Abstract
Background/Aim: Opioids are a common treatment for cancer-related pain and information is limited on the rates of opioid use for cervical cancer patients. This study aimed to analyze outpatient opioid use and various predictors among patients with cervical cancer at a tertiary academic medical center. Patients and Methods: Data from patients with cervical cancer receiving treatment at a single institution, from August 2019 to July 2022, were retrospectively collected. Women with unrelated chronic opioid use or opioid use associated with acute inpatient stays were excluded. Charts were reviewed for patient demographics, disease characteristics, treatment characteristics, disease outcomes, and opioid prescriptions. The primary endpoint was duration of opioid use ≥6 months. Pearson’s chi-squared testing, Welch’s two-sample t-testing and Fisher’s exact testing were used to determine predictors of opioid use ≥6 months. Results: In total, 108 patients with cervical cancer (76.1%) of the 142 that received treatment were prescribed opioids. In women who were prescribed outpatient opioids, the median duration of opioid use was 69 days (interquartile range=5-359 days). In total, 40 (37.0%) had prescriptions for ≥180 days and 27 (25.0%) had prescriptions ≥365 days. On bivariate analysis, lower stage and receipt of surgery were associated with opioid use duration <6 months. Age, race, histology, substance/tobacco/alcohol use, depression/anxiety, and the receipt of brachytherapy/radiation were not associated with length of opioid prescriptions. Conclusion: This study demonstrated that 37% of patients with cervical cancer were using opioids for cancer-related pain longer than 6 months. Higher stage was associated with opioid use duration ≥6 months.
Cervical cancer is the third most common in incidence and cause of death among gynecologic cancers in the United States and the fourth most common cancer overall in females with a lifetime risk of 0.7% (1). The most common clinical manifestation is pain, often shifting from a treatment-related symptom to a chronic problem post-treatment in many patients. While early cervical cancer is often asymptomatic, with advanced disease the primary complaint is chronic pelvic or back pain (2). Common treatment regimens for cervical cancer include surgery, radiation, and chemotherapy (2). These treatment modalities have different chronic pain syndromes with surgery potentially causing lasting lymphedema, neuralgia, and chronic back/pelvic pain, radiation potentially causing vaginal stenosis, pelvic insufficiency fractures, and myelopathy, and chemotherapy potentially causing osteoporosis/osteonecrosis and chemotherapy-induced peripheral neuropathy (3).
Reports suggest that cervical cancer patients at the time of recurrence/presentation have higher rates of opioid use compared to other cancer types (4-6). However, there is minimal data on opioid prescription patterns after initial treatment (surgery, chemotherapy, and radiation) has been completed. As a result, it is critical to examine and understand the use of opioids in this patient population. This study aimed to analyze outpatient opioid use and various predictors among patients with cervical cancer at a tertiary academic medical center.
Patients and Methods
Data from patients with cervical cancer receiving curative treatment at a single institution, from August 2019 to July 2022, were retrospectively collected. All patients received multidisciplinary evaluation prior to treatment from gynecologic oncology, radiation oncology, pathology, and genetics specialists. A waiver of informed consent was provided by our institutional review board due to the minimal risk posed to study participants.
Charts were reviewed for patient demographics, disease characteristics, treatment characteristics, disease outcomes, and opioid prescriptions. Clinical and demographic data was abstracted using institutional electronic medical records. The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging was used to classify patients’ stages. Women with unrelated chronic opioid use or opioids use associated with acute inpatient stays were excluded. “Outpatient opioid use” was defined as any outpatient opioid prescription, including postprocedural medications. Duration of opioid use was determined by counting days and months of written prescriptions for any opioid in the electronic medical record. The primary endpoint was duration of opioid use ≥180 days. Pearson’s chi-squared testing, Welch’s two-sample t-testing and Fisher’s exact testing were used to determine predictors of opioid use ≥180 days.
Results
From August 2019 to July 2022, 108 patients, constituting 76.1% of the 142 individuals who received treatment for cervical cancer, were prescribed opioids. The mean age at diagnosis was 47.3 years. Patient and treatment characteristics of patients prescribed opioids are included in Table I. The majority of patients receiving opioids were white (73.1%), had Stage I disease (56.5%), and had squamous cell carcinoma histology (69.4%). Surgery was the most prevalent treatment modality (48.1%). The majority reported a tobacco use history (59.3%), but substance use (6.5%) and alcohol use (1.9%) were less common. Additionally, depression and anxiety were present in 25% and 23.1% of patients.
Demographic and medical characteristics of patients with cervical cancer who were prescribed opioids at some point in their treatment.
Opioid prescription types are presented in Table II and Figure 1. In women who were prescribed outpatient opioids, the median duration of opioid use was 69 days (interquartile range 5-359 days). In total, 40 (37.0%) had prescriptions for ≥180 days and 27 (25.0%) had prescriptions ≥365 days. The single most commonly prescribed opioid was oxycodone (50.1%). Multiple opioid prescriptions were used in one-third of patients (33.3%). In terms of predictors of opioid use, higher stage was statistically associated with opioid use ≥180 days (p<0.0001). For example, for patients prescribed opiates <180 days, 75% were stage I while for those using opiates ≥180 days, the highest percentage (42.5%) of patients were stage III. Since early-stage patients are the only appropriate candidates for surgical resection, patients undergoing surgery were statistically significantly associated with opioid prescriptions <180 days (p=0.0020). Age, race, histology, substance/tobacco/alcohol use, depression/anxiety, and the receipt of brachytherapy/radiation were not associated with length of opioid prescriptions.
Opioid prescription characteristics.
Types of opioids prescribed.
Discussion
This study sought to explore outpatient opioid use of cervical cancer patients along with various predictors, and the findings demonstrated that for all cervical cancer patients treated at our institution, 76.1% were given at least one prescription for opioids. Of the 108 patients prescribed opioids, 40 (37.0%) had prescriptions for 180 days (~6 months) or more and 27 (25.0%) had prescriptions lasting longer than 365 days (1 year).
This rate of opioid usage among cervical cancer patients is greater than that of opioid use for chronic pain in cancer survivors in general (7). However, our reported incidence of long term (>6 month) opioid use is similar to results from other series. In a series of 106 patients with cervical cancer treated at two urban medical centers, Arya et al. reported 35.2% and 22% of patients had an opioid prescription lasting longer than six and 12 months, respectively (8). In a study specific to patients with cervical cancer receiving radiation, Ward et al. reported that 25% of the 96 patients included in the study were still using opioids 6 months after radiation (9).
In terms of predictors of long-term opioid use, we found that higher stage was associated with use ≥180 days. This makes sense for multiple reasons. Patients with higher stage disease have larger, more advanced tumors that are invading more normal tissues, contributing to pain symptoms. In addition, these patients often require more treatment modalities and more invasive treatment techniques (interstitial brachytherapy) that contribute to morbidity and pain. Finally, these patients are at highest risk for recurrence; pelvic recurrences can cause debilitating pain. We also found that surgery as primary treatment was associated with short term opioid use (<180 days). This correlates with our finding of stage as a predictor for opioid use duration. Surgical treatment of cervical cancer is generally reserved for early stage patients with small volume disease and lower risks of recurrence (2). As a result, these patients would be at lower risk of long-term opioid use. Increased emphasis on adherence to established cervical cancer screening guidelines would allow for earlier detection of disease and less morbid treatment options.
Other previously reported risks factors for persistent opioid use include mental health disorders (such as depression and anxiety), tobacco use, alcohol use, and/or other substance use (10, 11). While these disorders were present in our cohort of patients, they were not significantly associated with opioid use ≥180 days amongst our patients. Several reasons may be responsible for this, including inaccuracies in reporting from patients and/or healthcare providers and bias against using opioids in patients with these risk factors. Previous studies have noted that alcohol and substance abuse disorders are typically under-reported and under-documented in patients (12, 13). This is important as prescribing opioids in these patients can put them at risk for increased side effects and complications. In addition, recent data suggests that patients with cervical cancer are more likely to be screened as a moderate to high risk for opioid misuse compared to women with other gynecologic malignancies (14). Therefore, careful history taking is necessary when prescribing opioids.
This is not to say that opioids should not be used as patients with cervical cancer have been found to require more opioids than those with other gynecologic malignancies (6). The American Society of Clinical Oncology (ASCO) and the Society of Gynecologic Oncology (SGO) advocate that steps should be taken to decrease opioid misuse, but that these should not interfere with access to opioids for cancer-related pain (15). Brief screening tools have been developed to predict individuals that may develop aberrant behaviors when prescribed opioids for chronic pain with great specificity and sensitivity, such as the self-administered Opioid Risk Tool (10). Chronic pain management guidelines recommend a multidisciplinary approach that uses multiple modalities that provide comfort and function for daily life and includes pharmacologic treatment, cognitive-behavioral methods, physical medicine and rehabilitation, integrative medicine, and interventional approaches. Regarding pharmacologic approaches, there is weak evidence that long-term continuation of opioids provides clinically significant pain relief in chronic non-cancer pain despite increased usage (7). Studies have found that opioid abuse and dependence are diagnosed in a small minority of patients receiving chronic opioid therapy, but this may be underestimated (11).
The strengths of this study include the relatively large sample size and consistency of how the data of prescriptions provided to patients has been collected within the same electronic medical record modality, and it has been collected over a time span of 3 years that has consisted of similar treatment approaches. The limitations of this study are the retrospective nature of the data collection, the cohort coming from a single tertiary academic center, and that the data included only prescriptions given and not the actual usage of the prescriptions.
Conclusion
In this single institution review of cervical cancer patients, we found a significant percentage of patients prescribed opioids received long term prescriptions and that higher stage disease was associated with persistent opioid use. Providers should strive for decreased opioid use after treatment among this cancer patient population while still providing adequate pain control. This includes future exploration into non-opiate therapy for cancer-related chronic pain, earlier engagement of palliative care specialists and increased awareness of provider opioid stewardship.
Acknowledgements
The study was supported by the Biostatistics Shared Resource of University of Arkansas for Medical Sciences Winthrop P. Rockefeller Cancer Institute.
Footnotes
Authors’ Contributions
NM: Methodology, Investigation, Visualization. AK: Methodology, Investigation, Data Curation. HJS: Formal Analysis, Data Curation. HRW: Conceptualization, Writing – Review & Editing, Supervision. SS: Conceptualization, Writing – Review & Editing, Supervision. GDL: Conceptualization, Methodology, Investigation, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization, Supervision, Project administration.
Conflicts of Interest
The Authors have no conflicts of interest to disclose in relation to this study.
- Received November 9, 2023.
- Revision received November 30, 2023.
- Accepted December 1, 2023.
- Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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