Volume 120, Issue 14 p. 2215-2221
Original Article
Free Access

Cancer patients' perceptions regarding the value of the physical examination: A survey study

Kunal C. Kadakia MD

Kunal C. Kadakia MD

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

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David Hui MD, MSc

David Hui MD, MSc

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

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Gary B. Chisholm MS

Gary B. Chisholm MS

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas

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Susan E. Frisbee-Hume RN, MS, CCRC, OCN

Susan E. Frisbee-Hume RN, MS, CCRC, OCN

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

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Janet L. Williams MPH, CCRP

Janet L. Williams MPH, CCRP

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

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Eduardo Bruera MD

Corresponding Author

Eduardo Bruera MD

Department of Palliative Care and Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

Corresponding author, Eduardo Bruera, MD, Department of Palliative Care and Rehabilitation Medicine, Unit 1414, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; Fax: (713) 792-6092; [email protected]Search for more papers by this author
First published: 04 June 2014
Citations: 19

See related editorial on pages 2077–9, this issue.

Abstract

BACKGROUND

Despite its clinical utility, progressive reliance on technology can lead to devaluing the physical examination in patients with advanced cancer. The primary objective of this study was to determine whether these patients have a positive or negative perception of the physical examination. A secondary objective was to determine whether these perceptions are related to interpersonal/relational values (symbolic) or diagnostic/objective values (pragmatic).

METHODS

One hundred fifty patients with cancer who were receiving concurrent oncology and palliative care were administered a 26-item survey regarding their overall perception of the physical examination. The primary outcome—patient responses to “In the last 3 months, I believe my experience while being examined has been overall: very negative (a score of −5) to very positive (a score of +5),”—was analyzed using the Sign test. Other items were predefined as either symbolic or pragmatic statements, and patient responses from strongly disagree (a score of 1) to strongly agree (a score of 5) were further analyzed. Multivariable logistic regression was used to test for associations between baseline characteristics and the primary outcome.

RESULTS

Most patients (83%) indicated that the overall experience of being examined was highly positive (median score, 4; interquartile range [IQR], 2-5; P ≤ .0001). Patients valued both the pragmatic aspects (median score, 5; IQR, 4-5) and symbolic aspects (median score, 4; IQR, 4-5) of the physical examination. Increasing age was independently associated with a more positive perception of the physical examination (odds ratio, 1.07 per year; 95% confidence interval, 1.02-1.12 per year; P = .01).

CONCLUSIONS

Patients with advanced cancer indicate that the physical examination is a highly positive aspect of their care. These benefits are perceived as having both symbolic and pragmatic value. The physical examination should remain a cornerstone of clinical encounters. Cancer 2014;120:2215–2221. © 2014 American Cancer Society.

INTRODUCTION

The physical examination is a routine facet of almost all physician interactions. In the context of cancer care, physical examination can be an invaluable tool to help assess tumor response, narrow differential diagnoses, and lead to appropriate diagnostic testing and empiric treatment in the presence of new complaints. However, progressive reliance on modern investigative technology has reduced diagnostic confidence in the physical examination.1, 2

A survey of approximately 1200 patients who were receiving primary care indicated that the majority expected some intervention during their clinical encounter, such as undergoing laboratory testing, radiography, or a physical examination.3 It is noteworthy that patient satisfaction has been linked with the reception of expected services.4-6 Kravitz et al studied how patients value the role of diagnostic testing.7 This work postulates that a patient perceives an omitted intervention, such as the physical examination, in 2 distinct dimensions. The first is of pragmatic consideration in that testing might directly affect diagnostic, prognostic, or therapeutic assessments. The second dimension is of a symbolic nature and is described as the perception that diagnostic investigations might validate a patient's distress, demonstrate interest, and provide reassurance and clinical credibility.

Understanding the relational and interpersonal implications of the physical examination is imperative in the context of patients with advanced cancer, because this population has a high degree of emotional distress and symptom burden.8-10 These patients are routinely followed by multiple cancer care providers and undergo numerous diagnostic and therapeutic interventions throughout their cancer trajectory. It could be hypothesized that multiple physical examinations by different physicians during medical evaluation might negatively influence perceptions about their clinical experience. Therefore, it is essential to understand how the physical examination is associated with symptom distress and patient satisfaction. In contrast, it might potentially enhance the patient-physician bond through its ritualistic aspects2, 11 or the intimacy of physical contact itself.12 To our knowledge, there are no studies on how patients with advanced cancer perceive being routinely examined.

To improve the understanding of patient expectations, attitudes, and perceptions of the physical examination, we conducted a prospective survey in patients with advanced cancer. The primary objective was to determine whether these patients feel that the physical examination is an overall positive or negative aspect of their medical experience. Further objectives included determining whether these perceptions were related to symbolic or pragmatic factors and which factors were associated with a positive perception of the physical examination.

MATERIALS A ND METHODS

Study Design

From February 2, 2013 to May 1, 2013, we recruited inpatients and outpatients who were being followed by the Supportive Care team at the University of Texas MD Anderson Cancer Center. To be eligible, patients had to speak English, had to be aged ≥18 years, and had to have advanced cancer characterized as locally advanced, metastatic, or relapsed disease. Patients with delirium were excluded based on a Memorial Delirium Assessment Scale (MDAS) score of greater than 13 (of a possible score of 30) at the time of study enrollment. The Institutional Review Board of the University of Texas MD Anderson Cancer Center approved all study procedures.

Measures

We collected data on patients' sociodemographic information (age, sex, race, educational background), their clinical characteristics (cancer type, years since diagnosis, estimated of number of physical examinations during the previous 3 months), and symptom distress scores on the Edmonton Symptom Assessment Scale (ESAS), which has been validated and is reliable for assessing the intensity of symptoms in patients with cancer.13 All patients underwent evaluation for the presence of delirium based on the MDAS.

The survey was developed by the research team and consisted of 26 items (see Supporting Information). The purpose of the survey was to evaluate the responses of a broad cohort of patients with advanced cancer regarding their perceptions of the physical examination without the intention to develop a validated instrument or psychometric tool. Before study enrollment, 10 volunteers who were not involved with the study conception or design completed the survey, and the questions were edited based on general feedback.

We constructed Question 1 (Q1)—“In the last 3 months, I believe my experience while being examined has been overall: very negative (−5) to very positive (+5)”—to determine our primary objective. To further determine whether the perception of this experience was of a pragmatic or symbolic nature, 2 questions were predefined as being associated with pragmatic versus symbolic reasoning. Question 2 (Q2), the pragmatic statement, read: “I believe the physical examination allows my doctor to find out useful information about my health”; whereas Question 3 (Q3)—“I believe the physical examination shows me that my doctor cares about me”—served as the symbolic statement. With the exception of Q1, all items were presented as statements followed by a 5-point Likert-type scale (from strongly agree to strongly disagree). Fourteen of the remaining 23 items were developed to further characterize the symbolic/pragmatic aspects of the physical examination experience. The remaining 9 items were related to specific attitudes regarding the physical examination.

After informed consent was obtained, patients who participated in the survey answered the questions before evaluation by a supportive care specialist to remove the possible influence related to the current clinical encounter and examination. Patients were informed that their responses would be kept confidential from their medical care providers. To reduce the effect of observer bias, patients completed the survey independently; research assistants were available for questions if needed.

Data Analyses

We summarized sociodemographic information, clinical characteristics, symptom distress scores, and survey responses using descriptive statistics, including means, medians, interquartile ranges (IQRs), and estimates of error. One hundred fifty patients provided 80% power to detect an effect size as small as 0.23 (H0 [mean experience = 0] vs HA [mean experience ≠ 0]), based on a 2-sided, 1-sample t test, to test the primary objective that the patients' overall experience was either positive or negative when the type I error rate was 5% (NQuery 7.0; Statistical Solutions, Cork, Ireland). However, our observed results were not normally distributed; therefore, instead, we used a Sign test, for which the power to detect a difference from zero is expected to be somewhat less than that of the t test.

Secondary objectives were examined using multiple logistic regressions. Overall experience was the dependent variable, and independent variables consisted of demographic factors (age, sex, etc), clinical factors (cancer type, ESAS, etc), and Q2 and Q3 from the survey. Backward stepwise regression was performed based on those variables that were significant in univariate regressions at the 15% significance level.

Correlations between Q1, Q2, and Q3 scores and continuous baseline characteristics were tested using Spearman correlation coefficients. We tested for differences among levels of discrete characteristics with respect to Q1, Q2, and Q3 scores using the Mann-Whitney test. We tested differences in Q1 scores based on patients' pragmatic or symbolic perceptions. Based on the predefined pragmatic and symbolic questions, patients whose symbolic mean scores were higher than their pragmatic mean scores were classified as the group that viewed the physical examination as having more of a symbolic benefit, and those with higher pragmatic mean scores were classified as the group that viewed the physical examination as having more of a pragmatic benefit. On the basis of this classification, we performed a Mann-Whitney test comparing the 2 groups. Missing data were excluded from the final analysis.

The SAS 9.2 statistical software package (SAS Institute Inc., Cary, NC) was used for analyses. P values ≤ .05 were considered statistically significant.

RESULTS

Sample Description

Among 208 patients who were approached, 14 did not have advanced cancer or were cognitively impaired. Of 194 eligible patients, 44 declined participation, and 150 patients completed the survey. Among the surveyed patients, 147 were outpatient and 3 others were accrued from an inpatient setting. Table 1 indicates that the median patient age was 57 years, 53% of patients were women (N = 80), 75% were white (N = 113), and lung and breast were the most common cancers (32%; N = 48). Patient-reported median pain, depression, and anxiety scores (on a scale from 0 to 10) were 4 (interquartile range [IQR], 2-7), 1 (IQR, 0-4), and 2 (IQR, 0-4), respectively.

Table 1. Baseline Patient Characteristics, N = 150
Characteristic No. of Patients (%)
Age: Median [range], y 57 [23-83]
Sex: Women 80 (53)
Race
White 113 (75)
Hispanic 13 (9)
Black 19 (13)
Asian/other 2 (1)
Education
≤High school 70 (47)
Basic college education 50 (33)
Advanced degree 24 (16)
Cancer diagnosis
Breast 24 (16)
Lung 24 (16)
Head and neck 19 (13)
Gastrointestinal 17 (11)
Genitourinary 32 (21)
Other 34 (23)
Estimated no. of physical examinations in last 3 moa
0-5 74 (50)
5-10 38 (26)
10-30 23 (15)
>30 14 (9)
Assessment Scales Median Score [IQR]
ESAS (scale from 0 to 10)
Pain, N = 150 4 [2-7]
Fatigue, N = 149 5 [2-7]
Nausea, N = 149 0 [0-3]
Depression, N = 150 1 [0-4]
Anxiety, N =150 2 [0-4]
Drowsiness, N = 150 2 [0-5]
Shortness of breath, N = 150 1 [0-5]
Appetite, N = 149 3 [1-5]
Sleep, N = 147 4 [2-5]
Feeling of well being, N = 149 4 [2-5]
Spiritual pain, N = 146 0 [0-2]
Financial distress, N = 147 2 [0-5]
MDAS (scale from 0 to 30) 1 [0-2]
  • Abbreviations: ESAS, Edmonton Symptom Assessment Score; IQR, interquartile range; MDAS, Memorial Delirium Assessment Scale.
  • a The number of examinations was based on patient report.

Patients' Perceptions of the Physical Examination

Figure 1 illustrates that, for the vast majority of patients (N = 123; 83%), the overall experience of being examined was positive (median score, 4; IQR, 2-5; P < .0001). Fifteen patients (10%) noted a mildly positive experience (ie, a score of 1 or 2), 23 (16%) noted a moderately positive experience (ie, a score of 3), and 85 (57%) noted a very positive experience (ie, a score of 4 or 5). Twenty-four patients (16%) reported an overall neutral experience, and only 1 patient (0.7%) reported a negative experience. When assessing the pragmatic influence (Q2) of patients' experience, 142 patients (95%) agreed (ie, a score of 4 or 5) that the physical examination allowed their physician to gain useful information regarding their health. Similarly, the symbolic influence (Q3) of the patients' experience was largely positive, as 125 patients (83%) agreed (ie, a score of 4 or 5) that the physical examination suggested that their physicians cared about them.

Details are in the caption following the image
Patients' overall experience of the physical examination is illustrated. These results are based on responses to Question 1 of the patient survey: “In the last 3 months, I believe my experience while being examined has been overall: very negative (−5) to very positive (+5).” IQR indicates interquartile range.

Correlates of Overall, Pragmatic, and Symbolic Perceptions

The data provided in Table 2 indicate that patients who had less education, compared with those who had college or advanced degrees, perceived the physical examination as a more positive experience (median score, 4.5 [IQR, 3-5] vs 3.5 [IQR, 1-5]; P = .01). Patients with more depression, anxiety, spiritual pain, poor sleep, nausea, drowsiness, and a lower sense of well being were associated with a less positive perception of the physical examination, as indicated in Table 3. The composite symptom distress score was also associated with a less positive experience. No association was observed between sex, ethnicity, or pain and overall perception of the physical examination. Patients with higher levels of depression, drowsiness, and overall psychological distress scores were less likely to perceive that the physical examination allowed their physician to gain useful information regarding their health. Compared with whites, nonwhites were associated with a stronger perception that the physical examination suggested that their physicians cared about them (median score, 5 [IQR, 4-5] vs 4 [IQR, 4-5]; P < .01).

Table 2. Demographic Factors Associated With Overall, Pragmatic, and Symbolic Perceptions of Physical Examination
Q1: Overall Perceptionsa Q2: Pragmatic Perceptionsb Q3: Symbolic Perceptionsc
Variable No. Median (IQR) Pd No. Median (IQR) P No. Median (IQR) Pd
Sex
Women 78 4 (2-5) 80 5 (4-5) 80 4.5 (4-5)
Men 70 4 (2-5) .32 70 5 (4-5) .25 70 4 (4-5) .66
Ethnicity
White 112 4 (2-5) 113 5 (4-5) 113 4 (4-5)
Nonwhite 36 4 (2-5) .75 37 5 (4-5) .07 37 5 (4-5) <.01
Education
≤High school 70 4.5 (3-5) 70 5 (4-5) 70 5 (4-5)
Basic college or advanced degree 72 3.5 (1-5) .01 74 5 (4-5) .76 74 4 (4-5) .12
  • Abbreviations: IQR, interquartile range; Q, survey question.
  • a Question 1: “In the last 3 months, I believe my experience while being examined has been overall: very negative to very positive” (scale from −5 to +5).
  • b Question 2: “I believe the physical examination allows my doctor to find out useful information about my health” (scale from 1 to 5).
  • c Question 3: “I believe the physical examination shows me that my doctor cares about me” (scale from 1 to 5).
  • d P values in boldface indicate a statistically significant difference.
Table 3. Associations Among Symptom Burden and Overall, Pragmatic, and Symbolic Perceptions of Physical Examination
Q1: Overall Perceptionsa Q2: Pragmatic Perceptionsb Q3: Symbolic Perceptionsc
ESAS Symptoms r Pd r Pd r P
Pain −0.09 .25 −0.10 .21 0.02 .77
Fatigue −0.13 .12 −0.06 .49 −0.03 .75
Nausea −0.21 .01 −0.04 .66 −0.05 .55
Depression −0.24 <.01 −0.24 <.01 −0.12 .15
Anxiety −0.17 .04 −0.16 .06 −0.06 .47
Drowsiness −0.24 <.01 −0.17 .04 −0.14 .10
Shortness of breath −0.04 .59 0.04 .65 0.08 .32
Appetite −0.12 .13 0.05 .55 0.09 .30
Sleep −0.21 .01 −0.12 .15 −0.13 .12
Feeling of well being −0.23 <.01 −0.12 .15 −0.11 .20
Spiritual pain −0.21 .01 −0.10 .23 −0.09 .28
Financial distress −0.08 .36 −0.16 .05 −0.07 .42
Physical symptoms −0.19 .02 −0.06 .47 0.01 .91
Psychological symptoms −0.21 .01 −0.21 .01 −0.08 .34
Overall symptom distress −0.22 .01 −0.14 .09 −0.06 .47
  • Abbreviations: ESAS, Edmonton Symptom Assessment Score; Q, survey question; r, Spearman correlation.
  • a Question 1: “In the last 3 months, I believe my experience while being examined has been overall: very negative to very positive” (scale from −5 to +5).
  • b Question 2: “I believe the physical examination allows my doctor to find out useful information about my health” (scale from 1 to 5).
  • c Question 3: “I believe the physical examination shows me that my doctor cares about me” (scale from 1 to 5).
  • d P values in boldface indicate a statistically significant difference.

Associations Between Overall Perception and Baseline Characteristics

Multivariable modeling, as indicated in Table 4, suggested that increasing age was independently associated with a more positive perception of being examined (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.12; P = .01). When we applied pairwise comparisons for discrete demographic variables, patients who had a lower level of education, compared with those who had a college education, perceived the overall experience of being examined as more positive (OR, 4.4; 95% CI, 1.36-14.47; P = .01). A higher burden of spiritual pain was independently associated with a less positive perception of being examined (OR, 0.51; 95% CI, 0.36-0.73; P ≤ .01).

Table 4. Multivariable Logistic Regression of Select Baseline Characteristics and Perception of Physical Examinationa
Variable OR 95% CI P
Age (per y) 1.07 1.02-1.12 .01
High school (vs college as the reference category) 4.4 1.36-14.47 .01
Spiritual pain 0.51 0.36-0.73 <.01
  • Abbreviations: CI, confidence interval; OR, odds ratio.
  • a Univariable logistic regression analyses were run for each baseline variable—age, sex, ethnicity, symptom score, and education—to test for associations with dichotomized scores for Question 1 (overall perception), in which scores from −5 to 0 were defined as not liked (negative perception), and scores from 1 to 5 were defined as liked (positive perception). Variables that were significant at the 15% level in univariable analysis were included in the final multivariable model as noted.

Overall Patient Perceptions and Correlation with Pragmatic/Symbolic Preferences

We determined whether a patient viewed the physical examination more symbolically or pragmatically by comparing the patient's mean scores for the predefined pragmatic and symbolic statements; if the patient had a higher mean symbolic score, then he or she was classified as symbolic, otherwise the patient was classified as pragmatic (see online supporting information). The proportion of patients viewing the physical examination more symbolically was 48% (71 of 148 patients) compared with 52% (77 of 148 patients) who had a more pragmatic view (P = .62). Patients classified as symbolic, compared with pragmatic, perceived the physical examination as a more positive experience (median score, 5 [IQR, 3-5] vs 3 [IQR, 1-5]; P < .01; Wilcoxon rank-sum test).

Unique Attitudes Regarding Undergoing Physical Examination

The median patient responses to the 9 remaining questions related to specific attitudes regarding the physical examination are available online (see online supporting information). Men expected to be examined at each visit more often than women (median score, 4 [IQR, 3-4] vs 3.5 [IQR, 2-3]; P = .01). The belief that undergoing multiple physical examinations in 1 day could lead to increased anxiety occurred more often in patients with less education (median score, 3 [IQR, 2-4] vs 2.5 [IQR, 2-4]; P < .01). No difference in the responses to these statements was observed between ethnicities. Increased levels of pain, fatigue, and poor sleep were all weakly associated with the belief that being examined increases pain, with Spearman correlation coefficients of 0.19, 0.26, and 0.24, respectively.

DISCUSSION

To our knowledge, this is the first study to explore the value of the physical examination from the perspective of patients with advanced cancer. In this population, patients perceived the physical examination as a strongly positive aspect of their medical experience. The vast majority of cancer patients reported that being examined provided both symbolic and pragmatic meaning. How might these findings impact current physician practice?

Although clearly a clinically important aspect of medical care, the physical examination appears to have value beyond that of an investigative bedside tool. Patients felt that being examined had a strong symbolic meaning (ie, it provided reassurance, caring, and hope) as much as being a purely diagnostic aspect of their care. This is of particular importance, because patients with advanced cancer have a high degree of symptom distress.8, 9 It could be hypothesized that some cancer providers may want to spare patients with advanced cancer the perceived intrusiveness of the physical examination. The current survey suggests that patients with moderate symptom distress believe that being examined is important and do not believe it is overly intrusive. The symbolic influence of the physical examination might be related to the intimate aspect of touch itself12, 14; however, further research is needed to understand which other components of the examination provide reassurance and comfort.

Patients with greater spiritual pain, more depression and anxiety, and a lower sense of well being perceived being examined less positively than others. The reason for these findings remain unclear, and future qualitative research should be conducted to better characterize patient's beliefs related to diagnostic interventions, including physical examination. Patients with greater spiritual pain, depression, and anxiety are more likely to have an overall increased symptom burden.15, 16 One possible explanation for the current findings is that patients who report poor psychological well being are particularly vulnerable to any diagnostic intervention. This apprehension toward diagnostic testing has been observed in cancer patients who have poor coping strategies.17, 18 Therefore, it is imperative to use appropriate communication skills (eg asking permission and providing reassurance) before, during, and after examining patients with advanced cancer to decrease any associated distress.

Increasing age was identified as an independent predictor of a more positive perception of the physical examination. Inappropriate cancer screening occurs in a substantial proportion of older adults with advanced cancer19; it appears that the current survey provides preliminary evidence that this patient subgroup believes that the examination is particularly meaningful and may provide an avenue for discussion to avoid unnecessary screening tests. Patients who had less education, compared with those who had advanced schooling, indicated that, overall, being examined was a more positive experience. Studies have demonstrated clear differences between cancer outcomes among socioeconomically disparate populations.20-22 The observations in the current study suggest that these subgroups may have different expectations of diagnostics tests, and qualitative research is warranted to explore this further. It is noteworthy that there were no particular negative attitudes toward the physical examination independent of race or sex.

It has been suggested that more recent medical graduates have become less versed in physical examination, which, in turn, can lead to unnecessary testing and can affect patient satisfaction.23, 24 In response, an increase in educational efforts to improve bedside diagnostic skills has developed.25-28 It is conceivable that the rapid progress and evolving reliance on diagnostic testing in the era of personalized cancer medicine may make time-constrained cancer providers devalue the physical examination as well. Awareness of specific patient expectations during clinical encounters can increase patient satisfaction.6, 29, 30 Therefore, the observations in this study suggest that the physical examination should not be minimized in patients with advanced cancer, because it is perceived as a highly positive aspect of their care.

The findings of this study must be interpreted in the context of potential limitations. A major limitation is the cross-sectional design, which precludes causality to the associations reported. All participants were receiving multidisciplinary care at a tertiary cancer center and were primarily outpatients, which decreases the generalizability of the current findings to the community and inpatient settings, respectively. Because the entire cohort was receiving supportive services at an institution with a well developed palliative care program, selection and referral bias could further decrease the generalizability of the findings. However, most patients who are referred to this Supportive Care Center receive active cancer treatment, suggesting that the findings may be representative of patients receiving standard oncologic care.8 Although not directly assessed in this cohort, patients with other advanced illnesses may have comparable beliefs, because it has been demonstrated that these patients have similar physical and psychological symptom burden and share common values with patients who have advanced cancer.31-34 Because only patients with advanced cancer were included, these findings are not generalizable for patients earlier in their cancer trajectory and warrant further evaluation. Although there were differences observed in the overall physical examination experience between patients who perceived the physical examination as more symbolic rather than pragmatic, the absolute difference was relatively small. Qualitative research may be needed to better characterize the values that influence patient perceptions related to the physical examination, as discussed above. These findings should be replicated in the context of a longitudinal study. We also conducted multiple statistical testing; therefore, any statistical findings should be viewed as exploratory and warrant further examination.

Despite the aforementioned limitations, this survey provides robust evidence that patients with advance cancer find the physical examination to be a highly positive aspect of their care. This benefit appears to be associated with both symbolic and pragmatic meaning. Thus, as sophisticated diagnostic testing and personalized cancer medicine continue to evolve and improve patient outcomes, the physical examination should remain a cornerstone of all clinical encounters.

FUNDING SUPPORT

This work was supported in part by National Institutes of Health grants RO1NR010162-01A1, RO1CA122292-01, and RO1CA124481-01 (to E.B.). This work also was supported in part by The University of Texas MD Anderson Cancer Center Support Grant (CA 016672).

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.