The evolution of uncertainty in second opinions about prostate cancer treatment

Abstract Background People who have cancer increasingly seek second opinions. Yet, we know little about what motivates patients to seek them and how beneficial they are. Uncertainty—experienced by patients or communicated by physician and patient—may be crucial throughout the second opinion process. Objective This study sought to investigate (1) how uncertainty influences men with prostate cancer to seek second opinions and (2) how second opinions may affect these patients’ sense of uncertainty and subsequent experiences with their care. Methods A qualitative study using semi‐structured interviews was performed. Men with localized or advanced prostate cancer (n=23) were interviewed by telephone about their motivations and experiences with seeking second opinions and the uncertainties they experienced. Analysis was performed using the constant comparative method. Results Patients sought second opinions because they were uncertain about receiving too little or biased information, experienced insufficient support in coming to a treatment decision, or because physicians expressed different levels of uncertainty than they did (“unshared uncertainty”). Uncertainty was reduced by the second opinion process for most patients, whereas for others, it increased or was sustained. This evolution depended on the way uncertainty was addressed during the second opinion consultation. Conclusions Second opinions may be a useful tool for some but not all patients. They should be used judiciously and not be viewed as a solution for current limitations to health‐care organization. An important yet challenging task for physicians is to focus less on information per se and more on how to assist patients manage irreducible uncertainty.


| INTRODUCTION
When confronted with a serious disease, patients may request a second opinion: soliciting the assessment of a diagnosis or treatment proposal by a second, independent physician about the same clinical condition (adapted from 1,2 ). Patients are increasingly pursuing second opinions, although precise data on their frequency are lacking. 3 For people who have cancer, the high-stakes nature of diagnosis, prognosis and treatment heightens the significance of the uncertainties that surround these aspects of care. Patients' experience of these uncertainties may be an important element causing patients with cancer to seek second opinions. Indeed, limited evidence thus far suggests that between 5 and 36% of patients in oncology have sought a second opinion. 4 In some settings within oncology, seeking a second opinion has become more a matter of course than an exception, because multiple, medically equivalent treatment options exist. In such situations, patients' values and preferences should be taken into account to arrive at an individualized treatment decision. Ideally, a single health professional would inform patients in such situations about all available treatment options and assist them in arriving at a decision. 5 In some settings, however, health professionals may inform patients only about the option(s) within their field of expertise and encourage second opinion seeking to collect information about other treatments. For example, men who have prostate cancer are frequently expected or encouraged to pursue multiple opinions from different specialists to be fully informed about all available options. [6][7][8] Seeking a second opinion may offer several possible benefits to patients. Psychologically, it can reduce anxiety or increase their sense of control. Medically, it may lead to a more precise diagnosis or better care. [9][10][11] On the other hand, the vast majority of second opinions appear not to benefit patients medically. 10,12,13 Moreover, they may slow down the diagnostic process and be physically and financially demanding for both patients and physicians. 9,11,13 The potential harms and benefits of second opinions have created debate about how desirable these consultations are. 11,14 This debate is impaired by limited insight on people's motivations to seek second opinions, how they evolve and their consequences.
Uncertainty may be a crucial element throughout these different phases of the second opinion process. Uncertainty, defined as a "subjective perception of ignorance", 15 has long been acknowledged as central to medical practice. [15][16][17] Patients' uncertainty may pertain to numerous issues, including the accuracy of their diagnosis, the efficacy of their treatments, their prognosis and the quality of their care. Uncertainty-as experienced by patients, physicians or communicated between physicians and patients-may influence patients' decision to request a second opinion. Moreover, patients' levels of experienced uncertainty may be influenced by the second opinion, and how this uncertainty changes may ultimately affect patients' care experiences and outcomes.
Currently, we lack empirical evidence and in-depth understanding of the role and evolution of uncertainty in second opinions. In this study, this problem was investigated in the prostate cancer setting, where uncertainty is abundant. Clinically localized prostate cancer is an exemplary "preference-based medical condition": none of the available treatment options, that is radiotherapy, surgery and active surveillance, are medically superior in terms of potential benefits and harms for individual patients. 18 Substantial uncertainty also exists regarding the optimal treatments for advanced prostate cancer, that is hormonal, radiation or chemotherapy. Patients with both localized and advanced prostate cancer may seek second opinions to deal with these uncertainties. Other issues of uncertainty may also be important to patients with prostate cancer, but their nature remains to be identified.
The aim for this study was to explore in-depth the evolution of uncertainty in second opinions about prostate cancer, specifically (i) what specific uncertainties influence patients to seek second opinions and (ii) how second opinions may affect patients' sense of uncertainty and subsequent experiences with their care. Findings may contribute to insights about the second opinion process and may yield strategies to help both physicians and patients in communicating about and dealing with uncertainty.

| METHODS
A qualitative study using semi-structured interviews was performed, using the constant comparative method. 19 This method is aimed at generating theory based on the data, rather than conducting analysis based on an existing theoretical framework. 20 Analysis using the constant comparative method begins with open coding (summarizing and categorizing the data), followed gradually by axial coding (confirming codes and examining broader relationships), resulting in the identification of common themes. 21

| Participants and recruitment procedures
Patients with prostate cancer across the disease spectrum (clinically localized through metastatic) who requested a second opinion were purposefully recruited through two channels. First, at Maine Medical Partners-Urology (MMPU), an eight-physician urology practice in Portland, Maine, patients who either visited for a self-initiated second opinion or requested to be referred for a second opinion to a different institution. Second, patients visiting support groups run by the Maine Coalition to Fight Prostate Cancer (MCFPC), a statewide patient support and advocacy organization, were invited to participate if they had self-requested a second opinion in the past 2 years. Furthermore, patients were included of various ages, socio-economic backgrounds and types of second opinions (diagnostic and therapeutic), to capture variation in these characteristics with regard to uncertainty experience. Participants were rewarded a $50 gift card incentive. The Maine Medical Center Institutional Review Board exempted the study from review.
Eligible patients were informed about the study face-to-face or by telephone by either a patient navigator (MMPU) or by a support group moderator (MCFPC). Potential participants provided verbal initial consent to be contacted. The researcher next contacted patients by phone, providing additional information about the study, answering questions, requesting definitive consent and scheduling the interview.
Recruitment and data acquisition stopped when three consecutive interviews did not yield any new information.

| Data collection
In-depth, semi-structured telephone interviews were conducted and audio-recorded by an experienced interviewer (MH) with a background in psychology. The interview protocol is displayed in Table 1, and evolved primarily around motivations and experiences of the second opinion, and the experience of uncertainty in the second opinion process. Throughout the interview, any expressions related to experiencing or communicating about uncertainty were explored in-depth.

| Analysis
All interviews were transcribed verbatim and analysed using MAXQDA12, 22 following guidelines for qualitative research. 23 During data acquisition, three interviews were read in-depth and discussed by three authors (MH, CG and PH; with backgrounds in psychology, public health, and medicine and bioethics, respectively) to allow revising of the protocol. Second, these authors independently coded and jointly discussed three other interviews to arrive at an initial coding scheme. Subsequently, two authors (CG and MH) coded all interviews independently. Codings were compared and discussed after each three consecutive interviews, with a third author (PH) present. The coding scheme was revised continuously, based on outcomes of the analysis. Initial codes were grouped per theme and then hierarchically organized. Throughout the analysis, all authors kept notes of broader themes emerging from the data. Finally, common themes related to second opinions and uncertainty were derived from clustering of the data. A fourth author (ES; background in psychology) critically reviewed general themes identified in the analysis.

| RESULTS
Of the 34 patients approached for participation, 10 declined or could not participate, because they could not be reached (n=9), or felt uncomfortable with an interview (n=1). Data of one other participant were disregarded because of insufficient technical quality of the audio-recording. Patients' mean age was 65 years (range 52-73).
Thirteen patients had early-stage prostate cancer, of whom six had not yet chosen a treatment option. Of the nine patients with advanced prostate cancer, six were currently receiving some form of treatment and one had not yet received any treatment. Seven patients (30%) had high school or some college, 11 (48%) had a college degree, two (9%) had a graduate degree, and three (13%) had a PhD or postgraduate degree. All patients were US-born.
Patients' most salient uncertainties contributing to their wish for a second opinion were [1] uncertainty about the information receiveddue to suboptimal timing, perceived bias or perceived insufficiency (par. 3.1.1); [2] uncertainty about how to integrate the informationdue to lack of guidance or need for decision support (par. 3.1.2); and [3] uncertainty about the physician's alignment with the patient's perspective-due to unshared uncertainty (par. 3

| Uncertainty about when, how and how much information is provided
Patients reported several ways in which their need for information was not properly addressed, causing uncertainty and leading them to seek second opinions (Table 2). First, suboptimal timing-when information was provided-caused uncertainty: newly diagnosed patients reported feeling overwhelmed at the time of diagnosis, when many urologists immediately started talking about treatment options. Several patients reported this was too early for them, as they were still processing their cancer diagnosis, which caused high levels of uncertainty about their life and future. This suboptimal timing led to uncertainty about the meaning of information and how to use it, as illustrated in Q1 and Q2 (Table 2).
Seeking a second opinion was a means for some patients to acquire more time to process the information and make a decision, as illustrated in Q3.   A second issue causing uncertainty was how the information was delivered: patients perceived the information they received to be insufficient, biased or otherwise unreliable (see Q4). Patients reported feeling that the information they received was specifically incomplete because it was biased towards the physician's own specialty (eg surgery for the urologist, radiotherapy for the radiation oncologist), thereby exacerbating therapeutic uncertainty, as illustrated in Q5.

Reduction in uncertainty
Some patients reported seeking second opinions to be provided with a fuller picture of the treatment options and hence reduce their uncertainty (Q6 and Q7).
A third issue was how much information was provided. Some patients acknowledged having high information needs, as illustrated in Q8. For these men, uncertainty arose because their needs were not being met in their first consultation. To arrive at a sense of certainty, these men often sought multiple opinions. A few patients referred to this as "buying more certainty" and felt privileged to have the funds and connections to access a greater number of highly expert physicians (Q9 and Q10).

| Uncertainty about how to integrate the information
Other patients felt fully informed, but still experienced uncertainty about how to synthesize and use the information to come to the right treatment decision. The experienced lack of guidance caused distress, decisional uncertainty and feelings of abandonment as illustrated in Q11-Q13 (Table 2). Patients with decisional uncertainty sought second opinions to reduce their uncertainty or acquire more neutral treatment advice (Q15). Yet although many patients perceived the lack of decisional support as negative, others reported feeling comfortable about making an individual decision (Q14). to maintain a sense of hope. If their physicians did not acknowledge this need for uncertainty, they would similarly seek a second opinion (Q18).

| Uncertainty about the physician's alignment with the patient's perspective
Other patients, however, did not share the uncertainty expressed by their physician due, for example, to a high need for prognostic certainty that their physician could not provide (Q19).
Similarly, some patients acknowledged preferring the most "reassuring" opinion that best met their need for certainty about treatment options (Q20).

Reduction in uncertainty No reduction or increase in uncertainty
Uncertainty about physician's alignment with patient's perspective T A B L E 2 (Continued)

| Effects of second opinions on patients' uncertainty
Seeking second opinions had variable effects on patients' uncertainty.
Although it reduced uncertainty for many patients, others reported that their uncertainties remained or even increased. The extent to which patients' level of uncertainty was affected by the second opinion depended on how patients' information needs or desire for decisional guidance was addressed, or the degree to which the physician providing the second opinion shared their level of uncertainty (see Table 2).

| Meeting patients' need for information
In many cases, patients' information needs were better met in the second opinion, which reduced their uncertainty. For some, the later timing of the second opinion helped them to be better prepared and, resultantly, better able to comprehend the information provided (see for example Table 2

| Providing decision support
For some patients, decisional uncertainty was reduced as a result of the second opinion. These patients reported experiencing a greater sense of collaborative engagement in their second opinion: not only did they perceive the physicians to be more neutral and bias-free, but they also felt the physicians collaborated with them in making a treatment decision, as illustrated in Q27.
Conversely, some patients' decisional uncertainty was not reduced. They felt that, despite seeking more than one opinion, they did not receive sufficient guidance to make a decision (Q28).

| Sharing patients' level of (un)certainty
To some patients, the perception that the physician performing the second opinion shared their uncertainty had a beneficial effect. One patient, for example, felt uncertain about the treatment option of active surveillance, but was reassured by the acknowledgement of this uncertainty by the physician performing the second opinion (Q29).
Another patient expressed a need for uncertainty about the effectiveness of alternative or future treatments to retain hope and felt that an acknowledgement of this uncertainty by his physicians would allow him to maintain a positive attitude (Q31). Conversely, for others, the need to maintain uncertainty was not met by the second opinion. For example, one patient sought a second opinion to maintain a sense of uncertainty and hope about possible treatments, but found that this hope was not confirmed by the oncologist providing the second opinion (Q30).

| Adequacy of information
Uncertainty was frequently the result of patients' perception that the information they received was incomplete or biased. They used the second opinion to obtain a better overview or validation of the initial doctor's recommendation. Patients' information needs ranged widely: some expressed high needs and were comfortable acquiring as much information as possible, whereas others were not comfortable with too much information and felt overwhelmed by it. Patients may have different coping styles in managing threatening information. Low information seekers do not actively seek information or even avoid being confronted with it. 24 High information seekers may actively aim to reduce their anxiety by seeking more information, even though that information may in some cases yield even more uncertainty. 25 Patients with high information needs in the present study expressed the belief that second opinions should be routinely obtained. Some patients appeared to have more resources to actually satisfy their high information needs, which allowed them to "buy more certainty"-as second opinions can sometimes be costly-by obtaining more information from different sources. This is an important avenue for future research, as it suggests that people with lesser financial resources but high information needs might be forced to tolerate more uncertainty than people with greater resources-potentially exacerbating health disparities.
Proper timing of the information may be crucial to prevent patients from feeling uncertain and overwhelmed in processing the highly complex information provided to them directly after diagnosis. Indeed, several patients in the present study reported seeking a second opinion to buy more time to get in the right state of mind to process all the information. This suggests that the need for second opinions might be lessened if physicians could more proactively assess patients' degree of emotional distress following disclosure of the cancer diagnosis, and adjust the timing and amount of subsequent information accordingly.

| Adequacy of decisional support
The results further suggest that even when patients receive suffi-

| Unshared uncertainty
The findings on patients' need to feel a shared level of uncertainty with their physicians may be an extension of Epstein & Street's notion of the "shared mind" 33

| Recommendations
The recent increase in patient-initiated second opinions increases financial burden on the health-care system. 13 The present results additionally show that because of their potentially diverse effects on patients' well-being, they should be used judiciously. Second opinions may be a useful tool for some but not all patients, and they should not be viewed as a solution to current limitations in the organization of care. Some sources of patients' uncertainty could be addressed within the initial consultation, obviating the need for a second opinion. However, our results suggest that some care delivery processes are better than others in meeting patients' needs for certainty and uncertainty. For example, offering a multidisciplinary team-based approach to guide patients through the treatment decision may be better than having patients independently visit multiple specialists.
Clinicians need to be trained in SDM to enable them to share decisional responsibility with patients, instead of delegating it completely, and to assess patients' preferred involvement in decision making.
Both clinicians and patients could also benefit from existing tools to promote decision making, such as question prompt sheets or other decision aids. 38,39 Both multidisciplinary collaboration and enhanced SDM may result in a significant reduction in uncertainty experienced by patients. Similarly, it may be better to tailor the timing of treatment discussions to individual patients' preferences and abilities, rather to treat all patients in the same manner. These care processes, however, may be challenging to implement and require substantial changes in the organization of prostate cancer care.
Yet some of the problems that motivate patients to seek second opinions may not be addressable in any other way. Even with optimal information provision, uncertainties will always remain not only in prostate cancer care, but health care in general. 40 Some of these uncertainties might be reducible, and this possibility-as well as the inherent challenge in determining the extent to which any given uncertainty is reducible-will motivate people to seek second opinions. These possibilities arguably justify the provision of second opinions by the healthcare system. And yet many uncertainties in health care are irreducible, and both patients and physicians must ultimately reach a point at which they must stop seeking more information. 35 At this point, the challenging task for physicians is to focus less on information per se and more on how to assist patients in managing irreducible uncertainty. The problem of second opinions in oncology care thus ultimately comes down to the problem of helping people tolerate uncertainty. 15 Determining exactly how to address this problem is the critical future challenge.