Ann Surg Oncol DOI 10.1245/s10434-014-3562-4
ORIGINAL ARTICLE – GYNECOLOGIC ONCOLOGY
Comparative Patient-Centered Outcomes (Health State and Adverse Sexual Symptoms) Between Adjuvant Brachytherapy Versus No Adjuvant Brachytherapy in Early Stage Endometrial Cancer Shari Damast, MD1, Kaled Alektiar, MD2, Anne Eaton, MS2, Naamit Kurshan Gerber, MD2, Shari Goldfarb, MD2, Sujata Patil, PhD2, Rachel Jia, MS2, Mario Leitao, MD2, Jeanne Carter, PhD2, and Ethan Basch, MD, MSc3 1
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT; 2Memorial Sloan-Kettering Cancer Center, New York, NY; 3University of North Carolina, Chapel Hill, NC
ABSTRACT Purpose. To determine a relationship between sexual functioning and health state among survivors of stage I endometrial cancer, and to examine whether adjuvant intravaginal radiotherapy (IVRT) affects these measures compared to hysterectomy alone. Methods. Two hundred five survivors ([1 year from surgery) completed questionnaires containing the EuroQol (EQ5D) and the Female Sexual Function Index (FSFI). A total of 136 (66.3 %) underwent surgery alone, and 69 (33.7 %) received IVRT. Pearson correlation was used to correlate FSFI and EQ5D–Health State scores. Multivariable regression was performed to measure the impact of IVRT on sexual functioning and health state. Results. A majority of patients (80 %) met criteria for sexual dysfunction by FSFI \ 26.5. A significant correlation was detected between FSFI and EQ5D scores (Pearson correlation = 0.21, p = 0.003). Compared to the IVRT group, the surgery group was younger (p = 0.001) and trended toward more frequent use of minimally invasive surgery versus laparotomy (p = 0.08). Otherwise, the two groups were well balanced with respect to demographics, comorbidities, and baseline sexual activity. Controlling for age and surgery type, IVRT was not associated with poorer health state or sexual function. Receipt of laparotomy was associated with both poorer health state and sexual function (p = 0.0156 and p = 0.0247, respectively).
Ó Society of Surgical Oncology 2014 First Received: 1 May 2013 S. Damast, MD e-mail:
[email protected]
Conclusions. Sexual functioning was generally poor among endometrial cancer survivors; however, those with improved FSFI scores tended to have superior health states. IVRT was not a significant risk factor; however, receipt of laparotomy appeared to be associated with poorer sexual functioning and health state.
Endometrial cancer (EC) is the most common gynecologic malignancy in the United States.1 It presents frequently in early stage and is curable in a majority of patients with simple hysterectomy with or without radiotherapy (RT).1 Adjuvant RT offers an additional local control benefit when adverse features such as older age, deep myometrial invasion, grade 2 or 3 disease, or lymphovascular invasion, are present.2,3 Intravaginal radiotherapy (IVRT) is a common form of adjuvant RT as a result of its noninferiority to pelvic RT and more favorable toxicity profile, as demonstrated by the Postoperative Radiotherapy for Endometrial Cancer (PORTEC-2) group.4–6 When no adverse risk factors are present, the benefit of adjuvant IVRT in early stage EC may be less robust, and observation may be considered as an alternative.7,8 In this setting, adjuvant IVRT is tailored to pathologic characteristics, comorbid conditions, physician and patient beliefs and preferences, as well as an understanding of treatment toxicities and impact on quality of life (QOL). The primary toxicity from IVRT concerns biologic changes of the vaginal mucosa, which are usually grade 1 or 2 toxicities.7 These may manifest as vaginal discharge, bleeding, erythema, ulceration, and agglutination.9 Longterm effects may include fibrosis, atrophy, dryness, and
S. Damast et al.
vascular damage.10 Vaginal shortening and stenosis are described as the most common late anatomic changes from IVRT.11,12 Whether receipt of IVRT has a negative impact on patients’ sexual functioning and QOL compared to observation has not been conclusively addressed. Several recent studies have focused on this question, however, with limited patient numbers, ranging between 13 and 20 IVRT patients.13–15 To further understand the importance of sexual functioning in EC survivorship, a study was designed to determine whether sexual functioning correlated with health state among several hundred stage I EC survivors, and whether receipt of IVRT was a negative predictor of outcome.
PATIENTS AND METHODS
Assessed for eligibility (N = 553) Excluded (n = 63) -not meeting inclusion criteria (n = 27) -recurrent disease (n = 28) -language (n = 8) Patients initially eligible for study (n = 490) Excluded (n = 39) -Declined participation (n = 39) Remaining patients eligible for study (n = 451)
Surgery alone (n = 264)
Surgery + IVRT (n = 187)
Survey returned (n = 173) 66% response rate
Surveys returned (n = 137) 73% response rate
Study Population Memorial Sloan-Kettering Cancer Center (MSKCC) institutional databases were queried for patients with stage I EC treated from 2003 to 2009 with hysterectomy with or without IVRT. Patients who had received chemotherapy, hormone therapy, or external beam RT were excluded. Patients were also excluded if they had a separate cancer diagnosis apart from EC, were deceased, or lacked recent follow-up (defined as no clinic visit in the prior 12 months), or if they had requested to be on the institutional do-not-contact list. The initial search retrieved 243 patients treated with adjuvant IVRT and 310 patients treated with surgery alone. After record review, subsequent exclusions were made for the following reasons: (1) not meeting prespecified inclusion criteria (6 IVRT; 21 surgery alone); (2) evidence of disease recurrence (21 IVRT; 7 surgery alone); (3) nonEnglish-language speaking (7 IVRT; 1 surgery alone). The resulting 490 patients (209 IVRT; 281 surgery alone) received a letter detailing the aims of the study. The letter was signed by their surgeon or radiation oncologist and included a provisional statement allowing the subject to refuse participation. Participation was voluntary, and no compensation was offered. An additional 39 patients (22 IVRT; 17 surgery alone) indicated refusal to participate and were therefore excluded from the study. The resulting 451 patients (187 IVRT; 264 surgery alone) received the study questionnaire. These numbers are outlined in Fig. 1. All aspects of the study design, including the database search, survey distribution, data collection, and analysis, were approved by the MSKCC institutional review board before commencing the study.
Excluded (n = 37) -time from hysterectomy (n = 5) -FSFI score (n = 32)
Analyzed (n = 136)
Excluded (n = 68) -time from hysterectomy (n = 45) -FSFI score (n = 23)
Analyzed (n = 69)
FIG. 1 Flow diagram of patient population
Treatment All patients received treatment at MSKCC. Surgery was a total hysterectomy. Either laparotomy or minimally invasive surgery was permitted. Complete surgical lymph node staging was performed when feasible. Patients with no myometrial invasion and grade 1 or 2 disease received hysterectomy alone. Others received adjuvant IVRT with a Varian Gamma-Med after loading high-dose-rate Ir-192 source, with a prescription dose of 1,800–2,100 cGy to the upper half or two-thirds of the vagina, prescribed to a depth of 0.5 cm from the surface. Instruments The questionnaire was deidentified. Items included age group (\50, 50–59, 60–69, 70–79, 80? years), ethnicity, marital status, education level, medical comorbid conditions, time interval from hysterectomy, surgery type, performance status, and use of interventions for sexual functioning. The questionnaire can be found in Appendix. The EuroQoL EQ5D was incorporated to assess health state. It is a validated general measure of health-related QOL, which consists of five descriptive questions concerning domains of mobility, self-care, usual activities,
Comparative Patient-Centered Outcomes in EC TABLE 1 Characteristics of patients and comparison of those who received IVRT with those who did not Characteristic
No IVRT (n = 136), no. (%)
IVRT (n = 69), no. (%)
\50
16 (11.8)
4 (5.8)
50–59
50 (36.8
9 (13.0
60–69
51 (37.5)
31 (44.9)
70–79
17 (12.5)
16 (23.2)
80?
2 (1.5)
9 (13.0)
Time from hysterectomy (years) 43 (31.6)
15 (21.7)
2–3
27 (19.9)
9 (13.0)
3–4 4–5
13 (9.6) 25 (18.4)
14 (20.3) 11 (15.9)
[5
28 (20.6)
20 (29.0)
Race/ethnicity 112 (82.4)
56 (82.4)
Black/African American
10 (7.4)
4 (5.9)
Asian
8 (5.9)
2 (2.9)
Hispanic
4 (2.9)
4 (5.9)
Other
2 (1.5)
3 (4.3)
Diabetes 28 (20.6)
10 (14.5)
55 (40.4)
25 (36.2)
25 (18.4)
12 (17.4)
82 (60.3)
Divorced
14 (10.3)
5 (7.2)
Single
22 (16.2)
13 (18.8)
14 (10.3)
7 (10.1)
4 (2.9)
4 (5.8)
56 (41.2)
30 (43.5)
Education level
0.940
College degree
43 (31.6)
20 (29.0)
High school degree
36 (26.5)
18 (26.1)
No degree
1 (0.7)
1 (1.4)
51 (38.6)
34 (51.5)
4
3
98 (72.1)
46 (66.7)
Surgery
0.085
Prior sexual activity
0 (0.0) 0.813
14 (10.3)
8 (11.6) 0.637
41 (30.1)
23 (33.3) 0.054
26 (19.1)
22 (31.9) 0.665
4 (2.9)
1 (1.4)
0.963 123 (91.1)
63 (91.3)
pain/discomfort, and anxiety/depression. Each EQ5D domain is assessed by a single question with three levels of response indicating the severity of a patient’s problems in that particular domain. In addition, patients are asked to rate their general health state on a visual analog scale (EQ5D-VAS) of 1–100, with 1 representing the worst state and 100 representing the best imagined state.16 To assess patients’ current level of sexual functioning, the Female Sexual Functioning Index (FSFI) was used. It is a validated 19-item multiple-choice questionnaire for selfreporting six domains of sexual functioning in women: desire, arousal, lubrication, orgasm, satisfaction, and pain/ discomfort.17,18 A patient can score up to a total of 6 points in each domain. The six domain scores are combined to create a total score, which ranges from 1.2 to 36. A higher score represents better sexual functioning.17,18 To assess baseline sexual activity, the questionnaire asked, ‘‘Were you sexually active before your cancer diagnosis? Yes/No.’’ As an assessment of whether patients were sexually active at the time of questionnaire completion, responses to FSFI items 3–14 were analyzed. If a respondent put a 0, indicating no sexual activity, for 6 or more of these questions, she was considered not sexually active. Statistical Analysis
0.426
Karnofsky performance status 90 or 100 (vs. \ 90)
Yes
40 (58.0)
Other
Yes
Yes
0.802
Widowed
Open (vs. minimally invasive) Missing
12 (8.8)
Intervention—vaginal lubricant Yes Intervention—vaginal moisturizer
p
0.009
Intervention—sexual counseling
0.862
Marital status Married
Postgraduate degree
Yes
0.560
Anxiety Yes
Intervention—hormone replacement therapy Yes
0.290
High blood pressure Yes
IVRT (n = 69), no. (%)
0.657
White
Yes
No IVRT (n = 136), no. (%)
Intervention—vaginal estrogen
0.4538 (B4 vs. [4 years)
1–2
Characteristic
p
\0.001
Age (years)
TABLE 1 continued
The study was powered to detect a correlation between patients’ sexual functioning score (FSFI) and health state score (EQ5D-VAS). The statistical end point was defined on the basis of a study conducted at MSKCC of breast cancer patients which found a moderate correlation
S. Damast et al. TABLE 2 FSFI scores by treatment group
TABLE 3 EQ5D responses by treatment group p value for no IVRT versus IVRT
FSFI subdomain
No IVRT
IVRT
Control populationa
Desire
Mean (SD): 2.5 (1.3)
Mean (SD): 2.4 (1.3)
Mean (SD): 0.5585 4.3 (1.1)
Median (range): 2.4 (1.2–6.0)
Median (range): 2.4 (1.2–5.4)
Mean (SD): 2.6 (2.0)
Mean (SD): 2.2 (2.0)
EQ5D domain
No IVRT, n (%)
IVRT, n (%)
No problem walking about
111 (82)
52 (78)
Some problems in walking about
24 (18)
15 (22)
Confined to bed
0 (0)
0 (0)
No problem with self-care
128 (95)
65 (97)
Some problems washing or dressing myself
6 (4)
2 (3)
Unable to wash or dress myself
1 (1)
0 (0)
No problems with performing my usual activities
112 (83)
56 (84)
Some problems with performing my usual activities
20 (15)
11 (16)
Unable to perform my usual activities
3 (2)
0 (0)
No pain or discomfort
86 (65)
50 (76)
Some pain or discomfort
43 (32)
15 (23)
Extreme pain or discomfort
4 (3)
1 (2)
Not anxious or depressed
82 (61)
39 (58)
Moderately anxious or depressed
47 (35)
27 (40)
Extremely anxious or depressed
5 (4)
1 (2)
Mean
79.4
82.5
Median
85
88
Range
10–100
44–100
Mobility
Arousal
Median (range): 2.7 (0–6.0) Lubrication Mean (SD): 2.5 (2.2) Median (range): 2.1 (0–6.0) Orgasm
Pain
Median (range): 2.4 (0–6.0) Mean (SD): 2.2 (2.2)
Mean (SD): 0.3132 5.4 (1.1)
Median (range): 2.1(0–6.0)
Mean (SD): 2.7 (2.3)
Mean (SD): 2.6 (2.4)
Median (range): 3.2 (0–6.0)
Median (range): 2.4 (0–6.0)
Satisfaction Mean (SD): 3.1 (2.1)
Mean (SD): 0.1294 5.1 (1.1)
Mean (SD): 3.0 (2.0)
Median (range): 3.2 (0–6.0)
Median (range): 2.8 (0–6.0)
Mean (SD): 2.3 (2.5)
Mean (SD): 1.9 (2.3)
Median (range): 1.2 (0–6.0)
Median (range): 0 (0–6.0)
0.4345
Self-care
0.7206
Usual activities Mean (SD): 0.7443 5.1 (1.3)
Mean (SD): 0.8290 5.0 (1.2)
Mean (SD): 0.1806 5.5 (1.3)
A higher domain score represents better sexual functioning a
Control population refers to reported values in the FSFI validation study by Wiegel et al.18 based on a population of healthy women ages 20–74 years
between FSFI and EQ5D-VAS with a Pearson correlation coefficient of r C 0.24.19 On the basis of simulation data randomly sampled from the historical study, it was determined that 200 patients were needed to have 90 % power to identify a correlation of C0.24 between FSFI and EQ5DVAS using a two-sided test with significance level of 0.05. In total, 310 of the 451 mailed questionnaires were returned (173 surgery alone; 137 IVRT), for a response rate of 69 %. Before analysis, an additional 105 subjects were excluded: 55 subjects who completed fewer than 50 % of the items in the FSFI (32 surgery alone; 23 IVRT) and 50 subjects who were surveyed within 12 months of their hysterectomy (5 surgery alone; 45 IVRT). The latter group was excluded on the basis of published findings that sexual activity in EC survivors increases in the first year after surgery and then levels off.5,6 The total analyzed population was therefore 205 survivors who were more than 1 year after hysterectomy (136 surgery alone; 69 IVRT), or 45 % of the initial population queried.
p value for first level (no problem) versus second and third level
0.9118
Pain/discomfort
0.1131
Anxiety/depression
0.6836
EQ-Health State
0.2467
EQ-Health State is a visual analog scale ranging from 0 to 100, with a higher score representing better health state
Number and percentage were used to describe characteristics of the surgery-alone and IVRT groups, and the Chi square test (2-tailed) was used to compare characteristics between the groups. In cases of small numbers within a cell, Fisher’s exact test was used. EQ5D-VAS and FSFI scores were analyzed continuously, and correlation between EQ5D-VAS and FSFI scores was measured using Pearson correlation. These scores were summarized using mean, standard deviation, median, and range, and compared across groups using the Wilcoxon rank-sum test. Other variables were treated as categorical. Multivariate
Comparative Patient-Centered Outcomes in EC TABLE 4 Multivariate regression: FSFI and EQ5D (N = 198) Covariate
Estimated effect on FSFI
p
Model 1: FSFI Intercept
18.29 (15.61, 20.97)
Age [ 59 years (vs. 59 years or younger)
-2.64 (-5.86, 0.57)
0.1068
Radiation
0.32 (-3.03, 3.68)
0.8490
Open surgery (vs. MIS)
-3.50 (-6.54, -0.45)
0.0247
Model 2: EQ5D-VAS Intercept
83.35 (79.44, 87.25)
Age [ 59 years (vs. 59 years or younger)
-4.09 (-8.82, 0.64)
0.0894
Radiation
5.91 (1.01, 10.81)
0.0183
Open surgery (vs. MIS)
-5.53 (-10.01, -1.06)
0.0156
regression models were built to account for imbalances (defined as p \ 0.1) between the two treatment cohorts and to identify factors independently associated with sexual functioning and health state. Because so few women took hormone replacement therapy, it was not included in multivariate models. Backward selection was performed to eliminate variables with p values of[0.2, but radiation was included in every model because it was the variable of main interest. FSFI scores ranged from 1.2 to 36. On the basis of the study demonstrating the validity and reliability of the FSFI, a score of 26.5 was determined as the cut score to identify women with sexual dysfunction.18 All statistical analyses were performed by SAS version 9.2 (SAS, Cary, NC) and R 2.11.1 (The R Foundation for Statistical Computing, Vienna, Austria) software, and a p value of \0.05 was considered significant. RESULTS Demographic and Clinical Characteristics Characteristics of the analyzed patients according to treatment group are listed in Table 1. As shown in Table 1, the surgery-alone and IVRT groups were not different with respect to ethnicity, marital status, education level, medical comorbidities (diabetes, hypertension, anxiety), Karnofsky performance status, time from hysterectomy, and baseline sexual activity. However, the surgery-alone group was younger (p \ 0.001). Additionally, there was a trend toward more minimally invasive procedures in the surgeryalone cohort (p = 0.085). Rates of utilization of interventions for sexual functioning (hormone replacement therapy, estrogen, lubricant,
moisturizer, and counseling) were generally low and similar across groups. The only significant difference was that women who had IVRT were less likely to use hormone replacement therapy (0 vs. 8.8 %, p \ 0.01). Univariate Analyses and Correlation Between End Points Overall, 163 of 205 women (80 %) had FSFI \ 26.5, thereby meeting criteria for sexual dysfunction. This percentage was not different between the surgery-alone and IVRT groups (79 and 81 %, respectively, p = 0.7182). Mean FSFI scores were 15.7 (standard deviation 10.8) and 14.3 (standard deviation 10.7) in the surgery-alone and IVRT groups, respectively. All FSFI domain scores were low across both groups compared to a ‘‘norm’’ population, but there were no significant differences observed between the surgery-alone and IVRT groups (Table 2). The median EQ5D-VAS scores were 85 (range 10–100) and 88 (range 44–100) in the surgery-alone and IVRT groups, respectively. The majority of patients had excellent health states across all domains, with no significant differences between groups (Table 3). There was a significant correlation between the FSFI and EQ5D-VAS (r = 0.213, p = 0.0026), suggesting that those with improved sexual function had superior health state. Among sexually active women (n = 132), the correlation was stronger (r = 0.300, p = 0.0006).
Multivariate Analyses Multivariate regression was conducted to assess the impact of IVRT on both sexual function and health state (Table 4). Receipt of IVRT was not associated with FSFI score, p = 0.8490. Surgery-type was associated with FSFI score, p = 0.0247. Age [ 59 was associated with a 2.64point drop in FSFI score, but the effect was not significant. Receipt of IVRT was not associated with poorer health state; in fact there was a 5.91-point increase in EQ5DVAS, p = 0.0183, among those who had received adjuvant treatment. Open surgery was associated with a 5.53-point drop in EQ5D-VAS, p = 0.0156. After adjusting for radiation and open surgery, age [ 59 was associated with a 4.09-point lower EQ5D-VAS, but the effect was not significant (p = 0.0894).
Comparison of Sexual Activity Rates Between Groups The percentage of women who were sexually active at time of questionnaire completion in the surgery-alone
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group was 66.2 % (90 of 136) and in the IVRT group was 60.9 % (42 of 69). The percentage of women who were sexually active before treatment was 72.1 % (98 of 136) and 66.7 % (46 of 69), respectively. Of the women who were sexually active at baseline, the percentage that remained sexually active at time of survey was 77.6 and 71.7 %, respectively.
DISCUSSION The present study demonstrates several findings that may be useful in future survivorship studies as well as in clinical practice. First, a significant correlation between sexual functioning and health state was found, suggesting the importance of measuring sexual functioning as a component of health-related QOL in EC survivorship. Second, survivors of EC, regardless of treatment with adjuvant IVRT, were at risk for sexual dysfunction. Third, there did not appear to be an additional detriment to either health state or sexual function among patients who received IVRT compared to surgery alone. Last, although receipt of IVRT did not appear to be a treatment-related risk factor, minimally invasive surgery as compared to laparotomy was associated with improved health state and sexual function. Our main finding that IVRT does not negatively influence sexual health or health state among survivors of EC compared to surgery-alone contributes to the sparse knowledge concerning sexual health in EC survivorship. In a cross-sectional study from the University of Wisconsin of 72 EC survivors, 89 % met criteria for sexual dysfunction using the FSFI.13 RT was not found to be a significant contributing factor on multivariate analysis, although only 13 patients in this cohort had received RT. Investigators from Germany measured FSFI scores in 20 late survivors who had received IVRT and 20 who had undergone surgery alone; they found no difference in sexual functioning or quality of life between the groups.14 Similarly, researchers from Ohio State University mailed questionnaires to 16 IVRT and 53 surgery-alone patients; they found similar sexual outcomes between groups.15 These studies, in conjunction with the present one, indicate that receipt of IVRT itself is not a significant risk factor for poorer sexual functioning or quality of life in EC survivors, and therefore this notion should not be used as a reason to avoid IVRT in a patient who is otherwise an appropriate candidate.
It is interesting to compare these study results to similar end points reported among EC patients in the randomized PORTEC-1 and PORTEC-2 trials, which compared pelvic RT to observation, and pelvic RT to IVRT, respectively.4,6,20 There were no differences in sexual activity or functioning between patients treated with and without adjuvant radiation in PORTEC-1 and in the present study.20 The PORTEC-2 trial, however, found a 35 % rate of vaginal atrophy in IVRT patients and in a follow-up study, more vaginal dryness and less sexual enjoyment compared to an age-matched healthy control Dutch population.4,6 Notably, however, PORTEC-2 data was not compared to EC patients who were observed after hysterectomy. Our findings are thus not discordant. They support that there are significant problems with sexual functioning across all EC survivors when compared to a healthy normal population but suggest that there are no measurable differences in sexual functioning between those receiving and not receiving IVRT. Our secondary finding of improved health state and sexual functioning among those who received minimally invasive versus open surgery can be compared and contrasted to results from the LAP2 randomized clinical trial conducted by the Gynecologic Oncology Group, which compared laparotomy to laparoscopy for surgical staging of EC.21,22 While the LAP2 study, like ours, did find an association between minimally invasive surgery and improved QOL compared to open surgery, unlike ours, it failed to demonstrate a beneficial impact on sexual functioning.21,22 It may be that our discrepant findings are due to differences in time points at which the outcomes were measured (\6 months from hysterectomy in the LAP2 study vs.[1 year in the present study) or due to differences in response rates (41 % in the LAP2 study vs. 69 % in the present study). We hypothesize that different surgical techniques can lead to differences in adhesions, cosmesis, body image, and resultant sexual outcomes. Therefore, further prospective investigation into potential interactions between surgery type, radiation, and sexual functioning, especially in late survivorship, would be valuable. The low sexual functioning scores demonstrated in EC survivors in this study must be understood in a proper context. EC populations are generally older, and therefore multiple factors apart from their cancer diagnosis and treatment, such as age, partner status, and comorbid conditions, contribute to their overall poor sexual functioning.23,24 Yet despite these low scores, interestingly, a number of studies, like ours, have demonstrated a
Comparative Patient-Centered Outcomes in EC
positive correlation between sexual functioning and general health state in EC.13,22,25 Female sexual functioning is a complex process driven by many variables including age, partner issues, intimacy, psychological well-being, and physical changes. More research is therefore needed in order to better understand the relationship of the FSFI with other dimensions of sexuality including distress, and to prospectively study whether interventions designed to improve sexual functioning in female cancer patients will translate into improvements in overall QOL. Strengths of our study include the population size, the relatively high response rate, and the homogeneity of treatment received by patients, thus allowing us to draw specific conclusions concerning effects of IVRT on patientcentered outcomes. Conversely, findings of this study may not be generalized to all EC populations, as its design specifically excluded patients who had received pelvic RT, hormone therapy, and chemotherapy. There were several study limitations. It was not randomized, and therefore, there may have been unmeasured differences between the IVRT and surgery-alone groups. Potential factors not accounted for included body mass index, postsurgical nerve damage, extent of lymph node staging, and lymphedema. It is reassuring, however, that the EQ5D physical domains including mobility, pain, and ability to perform activities were equivalent between groups. Furthermore, because the women who received IVRT were more likely to have higher disease stage and grade, they were also more likely to have undergone lymph node staging; therefore, this would only strengthen our findings that despite more aggressive surgery, they did not score worse in either health state or sexual functioning. Because of the cross-sectional study design, we did not have a record of patients’ baseline sexual functioning
before any treatment. We addressed this by asking participants about pretreatment sexual activity; however, we acknowledge the possibility of recall bias. Last, it is possible that our study overestimates the degree of sexual functioning in EC survivors. As with any questionnaire study, one must account for response bias—that is, the possibility that those who responded were healthier or that there were differences in baseline demographic characteristics between those who responded and those who did not. Although our response rate of 69 % was strong, one might conjecture, on the basis of recent analysis of the LAP2 data, that those who did not return the survey were less likely to be sexually active and more likely to be older, unmarried, or in poor-quality relationships.22 Furthermore, we excluded from analysis those who were less than a year from hysterectomy and those who completed fewer than 50 % of items on FSFI. Therefore, caution should be used in applying these findings to early EC survivors (\1 year after hysterectomy) or to those who are not sexually active. In summary, sexual health is an important factor in early stage EC survivorship and correlates with health state. Our study suggests that women who undergo treatment for EC are at increased risk of sexual dysfunction regardless of whether they receive adjuvant IVRT. There does not appear to be a detriment to either health state or sexual functioning from IVRT compared to surgery alone. Further investigation into potential benefits of minimally invasive surgical techniques on sexual health of EC patients is merited. ACKNOWLEDGMENTS The authors wish to thank Laura Sit and Lauren Rogak for their contributions. DISCLOSURES Mario M. Leitao Jr. is a consultant for Intuitive Surgical. The other authors declare no conflict of interest.
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APPENDIX MSKCC Early Stage Endometrial Questionnaire Background Information Questions 1-5: General questions (1) Current age:
5 years
(7) Surgery Type:
Open hysterectomy
Laparoscopic hysterectomy
(8) Did you receive radiation therapy?
yes
no
(9) Did you receive chemotherapy?
yes
no
2 - 3 years
Robotic hysterectomy
Comparative Patient-Centered Outcomes in EC Questions 10-14: Questions about relationships, sexual health, and general well-being yes
no
(10)
Were you sexually active prior to your diagnosis?
(11)
Which of the following has affected your sexual health the most? (Check all that apply) Nothing
Cancer diagnosis
Change in relationship
Surgery
Husband unable
Anxiety
Age
Radiation
Other (please describe)________
(12)
Since recovery from cancer treatment, has your sexual health improved?
(13)
Have you used any of these interventions since your hysterectomy? (check all that apply) Hormone replacement therapy Vaginal moisturizer (eg. Replens)
(14)
yes
no
n/a
Topical estrogen (eg. Vagifem) Vaginal lubricant
Sexual health counseling
Right now, how is your general well being? 100%
I feel completely normal without any complaints or problems related to my disease
90%
I am able to carry on my normal activities, but I have minor symptoms
80%
I am able to carry on my normal activities with effort, and I have some symptoms
70%
I am able to care for myself, although I cannot carry on my normal activities
60%
I require occasional assistance although I can care for most of my own needs
50%
I require a lot of assistance and frequent care
40%
I am disabled and require special care and assistance
Female Sexual Function Index (FSFI) Ó Instructions: These questions ask about your sexual feelings and responses during the past 4 weeks. Please answer the following questions as honestly and clearly as possible. Your responses will be kept completely confidential. In answering these questions the following definitions apply:
Sexual activity can include caressing, foreplay, masturbation and vaginal intercourse. Sexual intercourse is defined as penile penetration (entry) of the vagina. Sexual stimulation includes situations like foreplay with a partner, self-stimulation (masturbation), or sexual fantasy.
S. Damast et al. CHECK ONLY ONE BOX PER QUESTION Sexual desire or interest is a feeling that includes wanting to have a sexual experience, feeling receptive to a partner’s sexual initiation, and thinking or fantasizing about having sex.
1. Over the past 4 weeks, how often did you feel sexual desire or interest? Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 2. Over the past 4 weeks, how would you rate your level (degree) of sexual desire or interest? Very high High Moderate Low Very low or none at all
Sexual arousal is a feeling that includes both physical and mental aspects of sexual excitement. It may include feelings of warmth or tingling in the genitals, lubrication (wetness), or muscle contraction. 3. Over the past 4 weeks, how often did you feel sexually aroused (“turned on”) during sexual activity or intercourse? No sexual activity Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 4. Over the past 4 weeks, how would you rate your level of sexual arousal (“turn on”) during sexual activity or intercourse? No sexual activity Very high High Moderate Low Very low or none at all 5. Over the past 4 weeks, how confident were you about becoming sexually aroused during sexual activity or intercourse? No sexual activity Very high confidence High confidence Moderate confidence Low confidence Very low confidence
6. Over the past 4 weeks, how often have you been satisfied with your arousal (excitement) during sexual activity or intercourse? No sexual activity Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never
Comparative Patient-Centered Outcomes in EC 7. Over the past 4 weeks, how often did you become lubricated (“wet”) during sexual activity or intercourse? No sexual activity Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 8. Over the past 4 weeks, how difficult was it to become lubricated (“wet”) during sexual activity or intercourse? No sexual activity Extremely difficult or impossible Very difficult Difficult Slightly difficult Not difficult
9. Over the past 4 weeks, how often did you maintain your lubrication (“wetness”) until completion of sexual activity or intercourse? No sexual activity Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 10. Over the past 4 weeks, how difficult was it to maintain your lubrication (“wetness”) until completion of sexual activity or intercourse? No sexual activity Extremely difficult or impossible Very difficult Difficult Slightly difficult Not difficult
11. Over the past 4 weeks, when you had sexual stimulation or intercourse, how often did you reach orgasm (“climax”)? No sexual activity Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 12. Over the past 4 weeks, when you had sexual stimulation or intercourse, how difficult was it for you to reach orgasm (climax)? No sexual activity Extremely difficult or impossible Very difficult Difficult Slightly difficult Not difficult
S. Damast et al. 13. Over the past 4 weeks, how satisfied were you with your ability to reach orgasm (climax) during sexual activity or intercourse? No sexual activity Very satisfied Moderately satisfied About equally satisfied and dissatisfied Moderately dissatisfied Very dissatisfied 14. Over the past 4 weeks, how satisfied have you been with the amount of emotional closeness during sexual activity between you and your partner? No sexual activity Very satisfied Moderately satisfied About equally satisfied and dissatisfied Moderately dissatisfied Very dissatisfied 15. Over the past 4 weeks, how satisfied have you been with your sexual relationship with your partner?
Very Satisfied Moderately satisfied About equally satisfied and dissatisfied Moderately dissatisfied Very dissatisfied 16. Over the past 4 weeks, how satisfied have you been with your overall sexual life? Very satisfied Moderately satisfied About equally satisfied and dissatisfied Moderately dissatisfied Very dissatisfied 17. Over the past 4 weeks, how often did you experience discomfort or pain during vaginal penetration? Did not attempt intercourse Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 18. Over the past 4 weeks, how often did you experience discomfort or pain following vaginal penetration? Did not attempt intercourse Almost always or always Most times (more than half the time) Sometimes (about half the time) A few times (less than half the time) Almost never or never 19. Over the past 4 weeks, how would you rate your level (degree) of discomfort or pain during or following vaginal penetration? Did not attempt intercourse Very high High Moderate Low Very low or none at all
Comparative Patient-Centered Outcomes in EC
By placing a tick in one box in each group below, please indicate which statements best describe your own health state today. Mobility I have no problems in walking about I have some problems in walking about I am confined to bed Self-Care I have no problems with self-care I have some problems washing or dressing myself I am unable to wash or dress myself Usual Activities (e.g. work, study, housework, family or leisure activities) I have no problems with performing my usual activities I have some problems with performing my usual activities I am unable to perform my usual activities Pain/Discomfort I have no pain or discomfort I have moderate pain or discomfort I have extreme pain or discomfort Anxiety/Depression I am not anxious or depressed I am moderately anxious or depressed I am extremely anxious or depressed
UK (English) © 1990 EuroQol Group EQ-5D™ is a trade mark of the EuroQol Group
S. Damast et al. Best imaginable health state 100
To help people say how good or bad a health state is, we have drawn a scale (rather like a thermometer) on which the best state you can imagine is marked 100 and the worst state you can imagine is marked 0. We would like you to indicate on this scale how good or bad your own health is today, in your opinion. Please do this by drawing a line from the box below to whichever point on the scale indicates how good or bad your health state is today.
Your own health state today
9
0
8
0
7
0
6
0
5
0
4
0
3
0
2
0
1
0
0 Worst imaginable health state
UK (English) © 1990 EuroQol Group EQ-5D™ is a trade mark of the EuroQol Group
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