patients who receive radiation may also experience early small bowel complications (obstruction); early or late large bowel complications (bleeding, stricture, fistulae, perforation); late urinary complications (hematuria, ureteral stenosis, vesicovaginal fistula); and vaginal atrophy, shortening, or agglutination.The latter can make sexual intercourse difficult or even impossible. Although radical hysterectomy and radiotherapy are associated with comparable rates of complications, the quality, chronicity, and severity of these complications are difficult to compare.

Whether the patient undergoes primary surgery or radiotherapy depends on a variety of factors, including tumor characteristics, comorbid medical conditions, and patient and provider preference. Patients who are likely to require adjuvant radiotherapy following radical hysterectomy often undergo primary radiotherapy in an effort to minimize the morbidity and mortality associated with combined treatment modalities. Factors that might dispose physicians to recommend primary radiotherapy include large tumor volume, lymphatic involvement, aggressive tumor histology, and depth of invasion.  In reality, however, many women with stage IB1 tumors are equally good candidates for either surgical management or radiotherapy. In these situations, the clinical decision is often based on patient or provider preference.

The objective of this study was to perform a comparison of the quality of life (QOL) of women with early-stage cervical cancer that could be treated equally effectively with either surgery or radiotherapy. Standardized questionnaires were used to measure outcomes, and a group of healthy age- and race-matched women with no personal history of cancer was included in the comparison to determine if any differences in QOL exist between women with cervical cancer and women without a history of cancer. The ultimate aim of the study was to provide patients and providers with additional empirical information to help guide their treatment choice.

PURPOSE: To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy.

METHODS: Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer.

RESULTS: One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures.

CONCLUSION: Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.

To our knowledge, this is the first study to measure not just sexual functioning, but also emotional adjustment, relationship satisfaction, and menopause symptoms after surgery or radiation treatment alone in patients with cervical cancer, as well as in a group of women without a cancer diagnoses. The consistently increased morbidity across all measures in irradiated women is striking, and persists for sexual functioning even after controlling for potentially confounding factors such as educational level and tumor stage.

Although the desire for sexual intimacy was equal among all groups, irradiated patients had significantly more sexual dysfunction than women in the other two groups. These findings agree with the previous prospective studies comparing women treated with surgery alone or radiation therapy alone. Jensen found women treated with radiation therapy had more severe sexual dysfunction at 2-year follow-up, with 85% of women reporting no interest in sex, 55% having dyspareunia, and 50% having vaginal shortening. These problems were significant compared with the women's own premorbid sexual function and when compared with age-matched controls.

The timing of follow-up is very important in these patients since sexual and other morbidities improve during the first year after radical hysterectomy, whereas the chronic fibrotic changes in pelvic tissue after radiotherapy create persistent, or even worsening vaginal atrophy at least up to 2 years post-treatment.  It is not surprising then to find continued adverse sexual functioning in these women who were irradiated 5 or more years ago. For these reasons, we strongly recommend either the use of a vaginal dilator or the engagement in sexual intercourse frequently after completion of radiotherapy for cervical cancer in an effort to maintain the length, width, and elasticity of the vaginal canal. Future research might follow these patients longitudinally with pretreatment baseline sexual functioning data.

Patients who had undergone radical hysterectomy did not differ in sexual functioning from age- and race-matched peers. This finding is in accord with a previous study that of early-stage cervical cancer patients treated with radical surgery. In their second study, Jensen  also found no significant difference in overall sexual function between women posthysterectomy and healthy controls. In contrast to our results, women in the radical hysterectomy group were almost three times more likely than controls to have difficulty with vaginal lubrication. However, nearly one third of these patients had undergone concurrent bilateral salpingo-oophorectomy, and no attempt was made to control for menopausal status between treatment and control arms.

Bergmark have published the largest series on sexual functioning in cervical cancer survivors. In their study, they surveyed 256 Swedish cervical cancer survivors (4 to 6 years after treatment) and compared them to controls matched for age and geographic region. Their cancer arm was women with local (stage IB) or locoregional (stage IIA) disease who had been treated with a variety of modalities including radical hysterectomy alone, radiation alone, and combination radiotherapy and surgery. When comparing the entire cancer cohort to controls, they found no difference in sexual desire or orgasm between the groups but found an increase age-adjusted risk ratio for the cancer patients in regards to vaginal lubrication, genital swelling/arousal, perceived vaginal length and elasticity, dyspareunia, and coital bleeding. When they performed a subanalysis grouped by treatment, they found no difference in lubrication, genital swelling/arousal, vaginal elasticity or length, or libido when comparing surgery patients with irradiated patients to patients who had received multiple modality therapy. They did, however, find that the surgery only patients reported statistically significant differences in vaginal lubrication, vaginal length, and vaginal elasticity when compared with controls.

These findings contrast with the current study, which showed significant differences on all subscales of the FSFI (except arousal) for irradiated patients and no differences between surgery only patients and controls. There are multiple possibilities for these discrepancies. First, Bergmark et al utilized a survey created by them and not one that had been subjected to tests of reliability and validity. Next, they did not report or account for any ovarian procedures performed during radical hysterectomy. Many of those women were made menopausal with either surgery or radiation with little or no accounting. In addition, their patient population, which included women as old as 80 years and patients who had multiple modality treatment differs greatly from ours. Finally, although they reported hormonal status for both patients and controls, they made no attempt to control for it, or any other factor, in a regression analysis, which likely introduced multiple confounders into the study.

Irradiated patients had statistically significant worse sexual functioning, physical health, and emotional distress after the first step, before the addition of the menopause symptom score. After accounting for the menopause score, only sexual functioning remained significantly worse for those women who been irradiated. We believe that the irradiated patients probably had worse physical health and possibly more psychologic distress, but the menopausal symptom overall scores masked the treatment effect in the statistical analysis because of the high one-to-one correlation between adverse menopausal symptoms and the radiotherapy patients. Therefore, the menopausal symptom score likely overshadowed the other relationships observed before its addition into the multivariate model. When we compared patients rendered menopausal by surgical oophorectomy with those made climacteric by radiotherapy, menopausal symptom scores were significantly worse for the irradiated women. This was probably due to the fact that many of the symptoms surveyed by the instrument can be attributed to either menopause or radiotherapy. This may explain why the two groups with loss of ovarian function had similar rates of hot flashes (symptoms unique to menopause) but differed significantly in their assessment of vaginal dryness and urinary symptoms (likely a result of radiotherapy). In addition to causing ovarian failure, radiotherapy directly affects the vaginal mucosa by decreasing blood flow to the vaginal walls and causing pelvic fibrosis. For these reasons, even topical estrogen cream is less well absorbed and less effective in reversing menopausal changes in the vagina after radiotherapy.