Evolving Recommendations on Prostate Cancer Screening

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.

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.


2010 ◽  
Vol 28 (15) ◽  
pp. 2493-2498 ◽  
Author(s):  
Andrew Vickers ◽  
Angel Cronin ◽  
Monique Roobol ◽  
Caroline Savage ◽  
Mari Peltola ◽  
...  

PurposeWe previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.Patients and MethodsThe study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.ResultsAddition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.ConclusionWe have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.


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.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 50-50
Author(s):  
Hong Zhang ◽  
Lois B. Travis ◽  
Edward M. Messing ◽  
Ollivier Hyrien ◽  
Rui Chen ◽  
...  

50 Background: The U.S. Preventive Services Task Force (USPSTF) recently recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. This recommendation has heightened the debate about risks and benefits of prostate cancer screening, and underscored our limited understanding of PSA-detected prostate cancer. The purpose of this study was to determine the frequency of various risks of prostate cancer based on patient characteristics and PSA levels. Methods: This population-based study used the Surveillance, Epidemiology, and End Results (SEER) program to identify men with AJCC stage T1cN0M0 disease diagnosed between 1/2004 and 12/2008. Multivariate logistic regression was conducted to model the probability of developing low (PSA <10 mg/L and Gleason score ≤6), intermediate (PSA between 10 mg/L to 20 mg/L and/or Gleason score 7), and high risk diseases (PSA ≥20 mg/L, and/or Gleason score ≥8). Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were evaluated. Among them, 47.6%, 35.9% and16.5% had low, intermediate, or high risk disease, respectively. Odds ratios (OR) of having intermediate or high risk disease in patients ≥75 years old were 4.47 (95% confidence interval (CI) 3.81 to 5.26, p<0.01) and 9.39 (95% CI 7.25 to 12.16, p<0.01), respectively, when compared with patients aged <50. Also, black men had increased ORs for intermediate and high risk disease compared with white men (OR 1.50, 95% CI 1.42 to 1.58, p<0.01 for intermediate risk disease; OR 1.84, 95% CI 1.72 to 19.97, p<0.01 for high risk disease). While men aged >75 accounted for 11.8% of the population at risk, they accounted for 24.3% of intermediate and 26.1% of high risk disease. Conclusions: A substantial number of PSA-detected prostate cancer patients have either intermediate or high risk disease at diagnosis. Men age >75 or of black race have the highest risk of presenting with intermediate or high risk disease.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5513-5513 ◽  
Author(s):  
David Eldred-Evans ◽  
Paula Burak ◽  
Martin John Connor ◽  
Emily Day ◽  
Martin Evans ◽  
...  

5513 Background: The prostate-specific antigen (PSA) test can lead to under- and over-diagnosis of prostate cancer and has not been recommended for population screening. A fast MRI scan might overcome the limitations of PSA. IP1-PROSTAGRAM is the first study to evaluate the performance of a 15-minute non-contrast MRI for prostate cancer screening in comparison to PSA. Methods: IP1-PROSTAGRAM was a prospective, population-based, screen-positive paired-cohort study. Men aged 50-69 years in the UK were invited for prostate cancer screening through seven primary care practices or community-based recruitment. Participants underwent a PSA and MRI scan (T2-weighted and diffusion). MRI was scored using PIRADS version 2.0 without knowledge of PSA; screen-positive MRI (defined as either PIRADS score 3-5 or 4-5) were compared against a screen-positive PSA defined as ≥3ng/ml. If any test was screen-positive, a systematic 12-core biopsy was performed with MRI-ultrasound image-fusion targeted biopsy to MRI suspicious areas, as appropriate. Clinically-significant cancer was defined as any Gleason score ≥3+4. The primary outcome was the proportion of screen-positive MRI at different scores; important secondary outcomes were the number of clinically-significant and insignificant cancers detected. Results: 2034 men were invited to participate of whom 408 consented and 406 were screened by both PSA and MRI (10/Oct/2018-15/May/2019). The proportion with a screen-positive MRI (score 3-5) was higher than the proportion with a screen-positive PSA (17.7% [95%CI 14.3-21.8] vs. 9.9% [95%CI 7.3-13.2]; p < 0.001). A screen-positive MRI (score 4-5) was similar to a screen-positive PSA (10.6% [95%CI 7.9-14.0] vs. 9.9% [95%CI 7.3-13.2], p = 0.71). An MRI score 3-5 or 4-5 used to denote a screen-positive MRI, compared to PSA alone, detected 14, 11 and 7 clinically-significant cancers, respectively. There were 7, 5 and 6 clinically-insignificant cancers detected, respectively. No serious adverse events occurred. Conclusions: When screening the general population for prostate cancer, MRI using a score of 4-5 to define a screen-positive test, compared to PSA alone at ≥3ng/ml, could lead to more men diagnosed with clinically-significant cancer without increasing the number of men biopsied or diagnosed with clinically-insignificant cancer. Clinical trial information: NCT03702439 .


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.


1997 ◽  
Vol 4 (2) ◽  
pp. 102-106 ◽  
Author(s):  
H G T Nijs ◽  
D M R Tordoir ◽  
J H Schuurman ◽  
W J Kirkels ◽  
F H Schroder

Abstract Objectives— To assess motives for attending a randomised population based prostate cancer screening trial, and to assess acceptance of screening and invitation procedures. Methods— First pilot of the European Randomised Study of Screening for Prostate Cancer (ERSPC; 1992/1993). Men aged 55–75 years, randomly selected from the population register of four city districts of Rotterdam, were invited by a single invitation for screening. Screening consisted of prostate specific antigen prescreening followed by either (1) digital rectal examination, transrectal ultrasound, and, on indication, biopsy, or (2) no additional screening. After screening, or in the case of non-attendance, a questionnaire was sent to a random sample of 600 attenders and 400 non-attenders, with a reminder after three weeks. Outcome measures— In both attenders and non-attenders: Knowledge of prostate cancer, attitudes towards screening, motives for attending, procedural aspects and sociodemographic characteristics. In attenders, acceptance of screening procedures. Results— The response rate for the questionnaire was 76%: 94% in attenders and 42% in non-attenders. The main reasons for attending were expected personal benefit (76%) and scientific value (39%), and those for not attending were the absence of urological complaints (41%) and anticipated pain or discomfort (24%). Uptake of screening was 32%, which increased to a sustained 42% in following years. Attenders, compared with non-attenders, were significantly younger, more often married, better educated, and had higher perceived health status, more knowledge about prostate cancer, and a more positive attitude towards screening. Information materials and invitation procedure were adequate. Screening procedures were well accepted (high report marks and satisfaction, and 95% would attend for rescreening). A single prostate specific antigen determination was liked less than a combination of all three screening modalities. Conclusions— (1) The main reasons for attending are personal benefit and science, and those for not attending were absence of urological complaints and anticipated pain or discomfort; (2) knowledge, attitudes, and motives for attending are comparable with other screening programmes; hence, for population based prostate cancer screening, known health promotional aspects should be carefully considered; (3) prostate specific antigen, digital rectal examination and transrectal ultrasound are acceptable to attenders.


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