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Making the "Right Choice": Considerations Regarding Treatment-Related Regret in Localized Prostate Cancer

By: Christopher J. D. Wallis, MD, PhD, FRCSC; Zachary Klaassen, MD, MSc; Daniel Barocas, MD, MPH | Posted on: 01 May 2022

Patients newly diagnosed with prostate cancer or considering active treatment following a period of active surveillance have a number of guideline-recommended treatment options.1 Assisting patients with navigating these treatment decisions, through the process of shared decision making, is a key role of any physician who treats patients with prostate cancer. Ultimately, while we may consider a number of factors when counseling patients including oncologic outcome, the burden and cost of treatment, immediate treatment-related toxicity and longer-term urinary, bowel and sexual side effects and others, the ultimate goal ought to be to assist patients in choosing the treatment option that is most consistent with their goals and preferences. Conversely, patient-reported regret regarding their treatment choice ought to reflect the opposite of our desired outcome. In our view, treatment-related regret provides an integrative, patient-centered outcome measure, which accounts for the treatment-related morbidity, oncologic outcomes, psychosocial burdens and costs associated with prostate cancer diagnosis and treatment. Further, these outcomes are contextualized through a patient’s own lens, weighing their relative importance and utilizing a comparative, counterfactual framework. The experience of regret depends on a comparison between a decision (ie the chosen treatment) and its alternatives.

Table. Pairwise association between treatment modality and patient-reported regret at 5 years after diagnosis among patients with localized prostate cancer

D’Amico Risk Category Treatment Comparison OR (95% CI)* p Value OR (95% Cl)† p Value
All Surgery vs active surveillance 2.40 (1.44–4.01) <0.001 1.73 (0.99–3.02) 0.05
Radiotherapy vs active surveillance 1.53 (0.88–2.66) 0.13 1.42 (0.77–2.59) 0.26
Surgery vs radiotherapy 1.57 (1.11–2.22) 0.01 1.22 (0.82–1.83) 0.33
Low risk Surgery vs active surveillance 2.73 (1.45–5.14) 0.002 2.08 (1.05–4.13) 0.04
Radiotherapy vs active surveillance 1.82 (0.90–3.68) 0.10 1.69 (0.79–3.62) 0.18
Surgery vs radiotherapy 1.50 (0.90–2.47) 0.11 1.24 (0.70–2.17) 0.46
Intermediate risk Surgery vs active surveillance 2.26 (0.85–6.05) 0.10 1.51 (0.51–4.43) 0.46
Radiotherapy vs active surveillance 1.56 (0.56–4.32) 0.39 1.42 (0.47–4.35) 0.54
Surgery vs radiotherapy 1.45 (0.91–2.32) 0.12 1.06 (0.62–1.80) 0.83
High risk Surgery vs active surveillance 0.51 (0.09–2.99) 0.45 0.27 (0.04–1.81) 0.18
Radiotherapy vs active surveillance 0.19 (0.03–1.27) 0.09 0.12 (0.02–0.92) 0.04
Surgery vs radiotherapy 2.64 (1.12–6.25) 0.03 2.22 (0.86–5.77) 0.10

*Multivariable models accounted for baseline characteristics, including age at diagnosis, participatory decision-making tool score, educational level, comorbidity (Total Illness Burden Index), race and ethnicity, receipt of androgen deprivation therapy within 1 year, receipt of pelvic radiotherapy and registry site.

Adjusted for baseline characteristics and longitudinal functional outcomes, including patient-reported domains of the 26-item Expanded Prostate Index Composite and 36-Item Short Form Health Survey consisting of urinary incontinence, urinary irritation/obstruction, sexual dysfunction, bowel dysfunction, hormonal symptoms, physical function, mental function, and energy and fatigue.

Model further adjusted for D’Amico risk category.

Recently, we used the prospective population-based Comparative Effectiveness Analysis of Surgery And Radiation (CEASAR) cohort to assess rates and predictors of patient-reported treatment regret among men deciding on treatment for localized prostate cancer.2 Importantly, we found that treatment-related regret was experienced by 13% (95% CI 12%–15%) of patients at 3 and 5 years following diagnosis. This means that more than 1 in 8 patients feels like they made the wrong treatment choice.

“In our view, treatment-related regret provides an integrative, patient-centered outcome measure, which accounts for the treatment-related morbidity, oncologic outcomes, psychosocial burdens and costs associated with prostate cancer diagnosis and treatment.”

We explored a number of important patient, disease and treatment factors which may contribute to regret. We found that the strongest predictor of regret, as may be expected given its counterfactual nature,3,4 was pre-treatment expectations and the degree to which they were met. Thus, regret was more common among patients who judged that their treatment effectiveness (71% [95% CI 55%–87%] vs 13% [95% CI 11%–14%]) and treatment side effects (48% [95% CI 41%–55%] vs 10% [95% CI 8%–11%]) were “a lot worse” than expected. This effect remained strong, even after adjustment for baseline demographics, clinicopathological characteristics, treatment modality and longitudinal assessments of patient-reported functional outcomes with a significantly higher likelihood of regret among patients reporting that treatment effectiveness (aOR 5.28, 95% CI 2.12–13.19) and treatment toxicity/side effects (aOR 5.74, 95% CI 3.91–8.43) were worse than expected.

We further found that active intervention (particularly with radical prostatectomy) compared to active surveillance was associated with an increased likelihood of regret: regret was reported by 16% (95% CI 14%–18%) of patients undergoing surgery, 11% (95% CI 9%–14%) of patients undergoing radiotherapy and 7% (95% CI 4%–11%) of patients undergoing active surveillance. This effect was particularly strong among patients with low-risk disease. Conversely, among patients with high-risk disease those who opted for active surveillance (rather than active treatment with surgery or radiotherapy) were more likely to report regret, even after accounting for differences in patient-reported functional outcomes such as urinary incontinence and erectile dysfunction (see table). Among patient-reported functional outcomes, only declines in sexual function were significantly associated with regret.

These findings suggest that the pre-treatment counseling process, and better aligning patients’ treatment expectations with physician-anticipated treatment outcomes may be key to improving the important, patient-centric outcome of regret. While ongoing work to improve outcomes from prostate cancer treatment are important, efforts aimed at improving the pre-treatment counseling process and supporting patient decision making may be more effective at reducing regret. While decision aids have been examined in this context with the hope that they may reduce decisional conflict,5 the recent Alliance A191402CD trial showed that these did not improve prostate cancer knowledge6 and thus may not be as effective at aligning expectations and anticipated outcomes as hoped. Importantly, Holmes and colleagues showed that a “discussion of all treatment options” was associated with a lower likelihood of treatment-related regret (12.1% vs 18.1%, adjusted odds ratio 0.59, 95% CI 0.37-0.95).7 In our view, this may be best accomplished with multidisciplinary consultation. Additionally, given low rates of cancer attributable mortality and these findings, widespread use of active surveillance where appropriate would be expected to decrease treatment-related regret.

“These findings suggest that the pre-treatment counseling process, and better aligning patients’ treatment expectations with physician-anticipated treatment outcomes may be key to improving the important, patient-centric outcome of regret.”

We believe that more thorough, evidence-based counseling, with a particular focus on patient values and priorities, prior to treatment may reduce regret and ameliorate the associated mental health outcomes.8,9 Treatment preparedness, focusing on expectations and on treatment toxicity, delivered in the context of shared decision making, requires further study to examine whether it can reduce regret.

  1. National Comprehensive Cancer Network: NCCN Clinical Practice Guideslines in Oncology: Prostate Cancer, version 1.2019. Plymouth Meeting, Pennsylvania: National Comprehensive Cancer Network 2019.
  2. Wallis CJD, Zhao Z, Huang LC et al: Association of treatment modality, functional outcomes, and baseline characteristics with treatment-related regret among men with localized prostate cancer. JAMA Oncol 2022; 8: 50.
  3. Huang WH and Zeelenberg M: Investor regret: the role of expectation in comparing what is to what might have been. Judgm Decis Mak 2012; 7: 441.
  4. Zeelenberg M, van Dijk WW, Manstead ASR et al: On bad decisions and disconfirmed expectancies: the psychology of regret and disappointment. Cogn Emot 2000; 14: 521.
  5. Riikonen JM, Guyatt GH, Kilpelainen TP et al: Decision aids for prostate cancer screening choice: a systematic review and meta-analysis. JAMA Int Med 2019; 179: 1072.
  6. Tilburt JC, Zahrieh D, Pacyna JE et al: Decision aids for localized prostate cancer in diverse minority men: primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD). Cancer 2022; 128: 1242.
  7. Holmes JA, Bensen JT, Mohler JL et al: Quality of care received and patient-reported regret in prostate cancer: analysis of a population-based prospective cohort. Cancer 2017; 123: 138.
  8. Hu JC, Kwan L, Saigal CS et al: Regret in men treated for localized prostate cancer. J Urol 2003; 169: 2279.
  9. Hurwitz LM, Cullen J, Kim DJ et al: Longitudinal regret after treatment for low- and intermediate-risk prostate cancer. Cancer 2017; 123: 4252.

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