Screening for prostate cancer in the US? Reduce the harms and keep the benefit

While the benefit of prostate‐specific antigen (PSA) based screening is uncertain, a significant proportion of screen‐detected cases is overdiagnosed. In order to make screening worthwhile, it is necessary to find policies that minimize overdiagnosis, without significantly increasing prostate cancer mortality (PCM). Using a microsimulation model (MISCAN) we project the outcomes of 83 screening policies in the US population, with different start and stop ages, screening frequencies, strategies where the PSA value changes the screening frequency, and strategies in which the PSA threshold (PSAt) increases with age. In the basecase strategy, yearly screening 50–74 with a PSAt of 3, the lifetime risk of PCM and overdiagnosis equals, respectively, 2.4 and 3.8%. The policies that reduce overdiagnosis the most (for maximum PCM increases relative to basecase of 1%, 3%, and 5%, respectively) are with a PSAt of 3, (1) yearly screening 50–74 where, if PSA <1 at age 65 or older, frequency becomes 4 years, with 3.6% (5.9% reduction), (2) 2‐year screening 50–72, with 2.9% (24.3% reduction), and (3) yearly screening 50–70 (PSAt of 4 after age 66), with 2.2% (43.4% reduction). Stopping screening at age 70 is a reasonable way to reduce the harms and keep the benefit. Decreasing the stopping age has a larger effect on overdiagnosis reduction than reducing the screen frequency. Screening policies where the frequency of screening depends on PSA result or in which the PSAt changes with age did not substantially improve the balance of harms and benefits relative to simple yearly screening.     

Active surveillance for prostate cancer compared with immediate treatment: an economic analysis

BACKGROUND:

The costs associated with a contemporary active surveillance strategy compared with immediate treatment for prostate cancer are not well characterized. The purpose of this study is to elucidate the health care costs of an active surveillance paradigm for prostate cancer.

METHODS:

A theoretical cohort of 120,000 men selecting active surveillance for prostate cancer was created. The number of men remaining on active surveillance and those exiting to each of 5 treatments over 5 years were simulated in a Markov model. Estimated total costs after 5 years of active surveillance with subsequent delayed treatment were compared with immediate treatment. Sensitivity analyses were performed to test the effect of various surveillance strategies and attrition rates. Additional analyses to include 10 years of follow‐up were performed.

RESULTS:

The average simulated cost of treatment for 120,000 men initiating active surveillance with 5 years of follow‐up and subsequent delayed treatment resulted in per patient cost savings of $16,042 (95% confidence interval [CI], $16,039‐$16,046) relative to initial curative treatment. This represents a $1.9 billion dollar savings to the cohort. The strict costs of active surveillance exceeded those of brachytherapy in the ninth year of follow‐up. A yearly biopsy within the active surveillance cohort increased costs by 22%, compared with every other year biopsy. At 10 years of follow‐up, active surveillance still resulted in a cost benefit; however, the savings were reduced by 38% to $9944 (95% CI, $9941‐$9948) per patient relative to initial treatment.

CONCLUSIONS:

These data demonstrate that active surveillance represents a considerable cost savings over immediate treatment for prostate cancer in a theoretical cohort after 5 and 10 years of follow‐up. Cancer 2012;3512–3518. © 2011 American Cancer Society.     

The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate‐specific Antigen‐era

Widespread prostate‐specific antigen (PSA) screening detects many cancers that would have otherwise gone undiagnosed. To estimate the prevalence of unsuspected prostate cancer, we reviewed 19 studies of prostate cancer discovered at autopsy among 6,024 men. Among men aged 70–79, tumor was found in 36% of Caucasians and 51% of African‐Americans. This enormous prevalence, coupled with the high sensitivity of PSA screening, has led to the marked increase in the apparent incidence of prostate cancer. The impact of PSA screening on clinical practice is well‐recognized, but its effect on epidemiologic research is less appreciated. Before screening, a larger proportion of incident prostate cancers had lethal potential and were diagnosed at advanced stage. However, in the PSA era, overall incident prostate cancer mainly is indolent disease, and often reflects the propensity to be screened and biopsied. Studies must therefore focus on cancers with lethal potential, and include long follow‐up to accommodate the lead time induced by screening. Moreover, risk factor patterns differ markedly for potentially lethal and indolent disease, suggesting separate etiologies and distinct disease entities. Studies of total incident or indolent prostate cancer are of limited clinical utility, and the main focus of research should be on prostate cancers of lethal potential.     

Potential overtreatment among men aged 80 years and older with localized prostate cancer in Japan

Despite treatment guidelines recommending observation for men with low‐risk prostate cancer with life expectancy <10 years, a majority of elderly patients choose active treatment, which may result in overtreatment. Given the growing burden of prostate cancer among men aged ≥80 years (super‐elderly men), accumulation of survival data for evaluation of overtreatment among super‐elderly patients is imperative. Here, we report results of a population‐based cohort study to clarify potential overtreatment of super‐elderly men with localized prostate cancer. We used cancer registry data from the Monitoring of Cancer Incidence in Japan project, which covers 47% of the Japanese population. The subjects were men diagnosed with prostate cancer between 2006 and 2008. Follow‐up period was 5 years. We calculated 5‐year relative survival rates among the active treatment and observation groups after imputation for missing values. Of the 48 782 patients with prostate cancer included in the analysis, 15.1% were super‐elderly men. The 5‐year relative survival rates of super‐elderly men with localized cancer were 105.9% and 104.1% among the active treatment and observation groups, respectively. This excellent relative survival rate in the observation group remained consistent even after stratification by tumor grade. Of the 2963 super‐elderly men with localized cancer, 252 (8.5%) with curative treatment and 1476 (49.8%) with hormone therapy were assumed to have been overtreated. The proportion of overtreatment was estimated to reach 80% after imputation. These specific survival data in super‐elderly men in the observation group can be useful in shared decision‐making for these patients and may lead to a reduction in overtreatment.     

Causes of death in men undergoing androgen suppression therapy for newly diagnosed localized or recurrent prostate cancer

BACKGROUND.

The authors estimated and characterized mortality after androgen suppression therapy (AST) use in men with newly diagnosed localized and recurrent prostate cancer.

METHODS.

The study cohorts comprised 102 men who were randomized to radiation therapy (RT) and AST and 46 men who underwent salvage AST for recurrence from a randomized trial that compared external beam RT and 6 months of AST to RT. Cox regression multivariable analyses were performed to estimate the mortality hazard ratio (HR) in men with moderate to severe as compared with no or minimal comorbidity, adjusting for age and known prostate cancer prognostic factors.

RESULTS.

After a median follow‐up of 8.4 years (interquartile range: 7.2‐9.6 years), prostate cancer‐specific mortality (PCSM) comprised 13% and 75% of all mortality in men with newly diagnosed localized and recurrent prostate cancer, respectively. There was an increased risk of death in men with moderate to severe as compared with no or minimal comorbidity (adjusted HR [AHR], 11.5; 95% confidence interval [CI], 5.2‐25.6; P < .001) in men with newly diagnosed localized prostate cancer but not in men with recurrent prostate cancer (AHR, 2.5; 95% CI, 0.2‐37.8; P = .51).

CONCLUSIONS.

The ability to measure an increase in the risk of death in men with moderate to severe as compared with no or minimal comorbidity undergoing AST decreases as the risk of PCSM increases, which may explain the discordance in the literature regarding the risk of cardiovascular death and AST use. Cancer 2008. © 2008 American Cancer Society.     

Underuse of colorectal cancer screening among men screened for prostate cancer

BACKGROUND:

Evidence suggests that colorectal cancer (CRC) screening reduces disease‐specific mortality, whereas the utility of prostate cancer screening remains uncertain. However, adherence rates for prostate cancer screening and CRC screening are very similar, with population‐based studies showing that approximately 50% of eligible US men are adherent to both tests. Among men scheduled to participate in a free prostate cancer screening program, the authors assessed the rates and correlates of CRC screening to determine the utility of this setting for addressing CRC screening nonadherence.

METHODS:

Participants (N = 331) were 50 to 70 years old with no history of prostate cancer or CRC. Men registered for free prostate cancer screening and completed a telephone interview 1 to 2 weeks before undergoing prostate cancer screening.

RESULTS:

One half of the participants who underwent free prostate cancer screening were eligible for but nonadherent to CRC screening. Importantly, 76% of the men who were nonadherent to CRC screening had a regular physician and/or health insurance, suggesting that CRC screening adherence was feasible in this group. Furthermore, multivariate analyses indicated that the only significant correlates of CRC screening adherence were having a regular physician, health insurance, and a history of prostate cancer screening.

CONCLUSIONS:

Free prostate cancer screening programs may provide a teachable moment to increase CRC screening among men who may not have the usual systemic barriers to CRC screening, at a time when they may be very receptive to cancer screening messages. In the United States, a large number of men participate in annual free prostate cancer screening programs and represent an easily accessible and untapped group that can benefit from interventions to increase CRC screening rates. Cancer 2010. © 2010 American Cancer Society.     

Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel

Background

Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study.

Methods

Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis.

Results

Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87–1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79–1.17], p = 0.69).

Conclusions

Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.     

Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated prostate‐specific antigen

BACKGROUND:

Risk models to predict prostate cancer on biopsy, whether they include only prostate‐specific antigen (PSA) or other markers, are intended for use in all men of screening age. However, the association between PSA and cancer probably depends on a man's recent screening history.

METHODS:

The authors examined the effect of prior screening on the ability to predict the risk of prostate cancer by using a previously reported, 4‐kallikrein panel that included total PSA, free PSA, intact PSA, and human kallikrein‐related peptidase 2 (hK2). The study cohort comprised 1241 men in Gothenburg, Sweden who underwent biopsy for elevated PSA during their second or later visit for the European Randomized Study of Screening for Prostate Cancer. The predictive accuracy of the 4‐kallikrein panel was calculated.

RESULTS:

Total PSA was not predictive of prostate cancer. The previously published 4‐kallikrein model increased predictive accuracy compared with total PSA and age alone (area under the curve [AUC], 0.66 vs 0.51; P < .001) but was poorly calibrated and missed many cancers. A model that was developed with recently screened men provided important improvements in discrimination (AUC, 0.67 vs 0.56; P < .001). Using this model reduced the number of biopsies by 413 per 1000 men with elevated PSA, missed 60 of 216 low‐grade cancers (Gleason score ≤6), but missed only 1 of 43 high‐grade cancers.

CONCLUSIONS:

Previous participation in PSA screening dramatically changed the performance of statistical models that were designed to predict biopsy outcome. A 4‐kallikrein panel was able to predict prostate cancer in men who had a recent screening history and provided independent confirmation that multiple kallikrein forms contribute important diagnostic information for men with elevated PSA. Cancer 2010. © 2010 American Cancer Society.