Systematic Review: Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer

University of Minnesota School of Medicine, Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, Minneapolis, Minnesota 55417, USA.
Annals of internal medicine (Impact Factor: 17.81). 03/2008; 148(6):435-48.
Source: PubMed


The comparative effectiveness of localized prostate cancer treatments is largely unknown.
To compare the effectiveness and harms of treatments for localized prostate cancer.
MEDLINE (through September 2007), the Cochrane Library (through Issue 3, 2007), and the Cochrane Review Group in Prostate Diseases and Urologic Malignancies registry (through November 2007).
Randomized, controlled trials (RCTs) published in any language and observational studies published in English that evaluated treatments and reported clinical or biochemical outcomes in localized prostate cancer.
2 researchers extracted information on study design, sample characteristics, interventions, and outcomes.
18 RCTs and 473 observational studies met inclusion criteria. One [one randomized controlled trial] [corrected] RCT enrolled mostly men without prostate-specific antigen (PSA)-detected disease and reported that, compared with watchful waiting, radical prostatectomy reduced crude [corrected] all-cause mortality (24% vs. 30%; P = 0.04) and prostate cancer-specific mortality (10% [corrected] vs. 15% [corrected]; P = 0.01) at 10 years [corrected] Effectiveness was limited to men younger than age 65 years but was not associated with Gleason score or baseline PSA level. An older, smaller trial found no significant overall survival differences between radical prostatectomy and watchful waiting (risk difference, 0% [95% CI, -19% to 18%]). Radical prostatectomy reduced disease recurrence at 5 years compared with external-beam radiation therapy in 1 small, older trial (14% vs. 39%; risk difference, 21%; P = 0.04). No external-beam radiation regimen was superior to another in reducing mortality. No randomized trials evaluated primary androgen deprivation. Androgen deprivation used adjuvant to radical prostatectomy did not improve biochemical progression compared with radical prostatectomy alone (risk difference, 0% [CI, -7% to 7%]). No randomized trial evaluated brachytherapy, cryotherapy, robotic radical prostatectomy, or photon-beam or intensity-modulated radiation therapy. Observational studies showed wide and overlapping effectiveness estimates within and between treatments. Adverse event definitions and severity varied widely. The Prostate Cancer Outcomes Study reported that urinary leakage (> or =1 event/d) was more common with radical prostatectomy (35%) than with radiation therapy (12%) or androgen deprivation (11%). Bowel urgency occurred more often with radiation (3%) or androgen deprivation (3%) than with radical prostatectomy (1%). Erectile dysfunction occurred frequently after all treatments (radical prostatectomy, 58%; radiation therapy, 43%; androgen deprivation, 86%). A higher risk score incorporating histologic grade, PSA level, and tumor stage was associated with increased risk for disease progression or recurrence regardless of treatment.
Only 3 randomized trials compared effectiveness between primary treatments. No trial enrolled patients with prostate cancer primarily detected with PSA testing.
Assessment of the comparative effectiveness and harms of localized prostate cancer treatments is difficult because of limitations in the evidence.

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    • "Many of these patients nevertheless undergo surgery, radiation , or other aggressive treatments associated with chronic— and substantial—side effects [3] [4] [5]. Active surveillance, which entails careful monitoring of selected patients with early stage prostate cancer and treatment of those who demonstrate evidence of disease progression, provides a viable and safe alternative to immediate treatment [6] [7] [8]. "
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    ABSTRACT: Background: Diet may substantially alter prostate cancer initiation and progression. However, large-scale clinical trials of diet modification have yet to be performed for prostate cancer. The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) is investigating the effect of increased vegetable consumption on clinical progression in men with localized prostate cancer. Study design: MEAL is a randomized, phase III clinical trial designed to test whether an intervention that increases vegetable intake will decrease the incidence of clinical progression in men with clinically localized prostate cancer on active surveillance. We are randomizing 464 patients to either a validated telephone-based diet counseling intervention or a control condition in which patients receive a published diet guideline. The intervention will continue for two years. The primary outcome variable is clinical progression defined by serum prostate-specific antigen (PSA) and pathological findings on follow-up prostate biopsy. Secondary outcome variables include incidence of surgical and non-surgical treatments for prostate cancer, prostate-cancer related patient anxiety and health-related quality of life. Conclusion: The MEAL Study is assessing the effectiveness of a high-vegetable diet intervention for preventing clinical progression in men with localized prostate cancer on active surveillance.
    Contemporary Clinical Trials 05/2014; 38(2). DOI:10.1016/j.cct.2014.05.002 · 1.94 Impact Factor
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    • "We did not include all possible treatment options in our model. There is no conclusive comparative evidence available for alternative treatment options such as brachytherapy or intensity modulated radiation therapy [20,62]. Finally, we assumed that surgical treatment of benign prostate syndrome under AS did not affect the probability of disease progression, which might not be realistic. "
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    ABSTRACT: There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of [euro sign]6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of [euro sign]96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS, utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients' valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences.
    BMC Health Services Research 04/2014; 14(1):163. DOI:10.1186/1472-6963-14-163 · 1.71 Impact Factor
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    • "Radical whole gland surgery or radiation therapy can result in substantial side effects. Urinary incontinence (5%–20%), erectile dysfunction (30%–50%), and bowel toxicity (5%–10%) are typical complications of radical treatment [3,4]. For the treatment of low-risk PCa, active surveillance (AS) can be a treatment option; however cancer-related anxiety is the major drawback to this course [5]. "
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    ABSTRACT: A major limitation of performing hemiablative focal therapy (FT) for prostate cancer (PCa) is the possibility of accompanying significant cancer in the contralateral side of the prostate that is missed on prostate biopsy. We attempted to verify whether clinical and biopsy-related parameters can be used to predict the absence of significant cancer in the prostate lobe. We assumed that hemiablative FT could be performed in patients with low-risk PCa, with unilateral tumors as assessed by transrectal ultrasound-guided biopsy. We evaluated 214 patients who had undergone radical prostatectomy (RP) and fulfilled the eligibility criteria. Seemingly preserved lobes, defined by the absence of cancer on biopsy, were classified as lobes with no cancer (LNC), lobes with insignificant cancer (LIC), and lobes with significant cancer (LSC) according to RP pathology. Cases with an estimated tumor volume of <0.5 mL, a Gleason score of <7, and organ confinement without Gleason pattern 4 were classified as LIC. Univariate and multivariate logistic regression analyses were performed to identify predictors for LSC. Predictive accuracies of the multivariate models were assessed using receiver operating characteristic curve-derived areas under the curve. Of 214 evaluated lobes, 45 (21.0%), 62, (29.0%), and 107 (50.0%) were classified as LNC, LIC, and LSC, respectively. Among the clinical and biopsy-related parameters, prostate-specific antigen density and prostate volume were identified as significant predictors for LSC in univariate regression analysis. However, multivariate analysis did not identify an independent predictor. Predictive accuracies of the multivariate models did not exceed 70.4%. Conventional parameters have limited value in predicting LSC in patients who are candidates for hemiablative FT.
    03/2014; 2(1):37-42. DOI:10.12954/PI.13031
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