“A disconnect between patient expectations and outcomes” is a major contributor to treatment-related regret among patients with localized prostate cancer, according to a study published in JAMA Oncology.¹

The encouraging news is that “given its link to pretreatment expectations,” as the study authors noted, “treatment-related regret may be more modifiable”—through improved counseling and identifying patients’ values and priorities—than functional outcomes and other factors impacting the survivorship experience of patients with prostate cancer. “These data emphasize the opportunity to improve patients’ experience and outcomes in prostate cancer with better alignment of our expected outcomes with their expectations,” the study’s lead author, Christopher J.D. Wallis, MD, PhD, said in an interview with The ASCO Post. Dr. Wallis is a urologic oncologist at Mount Sinai Hospital in Toronto and Assistant Professor, Division of Urology, University of Toronto.

Study Details

The population-based, prospective cohort study relied on data from 2,072 men who had been recruited for the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation for Localized Prostate Cancer) study from five Surveillance, Epidemiology, and End Results (SEER)–based registries in the CEASAR cohort. Men included in this recent analysis were 80 years of age or younger at diagnosis, had clinically localized prostate cancer (cT1–cT2, cN0, cM0), had a prostate-specific antigen level less than 50 ng/mL, and were enrolled within 6 months of diagnosis. The median age at diagnosis was 64. Most men (76%) identified as White; 12%, as Black; 7%, as Hispanic; and 3%, as Asian.

“This analysis is restricted to those who primarily received radiotherapy, surgery, or active surveillance, because they are the predominant and guideline-recommended treatments,” the authors noted. A slight majority of patients, 55%, underwent surgery, and 32% underwent radiotherapy, which “reflects the general pattern in the United States: surgery is more commonly used than radiation approaches,” Dr. Wallis said. Patients who had radiotherapy tended to be older, had greater comorbidity, and had slightly higher-risk disease than those undergoing surgery, which also fits the general pattern. “Many studies have borne that out,” Dr. Wallis noted.

“Patients undergoing active surveillance, although older than those undergoing surgery, were younger than those undergoing radiotherapy and were more likely to have low-risk disease,” the researchers reported. The authors acknowledged that “many patients with low-risk disease in the CEASAR study received an active intervention, which, although common at the time, does not reflect current practice patterns favoring surveillance.”

“The rates of active surveillance in patients with low-risk disease have increased over time, and so active treatment rates have correspondingly gone down,” Dr. Wallis explained.

Some Degree of Regret

Patients completed mail surveys at baseline, 6 and 12 months, and 3 and 5 years after diagnosis. Survey results were supplemented with information abstracted from medical records. The authors found no “meaningful difference” between rates of treatment-related regret at 3 and 5 years.

Questions designed to assess treatment-related regret include the following: “I would be better off with a different treatment,” “I feel the treatment was the wrong one,” “I would choose another treatment if I could,” and “I wish I could change my mind about the treatment I chose.” The most likely to “express some degree of regret” were patients who had surgery, and the least likely, were those under active surveillance.

Overall, 13% of patients reported treatment-related regret at 5 years. This included 6% of patients undergoing surgery, 11% undergoing radiotherapy, and 7% undergoing active surveillance. There was no apparent association between regret and race. “Consistent with previous studies, we found that regret was less common among older men,” the authors reported.

“We didn’t specifically ask the question why they developed treatment-related regret,” Dr. Wallis added. “But, in general, we postulate that patients who received treatment are more likely to have regret as a result of the toxicity of treatment, whereas, for patients who did not have treatment and developed regret, it is more likely to be because of the idea of a missed window for treatment and disease progressing.”

Risk Assessment

“Risk assessment, using criteria from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), D’Amico risk classification, or the American Urological Association, is a standard approach that all clinicians would use to guide their treatment recommendations,” Dr. Wallis stated.

In this study, findings were modified after stratifying by D’Amico risk category. “Among patients with low- and intermediate-risk disease, active treatment was associated with a higher likelihood of regret compared with active surveillance,” the authors wrote. “Whereas this effect was reversed among those with high-risk disease, this association was not always statistically significant on pairwise testing. Comparisons between surgery and radiotherapy consistently showed higher regret with surgery, although they differed significantly only among those with high-risk disease.”

“Overall, 13% of patients reported treatment-related regret at 5 years.”

— Christopher J.D. Wallis, MD, PhD

“It comes down to the trade-off that all prostate cancer treatment entails, which is disease control and treatment toxicity,” Dr. Wallis explained. “In the case of low-risk prostate cancer, the risk of disease progression and oncologic harm is quite low. As a result, we have a high bar to make sure our treatments are not morbid.” Conversely, “when disease risk is higher and cancer progression is more likely, patients are more likely to regret not pursuing aggressive therapy with its associated side effects, because they are more likely to have disease progression.”

Sexual Dysfunction

Sexual dysfunction, but not other patient-reported functional outcomes, was significantly associated with regret among patients who chose surgery or radiotherapy. Although patients who opt for either treatment may develop erectile dysfunction, it tends to occur sooner among patients treated with surgery and later with radiotherapy.

“Urinary incontinence among surgical patients is much less common than erectile dysfunction. However, it also may carry a large burden for some patients and may contribute to their regret,” Dr. Wallis commented.

Working on 10-Year Follow-up

“We are actively working on a 10-year follow-up with this cohort. It will assess many outcomes, including the main analysis of the CEASAR cohort, looking at patient-reported functional outcomes, such as incontinence, erectile dysfunction, and bowel function,” Dr. Wallis said.

“We are also going to look at chart evaluations for rates of second therapies, biochemical recurrence, and other treatments. We will look at treatment-related regret as well. Regret is an important metric, and we need to consider our patients’ priorities,” Dr. Wallis said. Knowing about patients’ treatment-related regrets may help reduce the likelihood of such regrets in similar patients moving forward. “We want to do better for them,” he added.

DISCLOSURE: Dr. Wallis has received personal fees from Janssen Canada outside this study.

Treatment regret is an important metric that is really premised on this negative cognitive-based emotional feeling. And it’s premised really when we consider it on a counterfactual comparison, i.e. what is the alternative result that someone may have received if they made a different decision in the past? And as a result, it is influenced by pre-decision expectations. In our view, treatment regret is a really good outcome measure, because it integrates the effects of treatment-related functional impairments, oncologic outcomes and associated anxiety, as well as behavior, emotional, and interpersonal changes that may be associated with the prostate cancer diagnosis and treatment. And all of these are considered through the lens of an individual patient’s values and expectations.

And so our hypotheses in this study were that treatment modality would be independently associated with the likelihood of treatment regret, that this association would be mediated by the functional outcomes achieved following treatment, and that decision making style and expectations initially will influence the long-term risks of developing regret. And so to assess this, we relied upon the CEASAR cohort, which is a prospective population-based cohort of patients accrued from five population-based SEER registries, who were diagnosed with localized prostate cancer during 2011. Patients could be included if they were aged less than 80 years in clinically localized disease, PSA less than 50, and were enrolled within 6 months of their diagnoses. Patients completed surveys at baseline, 6 months, 12 months, 3 years, and 5 years after enrollment.

In this study, we focused on the regret measure as an outcome. This was developed and validated by Dr. Clark, and using his approach, we define significant regret as scores of 40 or greater and assess these at 3 and 5 years following enrollment. This highlights the conceptual framework through which we considered our analyses. Looking at treatment regret as the outcome on the far right, we can see that a baseline patient characteristics influence their pretreat and expectations, and these may be mediated through the decision-making style. And these characteristics, along with their tumor and disease characteristics, may influence the treatment modality selected. In turn, treatment modality influences functional outcomes. And together, both expectations, treatment modality, functional status, as well as the mediating effect of social support, may lead to treatment regret.

And so we considered a number of important exposures. In terms of primary treatment modality, we compared surgery to radiotherapy and surveillance. Now, we further considered patient-reported functional outcomes, as measured used in the EPIC-26 and the SF-36 to assess prostate cancer-specific and overall functional status. Finally, we added important demographic and baseline characteristics, including the decision-making style, measured using a PDM, or a participated decision-making, 7 tool, as well as the difference between expectation and outcomes, both in terms of oncologic efficacy and toxicity. And then we considered social supports, age, race, ethnicity, education level, and marital status that’s potentially important in influencing a man’s likelihood of developing treatment-related.

To analyze this, we built three successive logistic progression models. The first assessed treatment modality and adjusted for D’Amico risk group, age, education, comorbidity, race or ethnicity, ADT, use of pelvic radiotherapy, study site, and decision-making style. Model two added in treatment-related health problems, patient-reported functional outcomes, perceptions of treatment efficacy and toxicity, and social support. Model three added marital status, baseline social support, and baseline functional outcomes to the first model. As we know, D’Amico risk group may influence treatment decisions. We further stratified the models according to these criteria. I’m now going to hand it over to Zach to walk us through the results of this analysis.

Zachary Klaassen: Thanks, Chris. You can see this is the diagram of assembly of the CEASAR study court and final analytical cohort, and over a number of exclusion criteria. The analytical cohort, for this specific study looking at treatment regret, was 2072 patients, including 1136 that underwent surgery, 667 that underwent radiation, and 269 that underwent active surveillance.

This is the table 1 looking at baseline characteristics of these patients, and I’ve broken this down into two slides given the size of the table 1. We can see here on the far right as the p-value followed by all the patients together, and then sequentially active surveillance, radiation, and surgery. So looking at some of these highlights of the variables, we can see here that, not surprisingly, patients that underwent surgery were a little bit younger. We can see that the most common race was white patients at three-quarters in each of these groups. There’s a pretty balanced division of patients based on educational level across these three groups. And we can see that nearly 80% of patients were married at the time of their enrollment.

In terms of D’Amico risk category, the majority of patients in each of these groups was low or intermediate risk, and we can see that the baseline PSA was 5 to 6 for each of these patients. Looking at the most common PSA level at the time of diagnosis, most common was 4 to 10 in 60-70% of patients, the most common clinical tumor stage was T1, ranging from 7485% of patients, and the majority of patients had a biopsy Gleason Score of 6 or 3+4. Subsequently, any ADT within 1 year was only seen in primarily the radiation cohort, at 32%. To conclude the baseline characteristics, we can see that this is the breakdown by site, and with a high proportion of patients either being in Los Angeles or in the Louisiana cohort.

This table looks at the pairwise association between treatment modality and patient regret at 5 years after diagnosis. And so what’s important in this table is, at the left here, this is D’Amico risk category among all patients and then stratified by D’Amico risk individually, and to the right of this is the treatment comparison adjusted for basically patient demographics. And we can see, on the far right, this is adjusted for demographics as well as patient long-term functional outcomes.

Going back to the starred or the asterisks for the statistically significant differences, we see that surgery versus active surveillance was associated with treatment regret, with an odds ratio of 2.40. And this odds ratio decreased to 1.73, 95% confidence interval of 0.99 to 3.02 after adjusting for patient long-term outcomes. Looking at surgery versus radiotherapy, we see here a statistically significant odds ratio for regret of 1.57. However, this is nullified after adjusting for the patient long-term outcomes. In low-risk patients, we see significant regret for surgery versus active surveillance, with an odds ratio of 2.73, which was still significant after adjustment for long-term outcomes of the odds ratio of 2.08. Moving down to the high-risk D’Amico group, we see you that radiotherapy versus active surveillance was actually protective for regret, even after adjusting for long-term functional outcomes, with an odds ratio of 0.12. And we see that for high-risk patients surgery versus radiotherapy, odds ratio of 2.64. But when we adjust for patient long-term outcomes, this becomes non-significant.

This looks at the adjusted odds ratios for treatment-related regret, and you can see here that the ability of using a decision tool was associated with less regret. Sexual function was also associated with less regret. And we moved down to treatment here, surgery versus active surveil. This was associated with regret, with an odds ratio of 2.08. And then if we look at the increasing level of education level compared to lower levels of education, this was associated with less treatment-related regret. Not surprisingly, development of health problems due to prostate cancer treatment at 6 months, as well as perception of treatment effectiveness compared with expectations at 5 years, as well as perception of treatment of adverse events compared with expectations at 5 years, all were significantly associated with more treatment regret with significant odds ratios, as listed here.

This is the baseline characteristics associated with patient-reported regret at 5 years, we can see here that increasing age, the utilization of a decision tool, as well as social support were all protective for treatment related regret. As we see here in the D’Amico risk category, high-risk patients with an odds ratio of 1.5 was also associated with treatment-related regret.

This Bland-Altman plot looks at the scores at 3 and 5 years. The goal of this analysis was to see if we assessed outcomes of 3 years, if they differed from 5 years. And the summary from this figure is that, generally, the regret scores were consistent over time, regardless of when we analyzed the data.

Several discussion points from this study. This is the first study in men with localized prostate cancer to find higher rates of regret among those who were actively treated, either with radical prostatectomy or radiotherapy, compared to those on surveillance after adjusting for baseline differences. This was modified by D’Amico risk categories. We saw that low and intermediate risk patients that had active treatment were more associated with likelihood of regret compared to active surveillance, with the reverse effect noted in patients with high-risk disease. Comparisons between surgery and radiotherapy showed higher regret with surgery. However, this differed significantly only in the patients with high-risk disease. So a disconnect between patient expectations and treatment outcomes for both efficacy and toxicity contributes more substantially to regret than patient-reported outcomes, treatment modality, or clinical pathological features, and thus, treatment-related regret may be more modifiable than other contributors to the survivorship experience of these patients, given its link to pretreatment expectations.

So in conclusion, these findings suggest that more than 1 in 10 patients with localized prostate cancer experience treatment-related regret. There’s a disconnect between patient expectations and outcomes that appears to drive treatment-related regret to a greater extent than disease, characteristics, treatment modality, or patient reported functional outcomes. And finally, improve counseling at the time of diagnosis and before treatment, including the identification of patient values and priorities, may decrease regret among these patients. We thank you for your attention. We hope we enjoy this UroToday Journal Club discussion.

Source : ascopost.com