NCCN: Continuing Education
Accreditation Statement
This activity has been designed to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center‘s Commission on Accreditation.
NCCN designates this educational activity for a maximum of 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.
National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-16-005-H01-P
All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/78544; and 4) view/print certificate.
Release date: May 12, 2016; Expiration date: May 12, 2017
Learning Objectives:
Upon completion of this activity, participants will be able to:
Integrate into professional practice the updates to NCCN Guidelines for Prostate Cancer Early Detection
Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Prostate Cancer Early Detection
NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016
Version 2.2016 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 14, 5; 10.6004/jnccn.2016.0060
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Overview
In men, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death. Prostate cancer represents a spectrum of disease that ranges from nonaggressive and slow-growing disease that does not require treatment to aggressive and fast-growing disease that does necessitate treatment. Early detection strategies should maximize the detection of aggressive prostate cancer that is potentially curable, while minimizing unnecessary procedures and the detection of indolent disease. Population-based prostate cancer screening studies have shown survival benefits using prostate-specific antigen (PSA) levels, sometimes in combination with a digital rectal examination or other ancillary tests.1–5 Therefore, the NCCN Prostate Cancer Early Detection Panel supports the use of PSA testing for the early detection of prostate cancer in informed, healthy men in specific age groups and encourages active surveillance or observation for appropriate candidates in whom low-risk disease is
NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016
Version 2.2016 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 14, 5; 10.6004/jnccn.2016.0060
The issues discussed by the panel this year are described in these NCCN Guidelines Insights. Changes to the NCCN Guidelines algorithms are indicated with blue font herein.
Patient Selection for Biopsies
PSA testing results in the diagnosis of high-grade tumors at a potentially earlier, more curable stage than clinical detection. However, PSA testing has poor specificity and often produces false-positive results, which contribute to patient anxiety and increased costs and potential complications associated with unnecessary biopsies (eg, drug-resistant Escherichia coli infections). PSA testing also leads to the detection of much indolent disease (overdetection), which contributes to overtreatment, patient stress, possible complications, and inconvenience of active surveillance. Additional techniques used with PSA testing have the potential to refine patient selection for biopsies, decrease unnecessary biopsies, reduce overdetection, and increase biopsy specificity, without missing a substantial number of aggressive cancers. Such improvements to PSA screening could make it a more valuable tool for men who choose to participate in an early detection program by increasing the benefits while decreasing the risks.
Therefore, the panel discussed the roles of biomarker testing and advanced imaging to refine patient selection for initial and repeat biopsies, as described herein.
Biomarker Tests
When a patient meets the standards for biopsy, patients and physicians may wish to further define the probability of cancer before proceeding to biopsy with its associated risks. Several biomarker tests have been developed with the goals of refining patient selection for biopsies, decreasing unnecessary biopsies, and increasing the specificity of cancer
NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016
Version 2.2016 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 14, 5; 10.6004/jnccn.2016.0060
In the 2015 version of these guidelines, the panel recommended consideration of percent free PSA, 4Kscore, or Prostate Health Index (PHI) in patients with PSA levels greater than 3 ng/mL who have not had a biopsy. For men who have had at least one prior negative biopsy and are thought to be at higher risk, the panel recommended the same tests or PCA3.6–16
Multiple institutional review comments requested that the panel consider adding ConfirmMDx in the repeat biopsy setting based on data showing that it has potential value for patients with an elevated PSA and prior negative biopsy. ConfirmMDx is a tissue-based, multiplex epigenetic assay that aims to improve the stratification of men being considered for repeat biopsy. Hypermethylation of the promoter regions of GSTP1, APC, and RASSF1 are assessed in core biopsy tissue samples.17,18 The panel found the available data convincing and unanimously agreed (with several abstentions) to add consideration of ConfirmMDx for men contemplating repeat biopsy (see PROSD-4; above).
The panel then discussed how to compare the various recommended tests and whether they could recommend one or more tests over the others. As the list of potential assays grows, the NCCN Guidelines Panel believes that clinicians and patients will need more guidance. These tests have different objectives (eg, improving sensitivity, reducing false-positives), different impacts on downstream outcomes (eg, mortality reduction, reduced overdiagnosis), and are used in different settings (ie, initial or repeat biopsy). Ideally, the negative predictive value and positive predictive value (PPV) for any cancer and for high-grade cancer; the number of biopsies avoided; and the number of aggressive cancers missed for each test could be compared. However, studies for the different assays have been performed with different cohorts, settings, time points, and reported outcomes. Head-to-head comparisons have been performed in Europe for some of these tests, used independently or in combinations in the initial or repeat biopsy settings, but sample sizes were small and results varied.19–26
Therefore, the panel emphasized the following points: no biomarker test can be recommended over any other; a biomarker assay can be performed in addition to multiparametric MRI (mp-MRI)/refined biopsy techniques in the repeat biopsy setting (discussed in the following section); the optimal order of biomarker tests and imaging is unknown; and it remains unclear how to interpret results of multiple tests in individual patients, especially when results are contradictory. The panel further emphasized that results of any of these tests, when performed, should be used as part of discussions between clinician and patient to assist in decisions regarding whether to proceed with biopsy.
Multiparametric MRI
Considerable interest exists for the use of novel MRI, most notably mp-MRI, to select patients who need a prostate biopsy or to guide needle placement during the procedure, although data supporting its use in these settings are currently limited.27–29 The goals of using MRI to inform the decision of whether to perform a biopsy include reducing the number of men undergoing biopsy, reducing the detection of indolent disease (and thus the risks of overdetection and overtreatment), and improving the detection of clinically significant disease through targeted biopsies (see “Advanced Biopsy Techniques,” this page).
The panel discussed the use of MRI before initial biopsy based on the available data analyzing the clinical utility of mp-MRI for patient selection in the initial biopsy setting. In a prospective study of 223 biopsy-naïve men with an elevated PSA level, all men underwent standard transrectal ultrasound (TRUS) biopsies in addition to mp-MRI.28 Not performing a biopsy in men with PI-RADS 1/2 lesions on MRI would have reduced the number of men requiring biopsy by 36%, reduced the identification of low-risk prostate cancer by 87%, and increased the yield of intermediate/high-risk tumors by 18%, but would have missed 15 intermediate/high-risk tumors (6.7% of study population). A trial at a single hospital-based practice randomized 130 biopsy-naïve men with elevated PSA levels to either TRUS-guided random biopsy alone or to prebiopsy mp-MRI, TRUS-guided random biopsy, and cognitive MRI/TRUS fusion targeted biopsy.29 In this study, 13 tumors with Gleason score 3 + 4 would have been missed in the 53 evaluable men in the mp-MRI group based on MRI results (24.5%). Additional clinical trials are underway to assess the value of MRI for diagnosis in the prebiopsy setting (ClinicalTrials.gov identifiers: NCT02131207, NCT02485379, and NCT02450266).
Based on these studies, the panel agreed that the use of MRI to exclude men from biopsies could lead to many clinically significant cancers being missed. Overall, the panel believes that MRI alone should not be used to determine whether to perform an initial biopsy, and emphasizes that a negative MRI is not a reason to forego biopsy in men with strong indications for a first-time biopsy. All men with indications for biopsy should receive the standard 12-core TRUS-guided biopsy regardless of MRI results, with possible additional targeted biopsies. The panel therefore added a footnote stating that MRI is not currently routinely recommended before initial biopsy to accentuate these points (see PROSD-3; page 512). Additionally, the panel acknowledged emerging data showing that mp-MRI followed by lesion targeting may increase the detection of higher-risk disease while lowering the detection of lower-risk disease (see “Advanced Biopsy Techniques,” below).30
Advanced Biopsy Techniques
Targeted, template, and saturation biopsy techniques are being studied in hope of improving detection of clinically significant prostate cancer while minimizing the detection of indolent disease.31–35 Targeted biopsy techniques include cognitive or visual targeting (ultrasound-guided, based on an MRI image), MRI/TRUS fusion platforms (merging a stored MRI image with a real-time ultrasound image), and direct in-bore magnetic resonance–guided biopsy (performed by an interventional radiologist while the patient is in the scanner).31–33 In saturation biopsies, cores are systematically collected every few millimeters across the entire prostate to improve detection over that of a standard 12-core biopsy. Saturation biopsies can be performed via transrectal or transperineal approaches. Another advanced technique is transperineal template biopsy, which does not saturate every single area but instead systematically samples anterior, mid, posterior, and basal zones for approximately 24 to 32 cores.36
For the 2016 guideline update, the NCCN Guidelines Panel discussed the role of targeted biopsies in the initial and repeat settings, as described in these Insights.
Targeted Biopsies in the Initial Biopsy Setting
The panel discussed the data on targeted biopsy techniques for biopsy-naïve patients. In a prospective study of 223 biopsy-naïve men with elevated PSA levels, all men had standard TRUS biopsies and mp-MRI.28 Participants with suspicious or equivocal lesions (PI-RADS 3–5) then underwent MRI-guided biopsy. TRUS biopsies detected 126 of 142 cases (88.7%), including 47 cases classified as low risk. The MRI-guided biopsies identified an additional 16 cases of intermediate/high-risk prostate cancer and led to the reclassification of 13 cases from low risk to intermediate/high risk. Therefore, the addition of mp-MRI with targeted biopsies for suspicious or equivocal lesions to standard biopsy allowed the identification of clinically significant disease in an additional 13% of the study population. A single-center trial randomized 130 biopsy-naïve men to receive either TRUS-guided random biopsy alone or prebiopsy mp-MRI, TRUS-guided random biopsy, and cognitive MRI/TRUS fusion targeted biopsy.29 Similar rates of detection of prostate cancer (64% vs 57%; P=.5) and clinically significant cancer (55% vs 45%; P=.8) were seen in the 2 arms.
In a single-institution prospective cohort study, 1,003 men with elevated PSA levels or an abnormal digital rectal examination and lesions visible on mp-MRI underwent both MRI/ultrasound fusion targeted and standard biopsy.30 In this study, 196 men had no prior biopsy, and results appear to be similar in the biopsy-naïve subgroup compared with the entire cohort. In the full cohort, 170 men had pathology results available after radical prostatectomy: 8 men (4.7%) had intermediate- or high-risk cancers that would have been missed based on targeted biopsy results of no or low-risk cancer, and 44 men (26%) had intermediate- or high-risk cancers that would have been missed based on standard biopsy results of no or low-risk cancer. The sensitivities of targeted and standard biopsies for detecting intermediate- or high-grade cancer were 77% and 53%, respectively, whereas the specificities of the approaches were similar, at 68% and 66%, respectively. Combining both biopsy techniques increased sensitivity to 85% but decreased specificity to 49%. The effect of targeted biopsies on clinical outcomes is still unknown.
The panel did not believe that the current data for the use of targeted biopsies in the initial biopsy setting were sufficient to recommend them over standard biopsies in this setting. However, the panel agreed that it was important to acknowledge the emerging data showing that mp-MRI followed by lesion targeting may increase the detection of clinically significant, higher-risk disease (Gleason ≥4 + 3) while lowering the detection of lower-risk disease (Gleason 6 or lower-volume 3 + 4) (see PROSD-3; page 512).
Targeted Biopsies in the Repeat Biopsy Setting
A negative biopsy does not preclude a diagnosis of prostate cancer on subsequent biopsy, and repeat biopsies are often considered in men for whom clinical suspicion of high-risk disease persists. Reviewers requested that the NCCN Guidelines Panel consider the addition of mp-MRI–guided biopsy techniques for patients with prior negative biopsies and for patients in whom a high suspicion exists for clinically significant prostate cancer. These individuals pointed out that increasing data are demonstrating the superiority of MRI-targeted biopsy techniques over standard biopsy for the detection of clinically significant/high-grade prostate cancer after a negative biopsy, and therefore requested that the panel consider putting more emphasis on these approaches by adding them to the algorithm. The panel was also asked to consider where targeted biopsy belonged in the diagnostic algorithm relative to the recommended biomarkers assays in this repeat biopsy setting.
In a prospective study that included 347 patients with findings suspicious for prostate cancer, many of whom had 1 or more previous negative biopsies, all patients received mp-MRI and those with abnormal findings proceeded to MRI/TRUS fusion targeted biopsies.27 The outcome was defined as improved detection in targeted cores, with significantly more cancer detected in targeted cores than in systematic biopsies (30% vs 8.2%). Approximately 12% of men without MRI-suspicious lesions were diagnosed with intermediate-risk tumors. In this study, the cancer detection rate was 51% in men with previous negative biopsies. In a prospective cohort study of 1,003 men undergoing both MRI-targeted and standard biopsy (see “Targeted Biopsies in the Initial Biopsy Setting,” page 515), Siddiqui et al30 noted that targeted biopsies were associated with the detection of high-risk cancer and decreased detection of low-risk cancer.30 A recent meta-analysis of 16 studies (1,926 men) also showed that MRI-targeted biopsy improved detection of clinically significant prostate cancer in biopsy-naïve men compared with standard TRUS biopsy.37
Although the NCCN Guidelines Panel found the increasing evidence convincing, they also pointed out that the publications come from only a few centers with a small number of clinicians and radiologists. No data to date show that these techniques will work in other oncology settings (eg, community hospitals). Overall, the panel believes that the level of evidence has risen to the level needed for targeted biopsies to be considered in the repeat biopsy setting. The panel agreed to add mp-MRI and/or refined biopsy techniques for consideration in men with benign findings or focal high-grade prostatic intraepithelial neoplasia (see PROSD-4; page 513). These techniques include saturation biopsy strategies and the use of mp-MRI followed by a targeted biopsy technique based on the results, and these techniques can be considered before or after biomarker tests (discussed previously) to aid in patient/clinician discussions.
Screening in High-Risk Populations
Certain populations (eg, African Americans, men with a first-degree relative with prostate cancer) have a higher risk of developing prostate cancer.38–42 At the meeting for the 2016 guideline update, the panel discussed the role that race and genetic susceptibility play in prostate cancer and whether or not screening recommendations should be altered for high-risk men.
Race
African American men have a 64% higher incidence of prostate cancer and 2.3-fold increase in prostate cancer mortality compared with white men, and are approximately 4 times more likely to be diagnosed with metastatic disease.38,43 Furthermore, autopsy data indicate that prostate cancer may undergo transformation to aggressive disease earlier in African American men than in white men.43 Factors that contribute to this racial disparity may include differences in genetic risk factors, environmental exposures, and patient and physician behaviors; decreased access to high-quality health care, including cancer early detection and follow-up care; delays in diagnosis; and suboptimal treatment.44–47
Two institutional reviewers introduced the topic of prostate cancer early detection in African Americans. In particular, they questioned whether discussions about screening should be initiated earlier with this population, if screening should start earlier in this group, and whether these men should be screened more intensively. The panel discussion that ensued found a lack of data to inform the best strategy for prostate cancer screening in these men. Prostate cancer screening has been best studied in white men; data on screening in diverse and high-risk populations are lacking. In the PLCO trial, approximately 4.4% of the participants were African American and 6.9% had a positive family history, but no subset analyses were performed for black men.48 In the ERSPC trial, no information on race or family history was reported.3
The panel discussed data suggesting that African American men have an earlier onset of prostate cancer, which might support earlier screening initiation. An analysis of SEER data from 2010 found that non-Hispanic black men were diagnosed with prostate cancer an adjusted average of 1.2 years earlier than non-Hispanic white men,49 whereas an older SEER analysis found that African American men were diagnosed at an average of 3 years younger than white men.50 A retrospective population-based cohort study in the United Kingdom found that black men were diagnosed an adjusted average of 5.1 years earlier than white men.51 Another study estimated that African American men have an almost 2-fold higher risk of being diagnosed with prostate cancer before the age of 45 years compared with white men.50
Although the panel members agreed that this topic cannot and should not be ignored, they believe that data do not support earlier or more intensive screening at this time. Race is, however, included as a baseline evaluation factor for risk assessment that can be used to help decide when a man should begin the early detection process within the NCCN recommended ages of 45 to 75 years. Clearly, African American men are at a higher risk for prostate cancer and prostate cancer mortality, but the effects of earlier or more intensive screening on cancer outcomes and screening-related harms in this populations are not clear. The panel also noted that a baseline PSA value is a stronger predictive factor than a positive family history or race.52 Therefore, although these individuals may require a higher level of vigilance and potentially different considerations when analyzing the results of screening tests, the panel did not provide separate screening recommendations for this patient population at this time. Instead, they added a footnote to emphasize these points (see PROSD-2; page 511).
BRCA1 and BRCA2 Mutations
Germline BRCA1 and BRCA2 mutations (associated with hereditary breast and/or ovarian cancer syndrome) have been associated with an increased risk for prostate.53–61 In particular, BRCA2 mutations have been associated with a 2- to 6-fold increase in the risk for prostate cancer, whereas the association between BRCA1 mutations and an increased risk for prostate cancer is less consistent.54,56,57,61–63 Furthermore, prostate cancer in men with germline BRCA mutations appears to have a more aggressive phenotype and is associated with significantly reduced survival times than prostate cancer in those who do not have the gene.64–68
The panel received an external submission requesting that genetic risk assessment be recommended in the NCCN Guidelines for Prostate Cancer Early Detection based on recommendations in the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian. These latter guidelines include personalized risk assessment, genetic counseling, and possible genetic testing for individuals with a personal history of prostate cancer and 1 or more close blood relatives with breast cancer (age ≤50 years) or ovarian cancer, or 2 relatives with breast, pancreatic, or prostate cancer (Gleason score ≥7). Individuals meeting these criteria are considered at risk of harboring a BRCA1/2 mutation.69 These guidelines note that individuals with a family history only can also be considered for genetic testing if no living affected family member is available, but that the limitations of testing in unaffected relatives should be discussed.69
Although the panel did not believe that the NCCN Guidelines for Prostate Cancer Early Detection should list recommendations for genetic risk assessment, they did agree that men should be asked about the presence of known BRCA1/2 mutations in their families. Therefore, the panel added “Family history of BRCA1/2 mutations” to the baseline evaluation that precedes discussions on the risks and benefits of prostate cancer screening (see PROSD-2; page 511). If there is a known or suspected cancer susceptibility gene, referral to a cancer genetics professional is recommended. Information regarding BRCA1/2 gene status should be used as part of the discussion about prostate cancer screening; patients may not be aware of the increased risk of prostate cancer associated with these mutations. Some panel members believe that men with known germline BRCA1/2 mutations should be encouraged to undergo PSA testing.
The panel then discussed whether a known BRCA1 or BRCA2 mutation would impact prostate cancer screening. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian (available at NCCN.org) recommend that men with BRCA2 mutations begin prostate cancer screening at age 40 years and that those with BRCA1 mutations consider the same.69 Results were recently reported from the first round of screening in the IMPACT study, which enrolled men aged 40 to 69 years with germline BRCA1/2 mutations and a control group of men with wild-type BRCA1/2 related to mutation carriers.70 Although no difference was shown between carriers and controls in the rate of prostate cancer detection or the PPV of biopsy for detecting cancer in men with PSA levels greater than 3.0 ng/mL, a significant difference was seen in the PPV of biopsy for detecting intermediate/high-grade cancer in BRCA2 carriers with PSA levels greater than 3.0 ng/mL (2.4% vs 0.7%; P=.04). Future rounds of screening in this trial may help inform the best strategy for screening in this high-risk population. Therefore, the panel noted that, although these mutations are clearly risk factors, data supporting a change in the PSA screening and biopsy recommendations for these men relative to those without mutations are insufficient at this time. The panel also noted that, as with race, baseline PSA value is a stronger predictive factor than a positive family history.52
Conclusions
The NCCN Guideline revisions for the 2016 update highlight several techniques designed to improve the identification of significant cancer while avoiding the detection of indolent disease. Advanced biopsy techniques, including targeted biopsies, are one promising technique to help advance these goals. In addition, patient selection for biopsies can be refined through the appropriate use of biomarker assays and advanced imaging, thereby minimizing unnecessary procedures and limiting the detection of indolent disease. In the future, data may inform more individualized, risk-based approaches to prostate cancer early detection that take into account race, genetic predisposition, and family history.
References
- 1.↑
Andriole GL. Update of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Recent Results Cancer Res 2014;202:53–57.
- 2.
Andriole GL, Crawford ED, Grubb RL III et al.. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104:125–132.
- 3.↑
Schroder FH, Hugosson J, Roobol MJ et al.. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–1328.
- 4.
Schroder FH, Hugosson J, Roobol MJ et al.. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012;366:981–990.
- 5.↑
Schroder FH, Hugosson J, Roobol MJ et al.. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014;384:2027–2035.
- 6.↑
Catalona WJ, Partin AW, Sanda MG et al.. A multicenter study of [-2]proprostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. J Urol 2011;185:1650–1655.
- 7.
Filella X, Gimenez N. Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 2013;51:729–739.
- 8.
Lazzeri M, Haese A, Abrate A et al.. Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int 2013;112:313–321.
- 9.
Loeb S. Prostate cancer: Prostate Health Index—improving screening in men with family history. Nat Rev Urol 2013;10:497–498.
- 10.
Partin AW, Brawer MK, Subong EN et al.. Prospective evaluation of percent free-PSA and complexed-PSA for early detection of prostate cancer. Prostate Cancer Prostatic Dis 1998;1:197–203.
- 11.
Bryant RJ, Sjoberg DD, Vickers AJ et al.. Predicting high-grade cancer at tencore prostate biopsy using four kallikrein markers measured in blood in the ProtecT Study. J Natl Cancer Inst 2015;107:pii: djv095.
- 12.
Parekh DJ, Punnen S, Sjoberg DD et al.. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol 2015;68:464–470.
- 13.
Vickers A, Cronin A, Roobol M et al.. Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication. J Clin Oncol 2010;28:2493–2498.
- 14.
Vickers AJ, Gupta A, Savage CJ et al.. A panel of kallikrein marker predicts prostate cancer in a large, population-based cohort followed for 15 years without screening. Cancer Epidemiol Biomarkers Prev 2011;20:255–261.
- 15.
Vickers AJ. Markers for the early detection of prostate cancer: some principles for statistical reporting and interpretation. J Clin Oncol 2014;32:4033–4034.
- 16.↑
Wei JT, Feng Z, Partin AW et al.. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol 2014;32:4066–4072.
- 17.↑
Stewart GD, Van Neste L, Delvenne P et al.. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol 2013;189:1110–1116.
- 18.↑
Partin AW, Van Neste L, Klein EA et al.. Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol 2014;192:1081–1087.
- 19.↑
Auprich M, Augustin H, Budaus L et al.. A comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostate-specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy. BJU Int 2012;109:1627–1635.
- 20.
Boegemann M, Stephan C, Cammann H et al.. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged </=65 years. BJU Int 2016;117:72–79.
- 21.
De Luca S, Passera R, Bollito E et al.. Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy. Anticancer Res 2014;34:7159–7165.
- 22.
De Luca S, Passera R, Fiori C et al.. Prostate health index and prostate cancer gene 3 score but not percent-free prostate specific antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy. Urol Oncol 2015;33:424.e417–423.
- 23.
Ferro M, Bruzzese D, Perdona S et al.. Prostate Health Index (Phi) and prostate cancer antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml. PLoS One 2013;8:e67687.
- 24.
Perdona S, Bruzzese D, Ferro M et al.. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy. Prostate 2013;73:227–235.
- 25.
Porpiglia F, Russo F, Manfredi M et al.. The roles of multiparametric magnetic resonance imaging, PCA3 and prostate health index-which is the best predictor of prostate cancer after a negative biopsy? J Urol 2014;192:60–66.
- 26.↑
Scattoni V, Lazzeri M, Lughezzani G et al.. Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy. J Urol 2013;190:496–501.
- 27.↑
Kuru TH, Roethke MC, Seidenader J et al.. Critical evaluation of magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy for detection of prostate cancer. J Urol 2013;190:1380–1386.
- 28.↑
Pokorny MR, de Rooij M, Duncan E et al.. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014;66:22–29.
- 29.↑
Tonttila PP, Lantto J, Paakko E et al.. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsy-naive men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. Eur Urol 2016;69:419–425..
- 30.↑
Siddiqui MM, Rais-Bahrami S, Turkbey B et al.. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA 2015;313:390–397.
- 31.↑
Rastinehad AR, Turkbey B, Salami SS et al.. Improving detection of clinically significant prostate cancer: MRI/TRUS fusion-guided prostate biopsy. J Urol 2014;191:1749–1754.
- 32.
Robertson NL, Emberton M, Moore CM. MRI-targeted prostate biopsy: a review of technique and results. Nat Rev Urol 2013;10:589–597.
- 33.↑
Puech P, Rouviere O, Renard-Penna R et al.. Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy—prospective multicenter study. Radiology 2013;268:461–469.
- 34.
Abdollah F, Novara G, Briganti A et al.. Trans-rectal versus trans-perineal saturation rebiopsy of the prostate: is there a difference in cancer detection rate? Urology 2011;77:921–925.
- 35.↑
Nelson AW, Harvey RC, Parker RA et al.. Repeat prostate biopsy strategies after initial negative biopsy: meta-regression comparing cancer detection of transperineal, transrectal saturation and MRI guided biopsy. PLoS One 2013;8:e57480.
- 36.↑
Sivaraman A, Sanchez-Salas R, Barret E et al.. Transperineal template-guided mapping biopsy of the prostate. Int J Urol 2015;22:146–151.
- 37.↑
Schoots IG, Roobol MJ, Nieboer D et al.. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol 2015;68:438–450.
- 38.↑
SEER Stat Fact Sheets: Prostate Cancer. 2015. Available at: http://seer.cancer.gov/statfacts/html/prost.html. Accessed April 28, 2015.
- 39.
Bratt O. Hereditary prostate cancer: clinical aspects. J Urol 2002;168:906–913.
- 40.
Carter BS, Beaty TH, Steinberg GD et al.. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A 1992;89:3367–3371.
- 41.
Chen YC, Page JH, Chen R, Giovannucci E. Family history of prostate and breast cancer and the risk of prostate cancer in the PSA era. Prostate 2008;68:1582–1591.
- 42.↑
Grill S, Fallah M, Leach RJ et al.. Incorporation of detailed family history from the Swedish Family Cancer Database into the PCPT risk calculator. J Urol 2015;193:460–465.
- 43.↑
Powell IJ, Bock CH, Ruterbusch JJ, Sakr W. Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol 2010;183:1792–1796.
- 44.↑
Barocas DA, Grubb R III, Black A et al.. Association between race and follow-up diagnostic care after a positive prostate cancer screening test in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. Cancer 2013;119:2223–2229.
- 45.
Mahal BA, Aizer AA, Ziehr DR et al.. Trends in disparate treatment of African American men with localized prostate cancer across National Comprehensive Cancer Network risk groups. Urology 2014;84:386–392.
- 46.
Yamoah K, Johnson MH, Choeurng V et al.. Novel biomarker signature that may predict aggressive disease in african american men with prostate cancer. J Clin Oncol 2015;33:2789–2796.
- 47.↑
Zhang H, Messing EM, Travis LB et al.. Age and racial differences among PSA-detected (AJCC stage T1cN0M0) prostate cancer in the U.S.: a population-based study of 70,345 men. Front Oncol 2013;3:312.
- 48.↑
Andriole GL, Crawford ED, Grubb RL III et al.. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–1319.
- 49.↑
Robbins HA, Engels EA, Pfeiffer RM, Shiels MS. Age at cancer diagnosis for blacks compared with whites in the United States. J Natl Cancer Inst 2015;107: pii: dju489.
- 50.↑
Karami S, Young HA, Henson DE. Earlier age at diagnosis: another dimension in cancer disparity? Cancer Detect Prev 2007;31:29–34.
- 51.↑
Metcalfe C, Evans S, Ibrahim F et al.. Pathways to diagnosis for black men and white men found to have prostate cancer: the PROCESS cohort study. Br J Cancer 2008;99:1040–1045.
- 52.↑
Vertosick EA, Poon BY, Vickers AJ. Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening. J Urol 2014;192:724–728.
- 53.↑
Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 1999;91:1310–1316.
- 54.↑
Agalliu I, Gern R, Leanza S, Burk RD. Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations. Clin Cancer Res 2009;15:1112–1120.
- 55.
Ford D, Easton DF, Bishop DT et al.. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 1994;343:692–695.
- 56.↑
Gallagher DJ, Gaudet MM, Pal P et al.. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res 2010;16:2115–2121.
- 57.↑
Kirchhoff T, Kauff ND, Mitra N et al.. BRCA mutations and risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res 2004;10:2918–2921.
- 58.
Leongamornlert D, Mahmud N, Tymrakiewicz M et al.. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer 2012;106:1697–1701.
- 59.
Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol 2004;22:735–742.
- 60.
Tulinius H, Olafsdottir GH, Sigvaldason H et al.. The effect of a single BRCA2 mutation on cancer in Iceland. J Med Genet 2002;39:457–462.
- 61.↑
van Asperen CJ, Brohet RM, Meijers-Heijboer EJ et al.. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 2005;42:711–719.
- 62.
Mersch J, Jackson MA, Park M et al.. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 2015;121:269–275.
- 63.↑
Moran A, O'Hara C, Khan S et al.. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer 2012;11:235–242.
- 64.↑
Castro E, Goh C, Olmos D et al.. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 2013;31:1748–1757.
- 65.
Mitra A, Fisher C, Foster CS et al.. Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. Br J Cancer 2008;98:502–507.
- 66.
Narod SA, Neuhausen S, Vichodez G et al.. Rapid progression of prostate cancer in men with a BRCA2 mutation. Br J Cancer 2008;99:371–374.
- 67.
Thorne H, Willems AJ, Niedermayr E et al.. Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families. Cancer Prev Res (Phila) 2011;4:1002–1010.
- 68.↑
Tryggvadottir L, Vidarsdottir L, Thorgeirsson T et al.. Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst 2007;99:929–935.
- 70.↑
Bancroft EK, Page EC, Castro E et al.. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol 2014;66:489–499.
