Overdiagnosis and Overtreatment of Prostate Cancer

Author(s):  
Ian M. Thompson

Overview: Prostate cancer is a ubiquitous disease, affecting as many as two-thirds of men in their 60s. Through widespread prostate-specific antigen (PSA) testing, increasing rates of prostate biopsy, and increased sampling of the prostate, a larger fraction of low-grade, low-volume tumors have been detected, consistent with tumors often found at autopsy. These tumors have historically been treated in a manner similar to that used for higher-grade tumors but, more recently, it has become evident that with a plan of active surveillance that reserves treatment for only those patients whose tumors show evidence of progression, very high disease-specific survival can be achieved. Unfortunately, the frequency of recommendation of an active surveillance strategy in the United States is low. An alternative strategy to improve prostate cancer detection is through selected biopsy of those men who are at greater risk of harboring high-grade, potentially lethal cancer. This strategy is currently possible through the use of risk assessment tools such as the Prostate Cancer Prevention Trial Risk Calculator ( www.prostate.cancer.risk.calculator.com ) as well as others. These tools can predict with considerable accuracy a man's risk of low-grade and high-grade cancer, allowing informed decision making for the patient with a goal of detection of high-risk disease. Ultimately, other biomarkers including PCA3, TMPRSS2:ERG, and [-2]proPSA will likely aid in discriminating these two types of cancer before biopsy.

2019 ◽  
Vol 17 (5) ◽  
pp. 506-513 ◽  
Author(s):  
Brandon R. Mason ◽  
James A. Eastham ◽  
Brian J. Davis ◽  
Lance A. Mynderse ◽  
Thomas J. Pugh ◽  
...  

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.


2014 ◽  
Vol 32 (27) ◽  
pp. 3033-3038 ◽  
Author(s):  
Mohummad Minhaj Siddiqui ◽  
Kathryn M. Wilson ◽  
Mara M. Epstein ◽  
Jennifer R. Rider ◽  
Neil E. Martin ◽  
...  

Purpose Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease. Patients and Methods Among 49,405 US men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders. Results Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment. Conclusion Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Salonee Shah ◽  
Kerri Beckmann ◽  
Mieke Van Hemelrijck ◽  
Ben Challacombe ◽  
Rick Popert ◽  
...  

Abstract Background The routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy’s and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa. Methods Demographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort. Discussion A relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79–3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94–3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53–0.98). Conclusion An organised biopsy surveillance approach, via two different AS pathways according to the patient’s diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.


Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 641 ◽  
Author(s):  
Teng-Kai Yang ◽  
Pi-Chun Chuang ◽  
Amy Ming-Fang Yen ◽  
Hsiu-Hsi Chen ◽  
Sam Li-Sheng Chen

(1) Background: A simulation approach for prostate cancer (PrCa) with a prostate-specific antigen (PSA) test incorporating genetic information provides a new avenue for the development of personalized screening for PrCa. Going by the evidence-based principle, we use the simulation method to evaluate the effectiveness of mortality reduction resulting from PSA screening and its utilization using a personalized screening regime as opposed to a universal screening program. (2) Methods: A six-state (normal, over-detected, low-grade, and high-grade PrCa in pre-clinical phase, and low-grade and high-grade PrCa in clinical phase) Markov model with genetic and PSA information was developed after a systematic review of genetic variant studies and dose-dependent PSA studies. This gene‒PSA-guided model was used for personalized risk assessment and risk stratification. A computer-based simulated randomized controlled trial was designed to estimate the reduction of mortality achieved by three different screening methods, personalized screening, universal screening, and a non-screening group. (3) Results: The effectiveness of PrCa mortality reduction for a personalized screening program compared to a non-screening group (22% (9%‒33%)) was similar to that noted in the universal screening group (20% (7%‒21%). However, a personalized screening program could dispense with 26% of unnecessary PSA testing, and avoid over-detection by 2%. (4) Conclusions: Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction (as happens with the universal screening program).


Author(s):  
Rianne J. Hendriks ◽  
Marloes M. G. van der Leest ◽  
Bas Israël ◽  
Gerjon Hannink ◽  
Anglita YantiSetiasti ◽  
...  

Abstract Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.


2008 ◽  
Vol 4 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Kamilah B. Thomas ◽  
Sean L. Simpson ◽  
Will L. Tarver ◽  
Clement K. Gwede

African American and White men have the highest rates of prostate cancer in the United States. Families represent important social contexts within which illness occurs.The purpose of this study is to explore whether prostate-specific antigen (PSA) testing is associated with instrumental and informational social support from family members among a sample of Black and White men aged 45 and older. Data from the 2005 Health Information National Trends Survey were analyzed using logistic regression. The dependent variable was having a PSA test within the past year or less. The independent variables consisted of selected demographic and family informational and instrumental social support variables. The statistically significant variables included age and having a family member with cancer. Additional studies to elucidate the mechanisms of social support from family for prostate cancer are needed.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Daniel W. Smith ◽  
Diliana Stoimenova ◽  
Khadijah Eid ◽  
Al Barqawi

Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.


2017 ◽  
Vol 63 (8) ◽  
pp. 722-725 ◽  
Author(s):  
Marcus V. Sadi

Summary Screening of prostate cancer with prostate-specific antigen (PSA) is a highly controversial issue. One part of the controversy is due to the confusion between population screening and early diagnosis, another derives from problems related to the quality of existing screening studies, the results of radical curative treatment for low grade tumors and the complications resulting from treatments that affect the patient’s quality of life. Our review aimed to critically analyze the current recommendations for PSA testing, based on new data provided by the re-evaluation of the ongoing studies and the updated USPSTF recommendation statement, and to propose a more rational and selective use of PSA compared with baseline values obtained at an approximate age of 40 to 50 years.


Author(s):  
Otis W. Brawley ◽  
Ian M. Thompson ◽  
Henrik Grönberg

Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1223
Author(s):  
Filippo Pesapane ◽  
Marzia Acquasanta ◽  
Rosario Di Meo ◽  
Giorgio Maria Agazzi ◽  
Priyan Tantrige ◽  
...  

(1) Background: the study of dynamic contrast enhancement (DCE) has a limited role in the detection of prostate cancer (PCa), and there is a growing interest in performing unenhanced biparametric prostate-MRI (bpMRI) instead of the conventional multiparametric-MRI (mpMRI). In this study, we aimed to retrospectively compare the performance of the mpMRI, which includes DCE study, and the unenhanced bpMRI, composed of only T2-weighted imaging and diffusion-weighted imaging (DWI), in PCa detection in men with elevated prostate-specific-antigen (PSA) levels. (2) Methods: a 1.5 T MRI, with an endorectal-coil, was performed on 431 men (aged 61.5 ± 8.3 years) with a PSA ≥4.0 ng/mL. The bpMRI and mpMRI tests were independently assessed in separate sessions by two readers with 5 (R1) and 3 (R2) years of experience. The histopathology or ≥2 years follow-up served as a reference standard. The sensitivity and specificity were calculated with their 95% CI, and McNemar’s and Cohen’s κ statistics were used. (3) Results: in 195/431 (45%) of histopathologically proven PCa cases, 62/195 (32%) were high-grade PCa (GS ≥ 7b) and 133/195 (68%) were low-grade PCa (GS ≤ 7a). The PCa could be excluded by histopathology in 58/431 (14%) and by follow-up in 178/431 (41%) of patients. For bpMRI, the sensitivity was 164/195 (84%, 95% CI: 79–89%) for R1 and 156/195 (80%, 95% CI: 74–86%) for R2; while specificity was 182/236 (77%, 95% CI: 72–82%) for R1 and 175/236 (74%, 95% CI: 68–80%) for R2. For mpMRI, sensitivity was 168/195 (86%, 95% CI: 81–91%) for R1 and 160/195 (82%, 95% CI: 77–87%) for R2; while specificity was 184/236 (78%, 95% CI: 73–83%) for R1 and 177/236 (75%, 95% CI: 69–81%) for R2. Interobserver agreement was substantial for both bpMRI (κ = 0.802) and mpMRI (κ = 0.787). (4) Conclusions: the diagnostic performance of bpMRI and mpMRI were similar, and no high-grade PCa was missed with bpMRI.


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