We identified 531 potentially eligible participants using the fellow surgical case logs and ICD-9 codes. Among the 531 mailed letters, we had a 43% response rate. Sixty-seven potentially eligible participants were not interested in participating in our study, and 213 potentially eligible participants did not respond to either the letter or the mailed survey. There were 19 letters returned by the post office, labeled as undeliverable, and an additional seven people had died. A total of 225 participants returned the surveys, and 12 were subsequently identified as not meeting inclusion criteria (i.e., 10 diagnosed with cancer before 2006 and two misclassified (diagnosed with other gynecologic cancers)). The remaining 213 eligible participants replied to our survey and contributed data to the study analyses.
Among the 213 participants, 77 (36%) reported five or more symptoms on the GCLQ and were classified as having LLL. There existed no significant difference in demographic and clinical characteristics between women classified as having LLL versus not having LLL.
Among the 213 study participants, 40%, 13%, 13%, and 35% reported participating in <3.0, 3.0–8.9, 9.0–17.9, and ≥18.0 MET·h·wk−1 of PA, respectively (Table 3). The odds of LLL decreased as MET-hours per week of PA increased (Ptrend = 0.003). Compared with participants who reported <3 MET·h·wk−1 of PA, participants who reported ≥18.0 MET·h·wk−1 of PA had an OR of 0.32 (95% CI, 0.15–0.69). The most common PA reported were walking (42%), aerobic gym-based activities including the recumbent bicycle and elliptical machine (11%), and swimming (8%).
Among the 213 study participants, 36%, 26%, and 38% reported walking <4.0, 4.0–11.9, and ≥12 blocks per day, respectively (Table 3). The odds of LLL decreased as the blocks per day of walking increased (Ptrend < 0.0001). Compared with participants who reported <4.0 blocks per day of walking, participants who reported ≥12 blocks per day of walking had a multivariable-adjusted OR of 0.19 (95% CI, 0.09–0.43).
Among the 213 study participants, 26%, 22%, and 52% reported a BMI of <25.0, 25.0–29.9, and ≥30.0 kg·m−2, respectively (Table 3). The odds of LLL did not change as BMI increased (Ptrend = 0.85).
The major findings of this study are that 36% of uterine cancer survivors in our sample have LLL on the basis of symptom self-report, and uterine cancer survivors who participate in more PA and walking are less likely to report symptoms sufficient for a diagnosis of LLL. These findings, particularly PA participation, were more pronounced among women with BMI <30 kg·m−2. BMI was not independently associated with LLL. Our data now provide evidence linking PA, walking, and LLL. Among uterine cancer survivors who engage in the highest level of PA or walking, there were 68% and 81% reduced odds of reporting LLL compared with uterine cancer survivors who engage in the lowest levels of PA or walking, respectively.
Although these findings are promising, they should be interpreted as preliminary. The major limitation of this study is the cross-sectional design, in which it is impossible to determine the direction of any causal association. It is plausible that uterine cancer survivors who engage in more PA or walking subsequently experience fewer LLL-related symptoms. Conversely, it is plausible that uterine cancer survivors with more severe LLL symptoms may be physically or psychologically unable to engage in PA or walking. BMI in our study was self-reported, which may be subject to bias. However, BMI is highly correlated with objective measures of height and weight and is appropriate for epidemiologic studies (29). PA in our study was self-reported. Although self-reported PA is valid and correlated with objective measures of PA (47), 47% of participants in our study reported meeting PA guidelines (i.e., ≥9.0 MET·h·wk−1), whereas only approximately 10% of US adults meet such guidelines (48). Therefore, it is plausible that participants in our study may have over-reported their PA, consistent with the hypothesis that uterine cancer survivors are less physically active and have higher BMI. Another limitation of our study was the omission of question 20 in the “general swelling” domain of the GCLQ survey. The current gold standard method to diagnose LLL is the circumferential measures of the lower limbs and a clinical examination. However, this method has not been adopted for use in routine clinical care (8). Our method to assess LLL relied on symptoms determined using a self-report questionnaire that was validated against circumferential measures of the lower limbs and had excellent psychometric characteristics (10).
The optimal exercise modality to reduce LLL symptom burden is unknown. This is a result of a limited understanding of the physiologic complexities of LLL. People with PAD use treadmill walking as a rehabilitative modality to improve leg claudication symptoms (17). Resistance training has also been recommended as a useful adjunct to treadmill walking for people with PAD (31). Among 156 people with PAD who were randomized to 24 wk of aerobic treadmill walking, lower extremity resistance training, or control, people in the aerobic treadmill walking group had significantly improved 6-min walking distance times and improved time to onset of leg symptoms compared with those in the control group (31). The weightlifting group had improved quality of life and stair climbing ability compared with the control group (31). The three-arm design such as that described previously may be the most efficient approach to test the safety and efficacy of various exercise modalities among uterine cancer survivors with LLL.
Recent evidence has emerged that weightlifting exercise is a safe and efficacious modality for upper extremity lymphedema among breast cancer survivors (36,39). Among breast cancer survivors with upper extremity lymphedema, weightlifting resulted in a 50% risk reduction of lymphedema exacerbations requiring medical treatment and a significant reduction in the severity of self-reported lymphedema symptoms over 1 yr (36). Despite physiologic differences between upper extremity lymphedema and LLL, a hypothesis would be to examine the use of weightlifting among cancer survivors with LLL. A small pilot study of weightlifting has been conducted among 10 cancer survivors with LLL (24). After 5 months of weightlifting, participants had improvements in muscular strength and physical functioning (P < 0.05) compared with baseline values. There were no significant changes in objective LLL leg volume when measured using perometry. Two of the 10 participants developed cellulitis, a bacterial infection requiring broad-spectrum antibiotics during the study. Therefore, the safety and efficacy of weightlifting among cancer survivors with LLL remains to be elucidated (24).
Daily voluntary walking has been demonstrated to correlate with the distance women can walk without difficulty (6). Furthermore, a program that increases voluntary walking may have implications for disability, mortality, and health care costs (18). Compared with those who could walk 0.25 mile without difficulty, those who had difficulty or were unable to walk 0.25 mile were at 1.57- or 2.73-fold higher risk for mortality among 5895 community-dwelling older adults, respectively. A dose–response relation between ability to walk 0.25 mile and medical care costs and hospitalizations has been observed: as ability to walk 0.25 mile decreases, medical care costs and hospitalizations may increase proportionally (18). Therefore, future intervention studies designed to improve functional mobility among uterine cancer survivors with LLL may provide a multitude of benefits, including reduced disability, mortality, and health care costs. To this end, randomized controlled trials designed to reduce disability among uterine cancer survivors with LLL should consider these outcomes as being important on patient and policy levels (4).
As noted in the introduction, if LLL precludes women participating in the recommended levels of PA (i.e., if reverse causality exists), then our findings have clinical implications. For example, it is important for clinicians to know that the ACSM guidelines for exercise among cancer survivors (38) may need to be tailored to allow women with LLL to engage in PA that is safe, feasible, and efficacious to promote their physical and mental health. Future cohort studies that measure PA after diagnosis and follow participants longitudinally until incident LLL diagnosis would help to delineate the temporal relation of PA with LLL. In the absence of reverse causality, PA may be an intervention to prevent LLL among those at risk of developing LLL and to reduce symptom burden among those with LLL. The potential utility of PA across the LLL spectrum—from prevention to treatment—is consistent with other forms of lymphedema such as upper extremity lymphedema among breast cancer survivors. For example, weightlifting reduces the risk of incident upper extremity lymphedema by 36% among those at risk of developing upper extremity lymphedema (37) and reduces the need for complete decongestive treatment by 53% among those with upper extremity lymphedema (36). Our hypothesis is that PA would have similar effects on LLL like that of upper extremity lymphedema. The remaining questions to be answered include 1) the temporal sequence of PA and incident LLL, 2) the efficacy and safety of PA to prevent and/or treat LLL, and 3) the type of PA modality (i.e., aerobic, resistance, and neuromuscular) that should be prescribed to maximize LLL outcomes and promote the health and longevity of uterine cancer survivors.
Among uterine cancer survivors, approximately 36% have LLL, determined using a validated symptom self-report (10). Participation in higher levels of PA or walking was associated with reduced proportions of LLL in dose–response fashion, such that the group who engaged in the highest levels of PA or walking reported the smallest proportion of LLL cases. These findings should be interpreted as preliminary and should be subject to investigation in future studies.
This work was completed without funding.
The senior author, K. H. Schmitz, has received funding from the National Institutes of Health unrelated to this work.
All other authors declare there are no conflicts of interest.
The results of this study do not constitute endorsement by ACSM.
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