Assessment of physical function by subjective and objective methods in patients undergoing open gynecologic surgery

Abstract

Objective:

To evaluate the utility of patient-reported outcomes (PROs) to measure physical functioning in perioperative care for patients with gynecological (GYN) tumors.

Methods:

180 patients with GYN tumors undergoing open surgery participated in this longitudinal study. The physical functioning was measured by a subjective PRO tool, the Interference subscales of the MD Anderson Symptom Inventory (MDASI-I); as well as by an objective tool, the Timed Up & Go test (TUGT), perioperatively. Longer time (>20 seconds) needed to complete the TUGT was defined as “Prolonged”. Patients completed EuroQoL-5D as well. The association between the scores of MDASI-I items and TUGT was assessed via the Spearman correlation coefficient. The known-group validity was assessed using the t-test and Cohen’s D effect size.

Results:

Compliance rates at preoperative, discharge and postoperative time points of MDASI-I were 98%, 95%, 96%; while TUGT completion rates were 92%, 75%, and 80%, respectively. Patients who had refused TUGT at discharge reported a significantly worse “MDASI-general activity” score compared to patients who completed TUGT (mean score of 7.00 vs. 5.38, P=0.020). Patient-reported “Walking” on MDASI-I significantly differentiated patients with prolonged vs. those with frail/normal TUGT at discharge (mean score of 4.89 vs. 2.79, Cohen’s d effect size = 0.82, P < 0.001) MDASI-I demonstrated excellent known-group validity per performance status and for the EuroQoL-5D subscales.

Conclusion:

Patient-reported physical functioning impairment after GYN surgery correspond with observed worse scores of the objective functioning measure test (TUGT). MDASI-I assessment represents a feasible and valid tool to evaluate functional status and warrants further implementation in the perioperative setting.

Introduction

Recovery from major abdominal surgery for gynecologic (GYN) tumors is usually characterized by a combination of physical impairments and psychological challenges that impact the trajectory of recovery and the timing of receipt of adjuvant cancer therapies after surgery. Thus, there is increasing awareness and effort to accelerate functional recovery, minimize symptom burden and improve quality of life (QoL) through enhanced recovery after surgery (ERAS) programs [1–4]. In the era of ERAS and “fast-track” recovery programs, functional recovery has been listed as the most important target of successful perioperative care from the professionals’ point of view [5,6] and a vital and a vital patient-centered outcome after surgery [7].

For patients undergoing surgery, incorporating patients perception into perioperative care metrics is vital [8, 9] [10, 11]. Capturing different aspects of health status and assessing physical capabilities typically require objective and subjective validated measurement tools [12–14]. Timed performance-based validated tools for measuring the physical activities [15, 16] have been used as objective measures after surgery. However, they are labor and time-intensive to perform. Patient-reported outcomes (PROs), as subjective measures, have become increasingly utilized to assess the efficacy of ERAS pathways [17–20]. PROs have the ability to capture the multidimensional aspects of recovery, including physical and functional capabilities, as well as emotional and social aspects [7, 12, 14, 21–23].

Perioperative tracking and proactive management of functional status, using real-time PROs can enhance surgical recovery [10, 24–27]. Tracking PROs perioperatively in patients undergoing surgery for GYN tumors has been explored [26–30]. Yet, systematic evaluations of PROs as surrogates for objective measures of physical/functional recovery status in patients undergoing surgery for GYN tumors are lacking.

In this study we assessed the physical function by a validated subjective PRO assessment tool, the interference subscale of MD Anderson Symptom Inventory (MDASI-I) [31] and by an objective measurement tool, Timed Up & Go test (TUGT), to evaluate the utility of PROs to measure physical functioning in perioperative care for patients with GYN tumors.

Methods

Sample

The study was approved by the Institutional Review Board of The University of Texas MD Anderson Cancer Center. Patients were consecutively recruited from the MD Anderson Gynecologic Oncology Center between 2018–2019. Eligible patients were required to be at least 18 years old, speak English, and scheduled to undergo an exploratory laparotomy for a known or suspected GYN tumor. All patients provided written informed consent.

A trained study coordinator contacted the eligible patients to complete self-administered questionnaires and objective measures. The study coordinator also collected information (demographics, current disease, and treatments) from medical records. The Charlson comorbidity index [32] was collected from the medical charts. The performance status was evaluated by research staff, using the Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) [33].

PRO physical functioning measure

We previously developed and psychometrically validated the MDASI-PeriOp-GYN module for patients undergoing surgery with GYN tumors [34]. Besides symptom items (13 core items and 10 GYN module items), the MDASI-I [35] captures physical interference items (general activity, work, and walking) and psychological interference items (mood, relation with others, and enjoyment of life). MDASI-I was rated with a 24 h recall period on a 0–10 scale; with “10” indicating “Interfered Completely”. MDASI-I scores were collected preoperatively daily during hospitalization, by discharge day from the hospital, and weekly up to 6 weeks after discharge. Patients rated MDASI-I before surgery, daily in hospital, days 3 and 7 after discharge then weekly up to 6 weeks.

Patients also rated EuroQoL-5 Dimensions (EQ-5D) [36] at three time points, preoperatively, by discharge day from hospital, and during postoperative clinic visit. EQ-5D measures the health status in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Objective physical functioning measure

TUGT [37, 38] was assessed at three time points, preoperatively, by discharge day from hospital, and during postoperative clinic visit. It measures the time it takes a participant to rise from a chair, walk 3 meters, turn, walk back, and sit down again. TUGT, as a performance outcome measurement tool, was assessed preoperatively, by discharge day, and at the first postoperative outpatient follow-up visit. . A final score was recorded as the mean score of two attempts of TUGT at each time points and was categorized into 3 groups (normal (≤10 s), frail (11–20 s), and prolonged (needs further evaluation) (>20 s), based on literature. TUGT > 20 s has been associated with clinically meaningful poor outcomes such as falls [36–38]

Statistical Analysis

Sample size for this prospective study was determined based on a previous longitudinal study that utilized PROs to assess the functioning status in patients post thoracic surgery [24]. Descriptive statistics are shown as mean, standard deviation, median, minimum and maximum for continuous variables, and percent for categorical variables. The comparative analysis of the MDASI-I and TUGT was conducted in patients who completed both PROs and the objective measures on physical functioning at each of the three perioperative time points. To examine the known-validity of the MDASI-I items, t-test and Cohen’s D effect size were used to test the ability of MDASI-I scores to differentiate patients with good ECOG PS (0–1) vs, poor (2–4), patients with level 1 EQ-5D vs. those with level 2–5, as well as patients within each TUGT group. Kruskal Wallis Test was used to compare more than two groups. Spearman correlation coefficient was also used to assess the association between the severity of MDASI-I scores and prolonged TUGT final scores.

All statistical procedures were performed using SAS statistical software, version 9.4 (SAS Institute, Cary, NC). All P values reported are 2-tailed. Statistical significance was set at P<0.05.

Results

Sample

Overall, 180 patients who underwent exploratory laparotomy and additional gynecologic procedures were included in this analysis. Of these, 16 patients were diagnosed with a benign condition, primarily fibroids or benign ovarian masses. There was no significant difference for patients with cancer or benign tumor regarding preoperative ECOG performance status, length of hospital stay, estimated blood loss, or 30 day complication rates. However, patients with benign tumors were significantly younger than patients with cancer (50 vs. 57 years old, P=.03), and with chronic pain history (37.5% vs. 13.4%, P=.02). All patients received care under the ERAS pathway. Approximately 75.6% (136) of the patients had no major comorbidities at baseline. Table 1 represents patient and treatment characteristics.

Table 1.

Patient, treatment and disease characteristics

	Mean (std)	Median (min, max)
Age (years)	56.4 (13.1)	58 (25, 83)
Length of Stay (days)	3.3 (1.6)	3 (1, 10)
Surgical Time (minutes)	250.8 (83.4)	240 (72, 503)
Estimated Blood Loss (mL)	383.9 (422.8)	250 (20, 2500)
Baseline MDASI Pain	1.61 (2.57)	0 (0, 10)
	N (%)
Ethnicity
Hispanic or Latino	36 (20)
Not Hispanic or Latino	143 (79.44)
Race
White or Caucasian	145 (80.56)
Black or African American	12 (6.67)
Asian	8 (4.44)
Other	15 (8.84)
Marital Status
Married	119 (66.11)
Single	24 (13.33)
Divorced	17 (9.44)
Widowed	16 (8.89)
Others	4 (2.22)
ECOG PS Pre-surgery*
0	122 (67.78)
1	46 (25.56)
2	9 (5.00)
3	3 (1.67)
Charlson Comorbidity Index
0	22 (12.22)
1	22 (12.22)
2	45 (25.00)
3	49 (27.22)
4+	42 (23.34)
History of Chronic Pain
No	151 (83.89)
Yes	28 (15.56)
Current Tumor
Malignant - Primary	130 (72.22)
Malignant - Recurrent	21 (11.67)
Benign	16 (8.89)
Neoplasm of Low Malignant Potential	9 (5.00)
Malignant - Dual Primary	4 (2.22)
Epidural
No	180 (100%)
Transversus Abdominus Plane (TAP) Block
No	180 (100%)
Chronic use of opioids
No	170 (94.4%)
Yes	10 (5.56%)

^*ECOG PS: Eastern Cooperative Oncology Group Performance Status Scale

Longitudinal Measuring Physical Functioning Status: Data Availability

There were 178 patients who were assessed by both TUGT and MDASI before surgery, 169 on the day of discharge, and 172 at their postoperative outpatient follow-up visit. The average time elapsed from surgery to the outpatient postoperative assessment of TUGT was about 1 month after surgery (29.1 + 10.8 days). The availability of both MDASI-I and other PROs data was excellent, with 99% (178/180) of patients completing the PRO instruments at the preoperative time point, 95% (171/180) by hospital discharge, and 95.6% (172/181) at the postoperative outpatient clinic follow-up. The completion rate of TUGT at the three time points was 91.7% (165/180 patients at the preoperative time point), 74.6% (126/169 patients by day of discharge), and 80.2% (138/172 patients at the postoperative clinic follow-up).

At the preoperative baseline assessment, the reasons for missing TUGT included severe physical function impairment (using wheelchair) so that they did not attempt the TUGT (2/15 patients), time constraints (7/15 patients), patient refusal (3/15 patients), and unknown reasons (3/15). The most common reason for missing TUGT data on the day of discharge (27/43 patients) was patient refusals. The majority of missing TUGT data at the outpatient postoperative visit (25/34 patients) was due to patients cancelled their clinic appointment.

TUGT and PROs Functioning Report: Objective and Subjective Measures

For the objective functioning measure, Table 2 presents the mean score of averaged TUGT scores (final scores) in seconds on the two attempts at each of the three assessment time points and by TUGT grouping (normal, frail and prolonged time). Spearman correlation showed that the severity of patient-reported “Walking” interference on MDASI-I was significantly associated with prolonged TUGT score at all three time points (all P < 0.01).

Table 2.

The Objective measure of physical functioning by the severity and compilation of TUGT (in seconds) and by proportion of patients among the TUGT groups at the three assessment time points.

TUGT (Median Days from Surgery [Q1, Q3]ǂ)	Total sample		% by TUGT grouping
	Completed Rate % (n/N)	Mean TUGT Score (SD) (seconds)*	Normal (≤ 10 seconds) N (%)	Frail (11 to 20 seconds) N (%)	Prolonged (>20 seconds) N (%)
Pre-operative baseline (−1 [−3, −1] days)	91.7% (165/180)	9.73 (2.54)	108 (65.45%)	55 (33.33%)	2 (1.21%)
Hospital Discharge (3 [2, 4] days)	74.6% (126/169)	18.12 (13.51)	7 (5.56%)	92 (73.02%)	27 (21.43%)
Post-operative clinic visit (27 [20, 34] days)	80.2% (138/172)	10.07 (3.35)	79 (57.25%)	57 (41.3%)	2 (1.45%)

^*mean of two tests at each time point

^ǂQ1, first quartile; Q3, third quartile

TUGT, Time up & go.

Figure 1 shows the trajectory of MDASI-I scores during the study period.

Figure 1.

The trajectory of interference subscales of MD Anderson Symptom Inventory in patients with gynecologic tumors who underwent open surgery

For the subjective functioning measures at discharge, the mean scores of the MDASI-walking item were statistically different across TUGT groups, Table 3. Specifically, higher mean severity of interference with walking item of MDASI-I was observed in patients with TUGT of >20 seconds compared to those with <=20 seconds at discharge (2.79 vs 4.89, ES=0.96, p=0.0004). There was also an observed significant difference in patient-reported scores of the general activity item of MDASI-I between patients who completed TUGT versus those who refused (mean severity 7.00 vs. 5.38, P=.0204, ES=0.65).

Table 3.

MDAS1-I scores by TUGT groups at discharge and post-operative follow-up time points.

Time points (average days from surgery)	MDASI-I	Mean MDASI-I Scores by TUGT grouping						P-value
		Normal + Frail (≤20 s)			Prolonged (>20 s)
		N	Mean	SD	N	Mean	SD
Discharge (3.1 ± 1.1 days)	Activity	99	5.14	3.24	27	6.26	2.51	0.1020
	Work	95	5.45	3.89	27	6.59	3.89	0.1544
	Walking	99	2.79	2.46	27	4.89	2.64	0.0004
		Did not complete TUGT due to patient refusal			Completed TUGT
Discharge (3.1 ± 1.1 days)	Activity	24	7	2.84	126	5.38	3.12	0.0204
	Work	23	6.17	3.86	122	5.7	3.91	0.6635
	Walking	25	3.72	3.01	126	324	2.63	0.4719

Time points (Average Days from Surgery)	MDASI-I	Mean MDASI-I Scores by TUGT grouping												P-value
		Did not complete TGUT			Normal			Frail			Prolonged
					(≤10 s)			(11 to 20 s)			(>20 s)
		N	Mean	SD	N	Mean	SD	N	Mean	SD	N	Mean	SD
Discharge (3.1 ± 1.1 days)	Activity	40	6.08	3.28	7	3.86	3.29	92	524	3.23	27	6.26	2.51	0.1474
	Work	37	5.89	3.93	6	2.33	1.75	89	5.66	3.91	27	6.59	3.89	0.1261
	Walking	41	3.46	2.96	7	0.71	1.25	92	2.95	2.46	27	4.89	2.64	0.0006
Post-operative follow-up (29.1 ± 10.8 days)	Activity	34	3.06	3.12	77	2.32	2.48	56	2.73	2.59	2	3.50	4.95	0.0331
	Work	34	3.35	2.84	76	2.36	2.62	56	2.95	2.75	2	4.00	5.66	0.0823
	Walking	34	2.18	2.92	77	1.18	1.9	56	1.86	2.2	2	3.50	4.95	0.0544

MDAS1-I: interference items of MD Anderson Symptom Inventory module. TUGT: time up & go test

By objective functioning measures at the postoperative time point (average of 4 weeks), 57% of patients were in the normal TUGT group. Patients with TUGT of >10 seconds reported a slightly higher score on the interference with the walking item of MDASI-I compared to those with TUGT of ≤10 s, yet that was not statistically significant (p = 0.0535). Patients who refused to complete the TUGT had significantly higher scores on interference with general activity of MDASI-I (P = 0.02).

At discharge, patients who completed the TUGT in >20 seconds reported more severe scores of shortness of breath on the MDASI module (2.3 vs. 0.82, ES=0.62, P=0.0125) compared to patients who completed the TUGT in ≤20 s. At the postoperative clinic visit time point, patients who refused to complete TUGT had higher fatigue scores on MDASI module (5.4 vs. 1.93, p=0.0132) compared to patients who completed the TUGT.

Validity of MDASI-I by EQ-5D subscales and ECOG Performance Status

Finally, MDASI-I also demonstrated excellent validity in discriminating patients with good versus poor ECOG performance status, and those with level 1 versus level 2–5 of mobility and activity subscales of EQ-5D at all three time points, Table 4.

Table 4.

Validity of MDASI-I items scores by EQ-5D subscales and ECOG PS levels

	Time period	MDASI-I items	No problem (level 1)			Problem (level 2 – 5)			P-value
			N	Mean	SD	N	Mean	SD
Mobility (EQ-5D)	Pre surgery	Activity	118	1.46	2.29	53	2.83	3.08	0.0020
		Work	118	1.42	2.27	53	2.85	3.27	0.0056
		Walking	118	0.62	1.55	53	2.79	2.78	<.0001
	Discharge	Activity	45	4.24	3.57	110	6.06	2.86	0.0016
		Work	40	3.5	3.88	109	6.51	3.57	0.0001
		Walking	45	1.67	2.39	111	3.95	2.58	<.0001
	Post discharge	Activity	109	1.89	2.23	56	4.11	2.9	<.0001
		Work	108	2.07	2.3	56	4.2	3.03	<.0001
		Walking	109	0.79	1.66	56	3.34	2.47	<.0001
Self-care (EQ-5D)	Pre surgery	Activity	158	1.66	2.44	14	4.21	3.51	0.0056
		Work	158	1.73	2.62	14	3.14	3.21	0.0781
		Walking	158	1.13	2.09	14	3.07	3.08	0.0060
	Discharge	Activity	47	4.17	3.74	105	6.1	2.71	0.0012
		Work	43	2.98	3.58	103	6.84	3.4	<.0001
		Walking	48	1.75	2.54	105	3.99	2.52	<.0001
	Post discharge	Activity	138	2.2	2.44	27	4.89	2.75	<.0001
		Work	138	2.35	2.52	26	5.19	2.77	<.0001
		Walking	138	1.18	1.86	27	4.07	2.85	<.0001
Activity (EQ-5D)	Pre surgery	Activity	101	1.2	2.16	71	2.83	2.93	<.0001
		Work	101	0.93	1.96	71	3.15	3.04	<.0001
		Walking	101	0.45	1.24	71	2.48	2.76	<.0001
	Discharge	Activity	16	2.88	3.86	135	5.84	2.91	0.0017
		Work	13	1.62	2.84	133	6.16	3.69	0.0001
		Walking	16	0.88	2.28	136	3.58	2.62	<.0001
	Post discharge	Activity	53	0.98	1.91	111	3.43	2.65	<.0001
		Work	53	0.98	1.56	110	3.68	2.79	<.0001
		Walking	53	0.75	1.86	111	2.08	2.39	<.0001
			Good (0–1)			Poor (2–4)
ECOG PS	Pre surgery	Activity	167	1.66	2.44	11	4.82	3.74	0.0007
		Work	167	1.62	2.49	11	5.09	3.62	0.0010
		Walking	167	1.05	1.92	11	4.82	3.74	0.0001
	Discharge	Activity	18	3.39	2.77	139	5.88	3.09	0.0011
		Work	17	3.41	3.02	134	6.05	3.9	0.0155
		Walking	18	1.39	2.03	140	3.62	2.69	0.0007
	Post discharge	Activity	123	2.19	2.38	22	5.09	2.81	<.0001
		Work	122	2.3	2.49	22	5.27	2.76	<.0001
		Walking	123	1.14	1.8	22	4.68	2.7	<.0001

ECOG PS: Eastern Cooperative Oncology Group Performance Status Scale, MDASI-I: interference items of MD Anderson Symptom Inventory module, EQ-5D: EuroQoL-5D.

Discussion

This study demonstrates the utility of a subjective PROs functioning assessment tool, MDASI-Interference, as a surrogate or potential substitution for an objective-timed performance test (TUGT) to predict patient’s physical functioning both pre and postoperatively through a longitudinal study of patients undergoing laparotomy for GYN tumors. Similar to other studies that indicated that a time of over 20 seconds on TUGT was associated with a need for physical assistance [39–41], in this study, we found that the interference with walking score of the MDASI-I items was significantly associated with a clinically-meaningful decrease in functional status (prolonged TUGT > 2o seconds) at the day of discharge from the hospital.

TUGT [37, 38] is one of the most commonly used, reliable, simple, and noninvasive physical functioning assessment tools that has been used in cancer and non-cancer settings [42–44]. For this reason, we chose the TUGT as the objective comparator to assess the sensitivity of the MDASI-I in assessing functional recovery. Our study provides evidence that collecting PROs at critical time points to monitor the patient’s functional status is feasible, with high compliance rates of 99% at the preoperative time point, 95% at discharge and 95.6% at the postoperative follow-up time points. Meanwhile, many patients refused or failed to complete TUGT by discharge (25%) and/or postoperatively (20%), either due to poor functioning status or secondary to canceled postoperative appointments. Non-completion of TUGT in this study sample correlated with patient’s report of more severe symptom interference on general daily activities postoperatively Furthermore, patients who refused to complete the TUGT reported a significantly higher severity of fatigue and shortness of breath on the MDASI, which directly correlated with impaired physical functioning status.

The concordance we identified between objective and subjective functioning assessment tools is crucial to support utilizing PROs to assess the physical status and functional recovery in patients after surgery [13]. The excellent known-group validity against the levels of EQ-5D and ECOG PS further confirms the feasibility and reliability of using MDASI-I items to measure the functional status in patients with GYN tumors undergoing open surgery. Such findings strongly support the validity of using MDASI-I items to measure functional status in perioperative care for patients with GYN tumors undergoing open surgery. Specifically, the “Walking” item of the MDASI-I appears promising and warrant further study for testing its sensitivity and specificity as a surrogate of functioning status when it is impractical to do objective tests, such as the TUGT.

Current literature supports patient empowerment through integration of the patient’s voice into medical care via using real-time PRO monitoring. PRO assessment coupled with responsive interventions have the potential to improve the quality of perioperative symptoms management in cancer patients [45, 46], and enhance functional recovery after surgery [10, 24–27, 28, 47]. Shi et al. showed that MDASI-I items are valid measures of symptom-related functional impairment. This interference item subscale is comparable to existing subjective assessment tools for physical functioning status among patients receiving cancer treatment [48, 49]. Further, previous research emphasizes that repeated longitudinal monitoring of PROs could predict and facilitate the functional recovery status after oncologic surgery [24, 25, 50].

This study has several limitations. The drop-out rates of the TUGT at discharge (mostly physically not able to), and the first postoperative follow-up (mostly due to patients not attending their scheduled postooperative evaluation in clinic) were higher than expected. However, even with the 75–80% of contribution rates at these two time points, we were able to achieve sufficient power of 0.8 to detect a median effect difference. This lends confidence to the validy of the results. Also, given that this was a real world study, we could not exactly control when patients would return for postoperative assessment. However, the wide SD of the timing of postoperative visit (11 days) is not relevant to our primary outcome (which was to compare the objective and subjective measure of functional recovery). Additionally, this study is a single-institution study, where the majority of the patients are non-Hispanic White. Further study should be conducted in multiple centers with diverse patient samples to confirm our findings. Howevere, a previous study of PROs in diverse patient samples with different cancer supports the external validity of the MDASI-I [51].

In conclusion, monitoring of perioperative physical functioning using the validated PRO tool, (MDASI-I items), demonstrated higher compliance and ease of administration compared to the TGUT objective measurement. Using such PRO tool may increase the ability of researchers and clinicians to consider functional recovery after surgery and to identify patients who may be at higher risk for falls or prolonged recovery after surgery. The broader impact of routine PROs monitoring to assess functional recovery after surgery and return to adjuvant oncologic treatments warrants further investigation.

Highlights.

• Postoperatively, compliance with the MDASI-I was better than with the objective measure Time Up & Go test (TUGT).

• Walking item of MDASI-Interference significantly differentiated the severity of prolonged TUGT in a clinically relevant way.

• MDASI-I scores showed an excellent known-group validity

• MDASI-I module is a valid and reliable tool to assess the physical functioning status after GYN surgery.