Financial Toxicity Among Patients with Metastatic Prostate Cancer: A Mixed Methods Approach to Identify Effective Interventions

Abstract

Purpose:

Financial toxicity associated with treatments for metastatic prostate cancer remains poorly defined. We sought to understand aspects of financial toxicity not captured in a commonly employed financial toxicity questionnaire and identify potential interventions to help alleviate financial toxicity through a convergent mixed methods approach.

Materials and Methods:

Patients seen at our institution’s advanced prostate cancer clinic were approached for completion of the Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire (quantitative analysis). A maximal variation purposive sample was chosen to participate in focus group discussions (qualitative analysis). Conventional content analysis was performed using an inductive approach. COST-FACIT scores were compared between patients experiencing high and low financial toxicity using Wilcoxon rank sum test.

Results:

Three themes were identified through qualitative analysis: workload, coping strategies, and communication. We found alignment with the existing theory of financial capacity across our findings. Two unique aspects of financial toxicity emerged which were not assessed quantitatively and deemed to be significant. Specifically, cost transparency (including healthcare teams knowledgeable about and willing to discuss costs) and inclusion of informal caregivers in financial toxicity screening and decision-making may guide future interventions aimed at limiting financial toxicity in this population.

Conclusion:

Prolonged treatment courses involving multiple lines of treatment with varying costs result in distinct financial toxicity components for patients with metastatic prostate cancer that are not assessed with COST-FACIT. Improving cost transparency, healthcare team knowledge and engagement, and providing resources to support informal caregivers may have a significant impact on the financial toxicity experienced by these patients.

Introduction

Treatment costs are a particular concern for cancer patients, with up to 64% reporting stress and worry about paying their cancer-related medical bills.^{1, 2} Perhaps not surprisingly, patients with higher out-of-pocket costs have been found to have worse treatment adherence.^{3, 4} Such compromises may in part explain observed associations between financial distress and quality of life as well as increased mortality.⁵

Financial toxicity (FT), a term that is used to describe unintended harm to patients caused by the cost of cancer care, is increasingly recognized as an important patient-centered outcome measure. While various reported findings regarding FT may be generalizable,⁶ FT specific to metastatic prostate cancer (mPCa) is largely unknown. Importantly, mPCa represents a disease state for which the number of distinct and combinations of systemic therapies is rapidly expanding. In addition, there is increasing interest in multimodal treatment regimens, including the addition of surgery and/or radiotherapy to systemic agents.^{7, 8} This rapid expansion of management strategies has been coupled with equally rapid increasing costs.⁹

Currently, there are insufficient data to suggest that existing FT measures accurately describe the experience of patients with mPCa.¹⁰ Previously, we described the prevalence and severity of FT and common coping mechanisms among patients in our institution’s mPCa clinic.¹¹ Herein, we sought to expand on these findings by understanding what areas of FT (if any) are not adequately assessed through current measures, and to use patient experiences and preferences to inform interventions which may attenuate FT.

Materials and Methods

Following Institutional Review Board approval, all patients in the mPCa clinic at our institution were approached between February and April, 2022 for completion of the Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire.¹² The details of survey content and administration have been previously dsescribed.¹¹ A maximum variation purposive sample of individuals experiencing both extremes of FT (defined as a score > 24 for low FT and ≤ 24 for high FT) was obtained for subsequent focus group inclusion. Eligible patients were contacted by phone and those willing to be included provided written informed consent. Baseline patient characteristics were obtained using a combination of patient-reported data and review of electronic medical records. English speaking patients who were being treated for mPCa were eligible. Patients with additional non-prostate malignancies or with non-metastatic prostate cancer were excluded.

Data Integration

Integration of the quantitative and qualitative findings was achieved using a convergent mixed methods design (Figure 1).¹³ Investigations were conducted using a pragmatist philosophical paradigm.¹⁴

Figure 1:

Data Integration schema.

COST-FACIT: Comprehensive Score for Financial Toxicity

Qualitative Methods

Thematic saturation was achieved following completion of six focus groups (three involving patients with high FT and three involving patients with low FT) within 1 year of enrollment, each lasting 90 minutes, and comprising of six to ten participants.

Focus group sessions were conducted using video conferencing software and were led by a single moderator (KB) who is trained and skilled in qualitative methodology. Open-ended scripted questions were asked using a moderator’s guide (Supplemental Material).

A hierarchical coding system was developed and refined using the focus group moderator guide and a preliminary review of the transcripts (Supplemental Material). Transcripts, quotations, and codes were managed using Microsoft Excel 2016 and SPSS version 28.0.

Quantitative data analysis

Scores for each COST-FACIT item were compared between patients with high and low FT using Wilcoxon rank sum test. Responses were summarized using median and interquartile ranges. A two-sided p value of <0.05 was considered statistically significant. All quantitative analyses were performed using BlueSky Statistics version 7.40 (BlueSky Statistics LLC, Chicago, IL).

Theoretical triangulation

We used an iterative inductive/deductive approach to qualitative data analysis.^16–18 Inductively, we sorted the quotes by coding category and used the sorted quotes to identify higher order themes and relationships between themes. Deductively, we were guided by the existing theory of financial capacity. Financial capacity was defined by Espinoza Suaraz et al. as “a patient’s ability to afford and address their healthcare costs.”¹⁹ Three conceptual models were used to inform and contextualize financial capacity: the theory of patient capacity (TPC),²⁰ the Cumulative Complexity Model (CCM),²¹ and the Burden of Treatment Theory (BTT).²² Further descriptions of these models are provided in the Supplemental Material. The process was iterative in that the analysis was theoretically informed, while specific themes and subthemes were derived from the coded qualitative data.

Results

Overall, 94 patients were approached for both quantitative and qualitative study. Of these, 35 ultimately agreed to participate in qualitative analysis (18 with low FT and 17 with high FT) and are included here. Patient demographics are provided in Table 1.

Table 1:

Patient Characteristics

Characteristics	Low Financial Toxicity (N=18)	High Financial Toxicity (N=17)	Total (N=35)	p value
Age (years) - median (IQR)	73 (69, 75)	67 (64, 69)	69 (66, 74)	0.01
Race - n (%)
Black or African American	0 (0%)	1 (5.9%)	1 (2.9%)
White	17 (94.4%)	16 (94.1%)	33 (94.3%)
Other	1 (5.6%)	0 (0%)	1 (2.9%)
Marital status - n (%)				0.1
Single, never married	0 (0%)	2 (11.8%)	2 (5.9%)
Married	17 (100.0%)	13 (76.5%)	30 (88.2%)
Divorced	0 (0%)	2 (11.8%)	2 (5.9%)
Household size - median (IQR)	2 (2, 2)	2 (2, 2)	2 (2, 2)	0.4
Employment status - n (%)				0.7
Employed full-time (≥36 hours per week)	2 (11.1%)	3 (17.6%)	5 (14.3%)
Employed part-time (<36 hours per week)	1 (5.6%)	2 (11.8%)	3 (8.6%)
Self-employed	1 (5.6%)	0 (0%)	1 (2.9%)
Retired	14 (77.8%)	11 (64.7%)	25 (71.4%)
Not working outside the home	0 (0%)	1 (5.9%)	1 (2.9%)
Annual Household Income - n (%)				0.01
<~20,000	0 (0%)	1 (6.2%)	1 (2.9%)
~20,000 to 39,999	0 (0%)	3 (18.8%)	3 (8.8%)
~40,000 to 59,999	2 (11.1%)	3 (18.8%)	5 (14.7%)
~60,000 to 79,999	5 (27.8%)	1 (6.2%)	6 (17.6%)
~80,000 to 99,999	2 (11.1%)	6 (37.5%)	8 (23.5%)
~100,000 or more	9 (50.0%)	2 (12.5%)	11 (32.4%)
Education - n (%)				0.4
High school graduate	0 (0%)	1 (5.9%)	1 (2.9%)
Some college	2 (11.1%)	4 (23.5%)	6 (17.1%)
Finished 4-year college	7 (38.9%)	3 (17.6%)	10 (28.6%)
At least some graduate school	9 (50.0%)	9 (52.9%)	18 (51.4%)
Insurance type - n (%)				0.4
Private Insurance + Medicare	14 (77.8%)	10 (58.8%)	24 (68.6%)
Private Insurance only	1 (5.6%)	4 (23.5%)	5 (14.3%)
Medicare Advantage	3 (16.7%)	3 (17.6%)	6 (17.1%)
Distance traveled - n (%)				0.8
<20 miles	2 (11.8%)	1 (5.9%)	3 (8.8%)
20–40 miles	0 (0%)	0 (0%)	0 (0%)
41–120 miles	4 (23.5%)	6 (35.3%)	10 (29.4%)
>120 miles	11 (64.7%)	10 (58.8%)	21 (61.8%)
Site of metastases - n (%)				0.6
Bone only	3 (17.6%)	1 (5.9%)	4 (11.8%)
Bone + Lymph nodes	7 (41.2%)	9 (52.9%)	16 (47.1%)
Bone + Visceral	4 (23.5%)	2 (11.8%)	6 (17.6%)
Lymph nodes only	3 (17.6%)	5 (29.4%)	8 (23.5%)
PSA at study enrollment - median (IQR)	0.1 (0, 2.5)	1.0 (0, 9.9)	0.3 (0, 4.0)	0.2

IQR: interquartile range

Three overarching thematic categories were identified through qualitative analysis: (1) “workload”; (2) “coping strategies”; and (3) “communication”. Each item of the quantitative survey was categorized within these major themes and subthemes (Table 2). Of note, “communication” did not match with a COST-FACIT item, and so quantitative data are not displayed for this theme.

Table 2:

Joint display of quantitative and qualitative findings.

Theme	Comparative COST-FACIT responses between those with low and high financial toxicity (quantitative findings)				Representative Quotes (qualitative findings)
1. Workload
1.1 Direct Costs	COST-FACIT Item #4: I feel I have no choice about the amount of money I spend on care.*				1.1.1 But I would say, as a cost of involvement in cancer treatment, one of those costs is the anxiety level of trying to make sure that you′ve covered all your bases. Have you purchased the right insurance? Do you have coverage where you need it? Is the drug covered…and so, as a cost of this disease, that′s one of them, is that anxiety of trying to make sure that you have actually figured it out, what was needed, because there′s lots of holes that you can drop into if you′re not paying attention. 1.1.2 I have in my hand, the drugs that were delivered today, [olaparib], and it′s $16,000 a month, which if you calculate that, is $192,000 a year. Yeah, I have a drug coverage, but it′s a tier five drug, and the long and the shore of it is it would cost me $8,000 a year out of the pocket…they′ve been able to get me a grant to pick up the $8,000, but it′s income based, and thank God the income is $91,000 and under, so I do qualify, thank goodness. 1.1.3 …the impact has been there and certainly the deductible and out-of-pocket maximum were unexpected expenses, but I happened to be in a position where I was able to keep up with those and get those paid off relatively quickly. And also, I was able to work for the first three and a half months of my diagnosis, so that didn′t cause a significant decrease in my income and the short-term disability provided, I believe 66% of my discretionary income. I basically get 66% of my paycheck every two weeks. With long-term disability, it goes down to 50%, but that′s still workable, between my income and my wife′s income. It hasn′t put us in the kind of dire straits that I know so many people can experience with healthcare costs, particularly for something like cancer. 1.1.4 Oh, when they said [leuprolide acetate] shots are $3,000 an injection, is one. I′m not on Medicare yet, I′m 63, so I still have insurance coverage, so when you get those bills to the point, it′s like, “Well, shit, do I open this one and see what the lottery ticket says? Do I owe, or is it still covered?” But you still have a large deductible, and once you burn through that it′s still cost, but you deal with it, I guess. 1.1.5 But this last one here that I′m on here with [enzalutamide], I had to use a combination of about three different directions, to be able to actually not have any cost with it, and I′ve only been on it two and a half months, but what′s really scary to me right now is [lutetium], okay? I desperately want to get started with that treatment, and I meet all the qualifications to get started with the treatment and everything, except I wake up every morning, wondering, “Is Medicare going to reject that? And if so, are we talking about six...” There′s six treatments every six weeks, is what′s been shared with me, and are we talking about $20,000 a treatment or are we talking about $200,000 a treatment? 1.1.6 The costs are significant, but I guess we have the money to pay for it…I′m not going to spend all my money to get three more months. At some point I would just fold, to be honest with you, but I′m at the beginning of my journey.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.0 (1.0, 4.0)	1.0 (0, 1.0)	0.002
	COST-FACIT Item #7: I am able to meet my monthly expenses.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	4.0 (3.3, 4.0)	3.0 (3.0, 3.0)	< 0.001
1.2 Indirect Costs	COST-FACIT Item #5: I am frustrated that I cannot work or contribute as much as I usually do.*				1.2.1 I transitioned from commercial insurance to Medicare drug coverage, and I spent untold hours talking to many, many people within the company, and within Medicare and so on, just trying to get the assurance that this one drug was going to be covered at all. 1.2.2. I worked for the first couple of months, and the job that I had, if I wasn′t there, someone else had to cover for me, and I was old enough to retire. I was 62, so I turned in my retirement and actually retired so I could go…every three weeks and have chemo. And I did that for a while. The financial, as far as the medical, has not been terrible, but we do live about 600 miles away, and the travel and accommodations to stay and that sort of thing, that′s been the main financial challenge that we′ve had. 1.2.3 So I sold my business, which is helpful with having that money in the bank, but basically that was before retirement, before we could get on social security or anything. So, my wife ended up working for longer than she really would′ve had to, but I couldn′t really work. It was difficult for me to work at that time, so it′s impacted us that way. 1.2.4 For us, when we started at first…the transportation was an issue. That was a two-day drive up there and a two-day drive back. And to do that every three months, it was getting very expensive. So, what we did and what it caused us to do was to move. We moved up here…and so instead of two days…now we′re three hours…and this is where my family′s from too. So, there are other benefits as well, but that move, that traveling was a major expense and moving was a major expense as you might expect, but it′s a lot more cost-effective now. 1.2.5 Yes. I guess the most side effect I′ve had is, and I still don′t know what is the cause of it, but since I had chemo and radiation, I have developed a strong intolerance of dairy products and eggs, all of which I love, and that′s been a real headache. So I got to eat non-dairy stuff. It′s expensive. It doesn′t taste like the real thing, but what can you do? 1.2.6 What big concern I have is with the IRS. We itemize our taxes because we′ve got enough things to itemize, and our medical bills. I don′t think the IRS is doing a good job for us, because they let us write off 17 cents a mile, and the business deduction was something like 57 cents a mile. And when you stayed in a hotel, according to my accountant, they gave you $50 a night for the hotel. I think that′s ridiculous. Plus, you have to have a threshold before you can even start writing off medical expenses, and that′s $7,500 in out-of-pocket or adjusted gross income. And if you′re over 65, it′s 7.5%. If you′re under 65, it′s 10%. 1.2.7 For me, there′s one that′s actually coming up. I′m going to have to be getting my radiation in Rochester, which is 90 minutes away from me, and I′ll have to go every day for Monday through Friday for five weeks. And it′s not realistic to do a three-hour round trip drive every day.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	4.0 (3.0, 4.0)	1.0 (1.0, 2.0)	< 0.001
	COST-FACIT Item #9: I am concerned about keeping my job and income, including work at home.*
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	4.0 (4.0, 4.0)	2.0 (0, 3.3)	< 0.001
2. Coping Strategies
2.1 Psychosocial	Quality of Life:				2.1.1 I′m glad to hear that I′m done now with chemo, but I hope we don′t have to do that over again…I′m only 70. I still farm, I still work, but doggone it, I do notice the energy is...I hope when this fall comes, I got more energy than I got now. And I will. You got to have a positive attitude or otherwise you′re sunk from the beginning. So, it′s all good. You just got to work through the bumps. 2.1.2 It financially impacted me when my prostate cancer started coming back and I went through the eight weeks radiation. After I did that, I decided... I had a natural resource consulting company. We did a lot of natural resource forestry and pre-preservation work with golf courses and developments, things for pre-preservation, and natural resource inventories and things. And I had decided to just sell the business. I just lost…I lose that desire to think so far ahead and just start to think about the present. 2.1.3 Between the surgery, it was fine then, still working, but then between the radiation and the cryosurgeries, it pretty much destroyed everything so I′m totally incontinent…I do have some scar tissue now with the past cryosurgeries, which is causing me problems sitting and driving a car, and then it swells up. I just have problems with that. But it′s just a constant. And the financial thing comes in there when you start to go from [leuprolide acetate], which is covered, to [apalutamide] which is covered, but it′s like $7,000 a month on my insurance. All these things just, they keep adding up. 2.1.4 Sure. We′re trying to maintain a certain quality of life. All of us here probably think the same way. And for me, if I have a plan and then we can populate the gaps between the medical appointments, I find that to be somewhat satisfying. As somebody said earlier, you′re somewhat confined. It might be a big corral, but you can′t leave the corral. For me, though, it′s just trying to plot out what the future′s going to be or what we know that we think the future′s going to be and try to fit in the rest of your life into those pockets.
	COST-FACIT Item #8: I feel financially stressed.*
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	4.0 (4.0, 4.0)	1.0 (0.8, 2.0)	< 0.001
	COST-FACIT Item #10: My cancer or treatment has reduced my satisfaction with my present financial situation.*
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	4.0 (3.3, 4.0)	1.0 (0, 2.0)	< 0.001
	COST-FACIT Item #12: My illness has been a financial hardship to my family and me.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	0 (0, 1.0)	3.0 (2.0, 4.0)	< 0.001
	Uncertainty:				2.1.5 And for me, it came up with the haggling that goes on with the insurance company. So the [enzalutamide], I believe it′s called...is a very expensive injection that I have to have as part of my chemotherapy...And it actually got to the point where my oncologist actually had to call in and have an appointment with someone higher up in the insurance company to explain, "No, this person actually needs this and we don′t have any other options." And so, in that case, I had already met my out-of-pocket maximum, but that′s where I first started hearing about the expense of it. And then it comes up, there′s that anxiety and uncertainty of, is this going to be covered or not? 2.1.6 In some of the cases, the claims that go through it may take the insurance company six weeks to finally process them. And then lo and behold, you get a letter that this isn′t covered and then you have to appeal. And yeah, there′s a lot of administrative details that in my experience, I′ve had to deal with quite a bit of that. 2.1.7 Don′t get me wrong, but I don′t think people realize what these numbers [costs] are out here. I think that it would be nice to know more about them in advance because I don′t know the day that when, God forbid, I missed a payment and I didn′t know it, and lo and behold, they canceled my policy and don′t want to pay any of the claims. It′s certainly possible. I hate to say it. 2.1.8. The issue comes down to... You may start here with the treatment and then they turn around and decide that this isn′t working, or it would be a better idea to go in a different direction. Then you need another cost estimate and so on. I think that you have to break these things down into the various different series of these expenses that may come up. I think it would be a great thing for people to understand what it costs. I remember, when I had my radiation treatments, I was blessed with the thought that I didn′t have to come up with much money for them, but then I got the EOB from Medicare, and low and behold, I didn′t realize that it was over a hundred grand. 2.1.9 The first thing I do, and I belong to, like I said, a forum that is sort of exclusive to stage four prostate cancer patients. I′ll just tell everybody; it′s called Health Unlocked. It′s an excellent site and forum, and as these new treatments come available in clinical trials, et cetera, I follow the randomized clinical trials, what stages they′re in, and once they′re approved by FDA. So, the [lutetium, Lu 177 vipivotide tetraxetan], for example, the first thing I looked up is... Although I′m not eligible for it, you have to be castrate resistant to be eligible for that treatment. But I looked up, the first thing I looked at, knowing I was going to be in Medicare′s system, is Medicare going to cover it? 2.1.10 It′s a process. I had this egg dumped in my lap, and so I went out to find out how much was it with my insurance company? I paid for it. How much was it with GoodRx? Where were the options? What were the options that were available? Depending upon your situation, there are options.
	COST-FACIT Item #2: My out-of-pocket medical expenses are more than I thought they would be.*
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.5 (2.0, 4.0)	2.0 (0, 2.0)	0.005
	COST-FACIT Item #3: I worry about the financial problems I will have in the future as a result of my illness or treatment.*
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.0 (2.0, 4.0)	1.0 (0, 1.0)	< 0.001
	COST-FACIT Item #11: I feel in control of my financial situation.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.5 (3.0, 4.0)	2.0 (1.0, 2.0)	< 0.001
2.2 Financial	COST-FACIT Item #1: I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment.				2.2.1 …for some reason, I wasn′t eligible for any of these assistance program from the manufacturers. Maybe because I have a Medicare Part D program. I′m not exactly sure the reason why I wasn′t eligible in their minds for assistance. And that [apalutamide] is very expensive. The list price was about $10,000 a month. Then they decided to raise it in January to like $13,000 a month. 2.2.2 I′m a veteran, and I applied to the VA for drug costs, but it was income based and I didn′t qualify for anything. I didn′t go to Vietnam, so I wasn′t disabled or exposed to any Agent Orange, but they wouldn′t cover one cent for me. 2.2.3 …But one of my concerns there though is, I′ve heard that there is the American Cancer Society has Hope House for people who are going through radiation. And they provide housing for that during that time, I believe at no cost, but there′s a lot of demand for those slots and there may not, depending on exactly when I start, there will have to be some serendipity involved for me to be able to get in from day one and be there for the whole five weeks. And there′s no way of knowing until I start that process. So that′s a big kind of open question, as to how I′m going to manage that. If I have to stay at an extended stay hotel or something for two or three weeks, that will get very expensive, very quickly. 2.2.4 The way they did it is that they used my time, so I was still getting paid as if I was fully working. I was getting my full salary and that helped me out. 2.2.5 Thank God my wife has health insurance. She has an employer that has health insurance that literally carried me the entire time. Then Medicare came along. So now that and health insurance is primary, and the secondary is Medicare. But there′s a cost to do that. So, it costs basically about $7,000 a year just to carry the… Well, the deductibles are 2,800, plus the health insurance of probably $350 a month. So, there′s a real cost. I think with decreased income, not making a professional income and having to do some part-time, I had to kind of balance. And I collected disability at age, when I was going through chemotherapy. 2.2.6 I′m very fortunate that…I was able to just keep sitting down and keep making some phone calls and just keep saying, "Hey, I′m looking for the person that can help me. " Every day I would say the same thing…I tried to engage whoever was willing to help and guide me in the right direction, and I was able to get some assistance from a foundation with one of the medications. And [abiraterone], I was able to get assistance from the manufacturing based off of my income, that was 50% less at retirement than it was when I was still working. 2.2.7 They got me on a program that, that drug doesn′t cost me a dime. Some kind of type of a scholarship, which is really helpful because it′s not a cheap drug. So, as far as getting help…it′s been good. I absolutely can′t complain. They′ve been very, very helpful. They put you in front of the right people, but you still have that out-of-pocket expense that is burdensome.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.0 (2.0, 4.0)	2.0 (0, 2.0)	0.002
	COST-FACIT Item #6: I am satisfied with my current financial situation.
		Low Financial Toxicity	High Financial Toxicity	p value
	median (IQR)	3.5 (3.0, 4.0)	1.0 (0, 2.0)	< 0.001
3. Communication
3.1 Healthcare Team	Competence:				3.1.1 …I think all the clinics have one individual that looks for money to help you, whether it′s grants or from cancer societies or for the drug companies, and that′s all they do….I think everyone has someone there that that′s all they do. 3.1.2 I think, like I′m hearing from the rest of you, the…system has clearly been the most helpful as far as helping to navigate some of these different costs and things of that nature. They′ve been so much more helpful than anyone else, but in their defense, they don′t know what path each of us is going to take for sure either. They go along and as our situation develops, and this happens and that happens and they make the best recommendation of what they think the treatment is for that situation. And each of us, our body chemistries are different and so forth. So even though our paths have been similar in some ways, in other ways, they′re different.
	Knowledge:				3.1.3 The people that you′re working with have a much better idea than you do of the effect of those drugs on your financial capability, and on your insurance and so on. And my experience, like I mentioned before, I think…has been incredible, because I′m sitting there with the doctor prescribing something, and the nurse is already out ahead of me, saying, "Here′s what we need to do to file a proper form." And so on. And they know about it, I don′t. And I think that′s what a good medical company, practitioner, MD, whatever it is, has been really helpful to me. 3.1.4 I think, it would be very helpful if someone on a team would be able to have that conversation as well. If a person is all completely on their own, as some people must inevitably be to make sure that they′re aware of their options with regards to counseling and being connected to the resources that are available…Having somebody who could maybe prompt that question and get to know the individual and ask those questions and help connect them to resources, I think would be a hugely beneficial thing. 3.1.5 I can give you two levels that I′ve been working with for a long, long time. And one level is here in the [redacted]. In their pharmacy department, they have a financial druggist that remains in contact with the major suppliers of meds. And if you fall into a med that that′s going to be supplied by this pharmacy, they will have already figured out, based on your insurance that they′ve already had, on how much it′s going to cost or not cost, or is it available or not available, no arguments. There′s a pretty clean operation. 3.1.6 If you could get treatment, good treatment, good radiation treatment closer to home, those kind of things would be nice. So, if there was somebody on the team maybe that had a good grasp of that, and maybe was responsible for setting up some of these networks, so that we could get treatment at a reasonable cost and maybe include some of the hidden costs like transportation, like room and board and things like that.
3.2 Cost Conversations					3.2.1 I have three different doctors that I′m dealing with, and the first one, I wish they would′ve sat me down right away and let me know that this is going to be a financial journey. Because the first pills that they gave me and I went to the pharmacy to get them, and I got the bill about knocked me off my [inaudible]. I knew there was no way I could afford the copay every month. There′s just no way. You go to the doctors there, that was in my local area here, they had no help for me whatsoever. We′re just kind of on our own. My wife went out and searched all over and we just really had to dig for any financial help that we could find and fortunately we have found some. 3.2.2 No, no. Nobody told me the cost, nor they seem to know what the cost is, and I′m pretty sure don′t, other than they know it′s expensive. [Apalutamide], for example. There′s a pharmacy benefit manager in the middle of things. It is fairly complicated to determine the cost of drugs. 3.2.3 The first I found out about it was when I got my explanation of benefits and they said, “This is what they paid. This is what it costs. This is what your insurance paid, and this is what you owe."” That was about all I ever got about the cost of the treatment that I was getting. 3.2.4 So I think, part of the ideal conversation is for doctors to be better informed about the realities of it and for the insurance providers themselves to even be better informed about what the laws are, and what it takes to be in line with expectations legally, and for the expectations of the consumer as well. When I try to contract somebody to do something at my house, I get an estimate first. I′d know what the cost is upfront. I′ve never had someone in a medical profession tell me, even begin to tell me. They′re just saying, “Oh, you need this test, you need that test, you need this medication”. But cost has never come into the conversation, ever. And that′s, I think, something that needs to change so that people can make informed decisions. Not only about what they need medically, but what′s appropriate for them and realistic for them financially. 3.2.5 I think it′d be helpful if somebody would′ve handed me a document that said essentially, “We′re proposing this, we have your health insurance information and there are people here that are going to look at that. And if they conclude that you′re not covered and that you′re going to have a large out-of-pocket expense, you′re going to hear from us.” I think that′d be useful. If I could see that on a piece of paper. I will suggest before they would just tell me that, and that that′s good too. But no, if somebody would′ve had a piece of paper and said, we are doing this and in two days if we learned that you′re going to have a big out-of-pocket expense, we will tell you, you′ll know. That would be helpful. If they′re doing that, of course they got to do it too. But a piece of paper that said that would be reassuring to me. 3.2.6 What I would suggest be done is, when you have a new patient come in, prepare a detailed handout for the patient about all these things we′re talking about, about potential availabilities with your drug company, check with your drug company, see if there′s a plan on this, other potential help on that. If you could put a package together and you keep it up, that might be a good idea. 3.2.7 Because there is a point in all of our lives where we are going to say, “What price, life?” I′m not going to leave this world and leave my wife bankrupt, that′s just not going to happen. So, when it becomes a point where we have to start thinking about selling off things and moving in with our children, we′re going to drop that ball. I found out I had cancer, and guys, I′m not joking about this. The physician that performed the surgery, he sat down, he put his cell phone down, he said, “You have stage four prostate cancer, I′m here to answer any questions you have. Go.” That was literally what he said to me. I was in shock, and financial matters at that point aren′t even in your brain. 3.2.8 I don′t think I want my doctors taking care of that, but it would be nice to have somebody on the team that understood the treatment, and also understood insurance and costs and finance, that could talk about that, address that. With the standpoint of, “Here′s some ways you can meet that and here′s some ways we can help you meet that,” and maybe even come up with ways.
3.3. Inclusion of Informal Caregivers					3.3.1 In my circumstance, I′m extremely fortunate that I have a very strong support group. My wife from the first day, for the first second was we′re going to beat this. She had a very strong attitude about it. She′s been very, very patient with me with regards to the irritability. That′s a side effect of some of the hormone therapies and things like that. I′m very fortunate there. I also have a network of friends and family that check on me regularly and that I can talk to about what I′m going through, not just physically, but how I′m feeling about it. I imagine that not everyone is as fortunate as that. In my profession, I have conversations with students when they start their doctoral degrees. I have my preliminary meeting with them where I talk to them about and get to know them. One of the questions I ask them is, who′s supporting you in this adventure that you′re going on, to get a sense of who they have in their corner. 3.3.2 So, what′s useful to caregivers is relief, for them to have somebody to come in on a regular basis to give them a break. And having been a caregiver, that′s what I would say to you. 3.3.3 I don′t want to have my personal situation all strung out, cost us a ton, and then I′m gone and now my family′s left with what? I′d rather be gone quicker and at least have them left with something rather than me having the last five years of my life, no quality of life, and leave my family with nothing. So those are things that people in our situations think about too. The people that we′re going to leave behind. 3.3.4 My cost, we′re on a limited income because we′re both, my wife and I are on Social Security, and the out-of-pocket expense every year is 12,000 plus. That doesn′t count my travel expenses and rooms…or anything like that. So, the cost burden on the family, and thank goodness one of my siblings offered me some money to cover just one of my pills. The copay on it was, at that time, about $4,000. I′m supposed to have that every month. So, the cost and the financial side of it is almost as stressful as having cancer.

^*COST-FACIT (Comprehensive Score for Financial Toxicity) items that are reverse scored so that lower values are associated with higher financial toxicity.

WORKLOAD

“Workload” refers to the tasks and demands on the patient stemming from life and healthcare. Such demands encompass financial implications from treatment and included two subthemes: 1) direct costs, and 2) indirect costs.

Direct costs

Out-of-pocket costs were exacerbated by unfavorable insurance benefit designs and inhibited patients’ ability to obtain treatments (Quotes 1.1.1, 1.1.2). Quantitative items assessing financial stress were dichotomous between those experiencing low and high FT (COST-FACIT item #8 median [IQR] score: 4.0 [4.0, 4.0] vs. 1.0 [0.8, 2.0] for low vs. high FT respectively, Table 2). However, despite being able to handle current financial obligations, patients with low FT expressed concerns that their financial capacity could change (Quote 1.1.5). Finally, patients’ willingness to pay for direct costs appeared to be dependent on their perception of treatment efficacy (Quote 1.1.6), which was not assessed quantitatively.

Indirect costs

Qualitative descriptions were congruent with quantitative items assessing indirect costs of treatment, with many patients describing alterations to work, early retirement, and caregiver lifestyle changes (Quotes 1.2.2, 1.2.3, 1.2.5). Additional indirect costs not evaluated by the quantitative assessment included the opportunity cost of time spent navigating insurance coverage, as well as costs of travel to treatment sites, including gas, commute time, hotel expenses, and even relocating to be closer to care (Quotes 1.2.2, 1.2.4, 1.2.7).

COPING STRATEGIES

“Coping strategies” are resources patients draw on to meet the workload associated with their treatment. These resources were obtained from two domains: 1) psychosocial and 2) financial.

Psychosocial

Health-related quality of life and treatment uncertainty (including costs) influenced patients’ capacity to cope with financial strain emotionally and intellectually. Patients experiencing greater side effects from treatment were more likely to be dissatisfied with their financial situation (COST-FACIT item #10, mean [IQR]: 4.0 [3.3, 4.0] vs. 1.0 [0, 2.0] for low vs. high FT respectively, Quote 2.1.1, Quote 2.1.2, Quote 2.1.3). Furthermore, patients discussed that their willingness to pay for treatments was dependent on the quality of life while on treatment (Quote 2.1.4)

Quantitatively, patients with high FT were found to be more likely to experience costs that were different from what they expected. Two specific aspects of care contributed to this uncertainty: (1) variability and complexity of insurance coverage (Quotes 2.1.5, 2.1.6, 2.1.7), and (2) inability to forecast the number, type, or duration of treatments (Quote 2.1.8). Resources which offset cost uncertainty were helpful for patients to identify the highest value options as well as provide appropriate financial expectations (Quote 2.1.9, 2.1.10).

Financial

The COST-FACIT items querying patients’ ability to identify financial resources to cover treatment costs are limited to personal assets and net worth. While patients expressed concerns over having enough money in their assets to cover costs, they also expressed frustration with their ability to identify and obtain external funding resources such as pharmacy financial assistance programs (Quote 2.2.1), government programs (Quote 2.2.2), and private charitable services (Quote 2.2.3). When utilized, financial assistance from employers (Quote 2.2.4), disability insurance (Quote 2.2.5), and pharmaceutical companies (Quote 2.2.6, 2.2.7) were effective in mitigating harms from costs.

COMMUNICATION

Effective communication between patients, their informal caregivers (i.e. family and friends who provide patient care at home without payment), and healthcare teams, which was influenced by cost knowledge and willingness to engage in cost conversations, improved financial capacity, while omission of these discussions had the opposite effect.

Healthcare Team

Identifying individuals within the healthcare team who specialize in identifying resources to limit treatment costs was the most consistently cited way that patients were able to navigate FT from their treatments (Quote 3.1.1, 3.1.2). Having a healthcare team that was knowledgeable about the financial implications of treatments alleviated anxieties surrounding costs (Quote 3.1.3, 3.1.4). The impact of an informed interdisciplinary team was more profound when the members shared knowledge and collaborated to provide efficient, patient-centered care that accounted for a patient’s financial capacity (Quote 3.1.5). Furthermore, developing networks to facilitate collaboration between tertiary care referral centers and local practices was suggested to help identify treatments associated with both lower direct and indirect costs (Quote 3.1.6).

Cost Conversation

Patients consistently stated that a lack of conversations about cost prior to initiating treatment contributed to FT. Specifically, patients expressed their belief that greater cost transparency would have helped ease anxiety and enhance shared decision-making (Quotes 3.2.1, 3.2.2, 3.2.4, 3.2.5). Current cost conversations lacked sufficient detail (Quote 3.2.3). Improvement in these conversations was considered crucial to be able to make an informed decision (Quote 3.2.4, Quote 3.2.5). Specifically, having these data available prior to physician consultation was ideal (Quote 3.2.6). These aspects of care (with an emphasis on expected FT from treatments) were necessary to help patients plan their lives in alignment with their values and to limit treatment regret (Quote 3.2.7). Even so, patients remain conflicted on who is best suited to initiate these conversations, as many felt that physicians should not be the ones tasked with providing cost transparency, but should maintain knowledge of cost when providing management recommendations (Quote 3.2.8).

Inclusion of Informal Caregivers

Emotional and financial support from family and informal caregivers was critical in coping with FT (Quote 3.3.1). Resources that supported informal caregivers enhanced their ability to encourage positive coping strategies among the patients they cared for (Quote 3.3.2). In addition, how treatment costs impacted the lives of patients’ loved ones was a strong contributor to the degree of financial stress that they experienced (Quotes 3.3.3, 3.3.4).

THEORETICAL ALIGNMENT

A detailed description of the theoretical alignment in our study is provided in the Supplemental Materials. Briefly, we found theoretical alignment across our findings. Direct and indirect costs were identified as contributors to patient workload. Patients drew on psychosocial and financial resources to cope with these demands. Communication concerning cost expectations between patients and healthcare teams that are knowledgeable and competent influenced the degree to which patients harnessed these coping resources. Furthermore, inclusion of informal caregivers in these communications further improved both psychosocial and financial coping capacity (Figure 2).

Figure 2:

Study alignment with the existing theories of patient capacity, burden of treatment, and cumulative complexity highlighting the importance of healthcare team knowledge, competence, cost transparency, and inclusion of informal caregivers on patients’ ability to cope with increasing workload from direct and indirect costs. Green arrows represent factors that enhance the characteristic they point to, while red arrows represent factors that diminish the characteristic they point to.

QOL: quality of life

Discussion

In this convergent mixed methods study, we identified several relevant aspects of FT among patients being treated for mPCa which are not assessed with the COST-FACIT questionnaire. Two actionable suggestions to improve FT were specifically noted: 1) decreasing the uncertainty of cost by creating knowledgeable healthcare teams who are willing and able to routinely engage in cost discussions, and 2) increasing informal caregiver involvement in FT assessments and shared decision-making processes.

Despite recent passage of the Centers for Medicare and Medicaid Services (CMS) Hospital Price Transparency Final Rule requiring hospitals to make their charges publicly available, our findings suggest that patients lack the ability to estimate expected treatment costs. Cost transparency may be uniquely challenging in the management of mPCa, which typically involves multiple lines of prolonged treatment courses and combination therapies. Moreover, novel agents (with variable unforeseen costs) may become available in the middle of a patient’s treatment course. Together, these unknown variables make forecasting overall treatment costs challenging. To limit financial uncertainty, it is necessary that interdisciplinary healthcare teams are apprised of current drug prices and potential costs of newer treatments on the horizon. [add how this has been attempted?]

Interestingly, we also noted that patients remain conflicted about the “who” and “how” of cost-transparency. In particular, participants expressed concern with physicians being solely responsible for weighing treatment costs in management recommendations. At the same time, physicians have also been reluctant to address treatment costs due, in part, to time constraints and lack of knowledge.^{23, 24, 25} Nevertheless, engaging in these discussions has been shown to reduce out-of-pocket costs without sacrificing quality of oncologic care.²⁶ Our findings suggest that achieving effective cost communication likely demands engagement from multiple healthcare team members who are knowledgeable about the unique impact of costs and who are able to access resources that help limit the negative effects of these costs. This type of assistance appeared to be most needed when discussing oral cancer drugs, which were consistently referenced as a primary source of high treatment costs and major obstacle to obtaining accurate price transparency. Various resources have been evaluated in the literature including online pharmacy drug plan search engines, on-site financial navigators, and financial toxicity tumor boards.^{28, 29} However, efficacy of these resources is varied, and widespread implementation has yet to occur.

Another theme which emerged from our analyses was the importance of engaging informal caregivers in cost discussions. Informal caregivers are an important resource frequently relied upon for financial assistance. These individuals also facilitate patients’ ability to enhance social functioning, which in turn increases capacity.²⁰ Thus, limiting screening efforts and interventions to the patient alone are insufficient; rather, caregivers must also be considered. These findings are consistent with studies detailing the need for additional financial and emotional support services for informal caregivers.³⁰ One proposed solution to identifying informal caregivers at risk for FT is to administer the COST-FACIT questionnaire to these individuals as well as to patients.³¹ Further work is needed to understand how best to incorporate caregivers into decision-making and to expand support services that facilitate their ability to improve patients’ financial capacity.

We recognize that our study is subject to several limitations. Patients included here were predominantly white and seen at a single quaternary care referral center; as such, the generalizability of our findings to other healthcare settings is uncertain. Furthermore, we purposefully chose patients experiencing extremes of FT for our analyses. While this approach helped identify important facilitators and obstacles to financial capacity, it limited our ability to understand the experience of patients experiencing less severe degrees of FT. Nevertheless, this represents what is to our knowledge the first mixed methods evaluation of FT among patients with mPCa and provides unique, hypothesis-generating findings which can inform interventions aimed at improving FT in these patients.

Conclusions

The rapidly evolving treatment landscape for mPCa contributes to a distinct FT among these patients. Moreover, current measures fail to capture the unique components of FT which these patients experience. We utilized a mixed methods study design and provided hypothesis-generating data aimed to inform interventions to improve FT associated with mPCa treatments. Improving price transparency through engagement of a knowledgeable healthcare team and including informal caregivers in cost discussions and FT screening represent examples of opportunities identified which may improve the severity of FT that patients with mPCa experience.