Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer

Abstract

Background:Men diagnosed with localised prostate cancer (LPC) face difficult choices between treatment options that can cause persistent problems with sexual, urinary and bowel function. Controlled trial evidence about the survival benefits of the full range of treatment alternatives is limited, and patients' views on the survival gains that might justify these problems have not been quantified.Methods:A discrete choice experiment (DCE) was administered in a random subsample (n=357, stratified by treatment) of a population-based sample (n=1381) of men, recurrence-free 3 years after diagnosis of LPC, and 65 age-matched controls (without prostate cancer). Survival gains needed to justify persistent problems were estimated by substituting side effect and survival parameters from the DCE into an equation for compensating variation (adapted from welfare economics).Results:Median (2.5, 97.5 centiles) survival benefits needed to justify severe erectile dysfunction and severe loss of libido were 4.0 (3.4, 4.6) and 5.0 (4.9, 5.2) months. These problems were common, particularly after androgen deprivation therapy (ADT): 40 and 41% overall (n=1381) and 88 and 78% in the ADT group (n=33). Urinary leakage (most prevalent after radical prostatectomy (n=839, mild 41%, severe 18%)) needed 4.2 (4.1, 4.3) and 27.7 (26.9, 28.5) months survival benefit, respectively. Mild bowel problems (most prevalent (30%) after external beam radiotherapy (n=106)) needed 6.2 (6.1, 6.4) months survival benefit.Conclusion:Emerging evidence about survival benefits can be assessed against these patient-based benchmarks. Considerable variation in trade-offs among individuals underlines the need to inform patients of long-term consequences and incorporate patient preferences into treatment decisions.

Patient-reported outcomes of cancer survivors in England 1–5 years after diagnosis: a cross-sectional survey

“…Similarly, among colorectal survivors, nearly a quarter reported urinary leakage and 19% reported difficulty in controlling their bowels. These rates are comparable to other studies of cancer patients,32 but exceed those seen in non-cancer populations where the prevalence of urinary incontinence in adult men was 4.5% overall, rising to 16 for over 75-year-olds 33. In this study, the presence of ‘urinary leakage’ in prostate survivors and ‘of difficulty controlling their bowels’ in colorectal survivors were significantly associated with lower QoL scores making such symptoms important to address.…”

Factors associated with current and severe physical side-effects after prostate cancer treatment: What men report

“…Little is known about other physical effects, such as hot flushes and fatigue, and their associated factors. Moreover, although, men are more likely to make decisions about treatment based on the possibility of severe, rather than milder side-effects (King et al, 2012), little is known about what factors are associated with either higher or lower risk of experiencing severe side-effects.…”

“…In addition, 75% of men reported at least one 'current' physical symptom (Gavin et al, 2015). The most common side-effects after PCa treatment are sexual dysfunction (in particular erectile dysfunction and libido loss) urinary incontinence, and bowel problems (Miller et al, 2005, King et al, 2012, Darwish-Yassine et al, 2014, Potosky et al, 2004.…”

“…While randomised controlled trials of treatment have been conducted, and there is little strong evidence that any of the treatment yield survival benefits over the other (King et al, 2012, Wagner et al, 2011, Heidenreich et al, 2008, Wilt and Ahmed, 2013. PCa treatment decisions are based on the consultation between the patient and the physician, aiming to find the best fit to the patient's personal and clinical characteristics (e.g.…”

Informed prostate cancer risk‐adjusted testing: a new paradigm

“…There has been increasing uptake of PSA testing and attendant risks of over‐diagnosis and over treatment present clinical and ethical dilemmas . If treated, men are at risk of adverse treatment‐related effects and a contestable survival benefit.…”