2017 Latest Prostate Cancer Research: What to do for an Elevated PSA? The Classical Pathway for the Diagnosis of Prostate Cancer versus The State of the Art Pathway for Prostate Cancer

The Classical Pathway for the Diagnosis of Prostate Cancer is:
1. Check PSA: prostate-specific antigen
2. Get digital rectal examination (DRE) 
3. If PSA is elevated alone, get DRE.
4.  If PSA is elevate and/or a suspicious digital rectal examination (DRE), get 
Trans-Rectal Ultrasound Guided Biopsy (TRUS-GB) of the prostate. 
TRUS is performed to help guide the surgeon to the location of the prostate but ultrasound does not identify clinically significant cancer (CSC) with high accuracy. Biopsies are taken usually taken from the peripheral zone, which have the majority of cancers.
5. Depending on Results, patients would be monitored or treated for Prostate Cancer with:
a. Radiation
b. Chemotherapy

The State of the Art Pathway for Prostate Cancer

1. Check PSA and repeat the PSA test: prostate-specific antigen
2016 National Comprehensive Cancer Network
(NCCN) guidelines recommend repeating the PSA
test for confirmation as PSA values can fluctuate for various reasons, such as inflammation, infection,
benign prostate hyperplasia, medical instrumentation,
2. Get digital rectal examination (DRE) 
3. If PSA is elevated alone, get DRE.
4.  If PSA is elevate and/or a suspicious digital rectal examination (DRE), get 
State-of-the-art, full multiparametric contrast-enhanced MR imaging (at 3.0-T including high-spatial-resolution structural imaging in several planes, diffusion-weighted imaging at 0, 800, 1000, and 1400 mm2/sec, and dynamic contrast-enhanced MR imaging, obtained without endorectal coil within 34 minutes 19 seconds) after or Instead of Trans-Rectal Ultrasound Guided Biopsy (TRUS-GB) of the prostate: some researchers are arguing MRI shows where there is a possible cancer & the results of a biopsy after the MRI are better than with just an Ultrasound Guided method.  This is controversial to say the least. 
5. Get one or many of the below laboratory parameters that can be measured after confirming elevated PSA. These newer tests help determine your risk score.
a. Prostate Health Index (PHI) test
(Beckman Coulter, Inc., Brea, California, United States) 
This blood test assesses three PSA isoforms: free PSA (fPSA), total PSA, and ( 2)proPSA [52]. PHI is calculated using the formula: [( 2)proPSA/fPSA] PSA1/2 and is reported as a continuous variable. The output is the probability of finding Prostate Cancer on biopsy and the probability of aggressive disease. PHI testing is approved for men at least 50 years old with normal DRE results and PSA values within the gray zone of 4–10 ng/ml. A meta-analyses reported that PHI has higher diagnostic accuracy rates than other PSA derivatives and have utility in predicting aggressive Prostate Cancer.
b. Michigan prostate score (MiPS) 
(University of
Michigan MLabs) is a multiplex post-DRE urine
analysis of two PCa-specific genetic variants: the
US Food and Drug Administration (FDA)-approved
PCa Antigen 3 (PCA3) test and the TMPRSS2:ERG
gene fusion.
c. Urinary exosome gene expression assay: The ExoDx Prostate IntelliScore
Measures urinary exosomal RNA in first-catch urine samples without need for DRE. FDA approved. Studies showed urinary exosomes and standard of care variables (e.g., PSA, age) significantly improved the detection of high-grade disease on biopsy
d. The 4-kallikrein score 
The 4-kallikrein score (OPKO Lab, Miami, Florida, USA) is a simple blood test based upon 4-kallikrein markers:
1. total PSA, 
2. fPSA, 
3. intact PSA, 
4. human kallikreinrelated peptidase (hK2)
Similar to PHI, it has demonstrated better accuracy in predicting the incidence of Prostate Cancer than total PSA alone and in predicting high-grade disease (Gleason score 7 or greater).  
The 4-kallikrein score panel in the PSA gray zone (3–10 ng/ml) with or without prior PSA screening and with or without prior biopsy was examined in a recent meta-analysis and shown to be cost effective.  
The 4-kallikrein panel incorporates clinical variables (age, family history, and DRE findings) into its output. It has been reported to provide an 8–13% improvement in predictive accuracy and a potential 48–56% reduction in biopsies.
e. SelectMDx 
(MDxHealth, Irvine, California, USA) is
performed on a post-DRE urine sample and
measures the mRNA levels of the HOXC6 and
DLX1 biomarkers, using KLK3 expression as internal
reference standard

5. Depending on Results, patients would be monitored or treated for Prostate Cancer with below.
See last reference on a consensus by MDs around the world:
The panel unanimously agreed (100%) that apart from morphology and tumour stage, the following factors should be reported from a RP sample: (1) seminal vesicle involvement, (2) extraprostatic extension, (3) positive surgical margins (number, length and location, grade at margin), (4) Gleason score, and (5) grade group. There was also consensus that the following factors should be reported: (1) extent of prostatic involvement (96%), (2) number and anatomic region of resected lymph nodes and number and location of involved lymph nodes (94%), (3) tertiary Gleason grade (94%), and (4) micrometastases versus macrometastases in involved lymph nodes (81%), extranodal extension (81%), and metastatic deposits in perinodal fat tissue (79%;Table 2).
a. Radiation
b. Chemotherapy
c. Hormone therapy
d. Anti-angiogenesis treatment
e. An option but not recommended by most MDs: Diet: controversial: Gerson Diet. 
There was a consensus (84%) that a lymph node dissection should be performed in the majority of men with cN0 cM0 high-risk prostate cancer undergoing RP whereas 9% voted for a lymph node dissection in a minority of selected patients and 5% did not vote for a lymph node dissection.
Regarding the minimum number of lymph nodes to constitute an adequate dissection in the majority of men with cN0 cM0 high-risk prostate cancer 76% of the panellists voted for a minimum of ≥11 lymph nodes (49% for 11–19 lymph nodes and 27% for ≥20 lymph nodes); 15% of the panellists voted for five to 10 lymph nodes, 9% abstained.
Regarding the template of lymph node dissection in men with high-risk and locally advanced prostate cancer, there was a consensus that the obturator region (98%), internal iliac region (90%), and external iliac region (85%) should be dissected. Regarding the presacral lymph nodes, 51% of the panellists voted against and 46% in favour of dissection, similarly for common iliac lymph nodes 52% of the panellists voted against and 45% in favour of dissection. There was a consensus (95%) against routine dissection of para-aortic lymph nodes (Table 3).
Good review but from 2013:


Voigt JD, Zappala SM, Vaughan ED, Wein AJ. The Kallikrein Panel for prostate
cancer screening: its economic impact. Prostate 2014; 74:250–259.

 2017 Jun 12. doi: 10.1097/MOU.0000000000000418. [Epub ahead of print]

A multiparametric approach to improve upon existing prostate cancer screening and biopsy recommendations.



To provide an overview of how genetic, serum, and urine biomarkers can help identify men at high risk for prostate cancer (PCa) and aggressive disease and men who would benefit from prostate biopsy.


Screening for PCa is controversial because of concerns about overdiagnosis and overtreatment of nonlife-threatening tumors. Therefore, an approach to screening that includes a detailed family history with genetic testing of risk single nucleotide polymorphisms and high-penetrance genetic variants should be considered. After an elevated serum prostate-specific antigen (PSA) level has been confirmed, obtaining additional information (family history, biomarkers, and imaging) should be considered before recommending a prostate biopsy.


There are now genetic tests that can help identify men who would benefit from PSA testing. Additional biomarker and imaging tests should be offered to those men who are confirmed to have elevated PSA values. These new biomarkers and imaging tests can improve the specificity of PSA testing while missing a small percentage of high-grade tumors. The path forward involves a multiparametric risk assessment based on clinical data and these new tests.

 2015 Sep;1(2):99-108. doi: 10.1016/j.euf.2015.08.001. Epub 2015 Aug 28.

The Role of Biomarkers and Genetics in the Diagnosis of Prostate Cancer.



Given the pitfalls of prostate-specific antigen (PSA) testing for screening men with asymptomatic prostate cancer (PCa), a number of novel biomarkers have recently been studied that potentially decrease false-positive PSA results and unnecessary biopsies.


To review the literature on biomarkers with potential diagnostic utility for PCa by guiding the decision for initial or repeat biopsies in patients with elevated PSA.


We conducted a systematic literature review of human clinical studies on diagnostic biomarkers reporting clinicopathologic outcomes. A comprehensive search was performed in the Medline, Scopus, and Web of Science databases for articles from January 2005 through June 2015.


For men presenting with elevated PSA, especially in the 4-10 ng/ml range, who are considered for initial prostate biopsy, two serum-based assays, the Prostate Health Index and the four-kallikrein panel, can help identify patients with an increased risk of significant cancer on biopsy. In the setting of a prior negative biopsy but elevated PSA, urine-based assays detecting prostate cancer antigen 3 and/or transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog fusion transcript help predict the risk of high-grade cancer on subsequent biopsy. In cases with elevated PSA and an initial negative biopsy, epigenetic analysis can predict cancer diagnosis on subsequent biopsies. The combination of these novel biomarkers with existing nomograms and risk calculators leads to increased predictive accuracy and avoids unnecessary biopsies.


Rapid strides have been made in the discovery of novel biomarkers for guiding biopsy decisions in men suspected of harboring PCa. Although some of them have been approved for specific clinical settings, most of them still await rigorously designed prospective validation studies.


Novel urine-, serum-, and tissue-based biomarkers have been validated for guiding decisions on prostate biopsy in asymptomatic men with elevated prostate-specific antigen. Further exploration in this field may help expand their diagnostic and prognostic roles for prostate cancer.
 2017 Jul 20:170129. doi: 10.1148/radiol.2017170129. [Epub ahead of print]

Abbreviated Biparametric Prostate MR Imaging in Men with Elevated Prostate-specific Antigen.


Purpose To determine the diagnostic accuracy for clinically significant prostate cancer achieved with abbreviated biparametric prostate magnetic resonance (MR) imaging in comparison with full multiparametric contrast material-enhanced prostate MR imaging in men with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (US)-guided biopsy findings; to determine the significant cancer detection rate of biparametric versus full multiparametric contrast-enhanced MR imaging and between-reader agreement for interpretation of biparametric MR imaging. Materials and Methods In this institutional review board-approved retrospective review of prospectively acquired data, men with PSA greater than or equal to 3 ng/mL after negative transrectal US-guided biopsy findings underwent state-of-the-art, full multiparametric contrast-enhanced MR imaging at 3.0-T including high-spatial-resolution structural imaging in several planes, diffusion-weighted imaging at 0, 800, 1000, and 1400 mm2/sec, and dynamic contrast-enhanced MR imaging, obtained without endorectal coil within 34 minutes 19 seconds. One of four radiologists with different levels of expertise (1-9 years) first reviewed only a fraction of the full multiparametric contrast-enhanced MR images, consisting of single-plane (axial) structural imaging (T2-weighted turbo spin-echo and diffusion-weighted imaging), acquired within 8 minutes 45 seconds (referred to as biparametric MR imaging), and established a diagnosis according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2; only thereafter, the remaining full multiparametric contrast-enhanced MR images were read. Men with PI-RADS categories 3-5 underwent MR-guided targeted biopsy. Men with PI-RADS categories 1-2 remained in urologic follow-up for at least 2 years, with rebiopsy (transrectal US-guided or transperineal saturation) where appropriate. McNemar test was used to compare diagnostic accuracies. To investigate between-reader agreement, biparametric MR images of 100 patients were read independently by all three radiologists. Results A total of 542 men, aged 64.8 years ± 8.2 (median PSA, 7 ng/mL), were included. Biparametric MR imaging helped detect clinically significant prostate cancer in 138 men. Full multiparametric contrast-enhanced MR imaging allowed detection of one additional clinically significant prostate cancer (a stage pT2a, intermediate-risk cancer with a Gleason score of 3+4) and caused 11 additional false-positive diagnoses. Diagnostic accuracy for detection of clinically significant cancer of biparametric MR imaging (89.1%, 483 of 542) was similar to that of full multiparametric contrast-enhanced MR imaging (87.2%, 473 of 542). Between-reader agreement of biparametric MR imaging interpretation was substantial (κ = 0.81). Conclusion Biparametric MR imaging allows detection of clinically significant prostate cancer missed by transrectal US-guided biopsy. Biparametric prostate MR imaging takes less than 9 minutes examination time, works without contrast agent injection, and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MR imaging protocols. © RSNA, 2017.

Prostate Cancer Treatment Review:

 2017 Jun 24. pii: S0302-2838(17)30497-9. doi: 10.1016/j.eururo.2017.06.002. [Epub ahead of print]

Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017.

Author information

Department of Medical Oncology, Cantonal Hospital St. Gallen and University of Berne, Switzerland. Electronic address: silke.gillessen@kssg.ch.
Department of Medical Oncology, The Institute of Cancer Research/Royal Marsden, London, UK.
Oregon Health & Science University Knight Cancer Institute, OR, USA.
Department of Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Department of Radiation Oncology, Genito Urinary Oncology, Prostate Brachytherapy Unit, Goustave Roussy, Paris, France.
Department of Radiation Oncology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, USA.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, New York, NY, USA.
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Department of Urology, Gangnam Severance Hospital, Yonsei University Health System, Seoul, Korea.
Department of Urology, The Christie and Salford Royal Hospitals, Manchester, UK.
Department of Medical Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Monash University and Eastern Health, Eastern Health Clinical School, Box Hill, Australia.
Department of Urology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Department of Medical Oncology, Division of Haematology/Oncology, Columbia University Medical Center, New York, NY, USA.
Department of Clinical Oncology and Genetics, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
Department of Medical Oncology, University of Texas MD Anderson Cancer Center, TX, USA.
Department of Urology, University of California, Davis School of Medicine, CA, USA.
Department of Nuclear Medicine, Policlinico S. Orsola, Università di Bologna, Italy.
Department of Radiation Oncology, University of California, San Francisco, CA, USA.
Department of Medical Oncology, Gustave Roussy, University of Paris Sud, Paris, France.
Department of Surgery, Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University.
Department of Urology, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Department of Clinical trials and Statistics, Duke University, Durham, NC, USA.
Department of Urology, University Hospital Köln, Köln, Germany.
Department of Medicine, Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, WA, USA.
Department of Clinical Oncology, Clinical Oncology Queen Elizabeth Hospital Birmingham and University of Birmingham, Birmingham, UK.
Department of Medical Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Department of Clinical Oncology, Tampere University Hospital, Faculty of Medicine and Life Sciences, University of Tampere, Finland.
Department of Urology, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Urology, Medical University of Vienna, Vienna, Austria.
Department of Genitourinary Medical Oncology, MD Anderson Cancer Centre, Houston, TX, USA.
Department of Medical Oncology Hospital Israelita Albert Einstein and Department of Medical Oncology Beneficência Portuguesa de São Paulo.
Department of Medical Oncology and Epidemiology, Vanderbilt University Medical Center, Division of Hematology/Oncology, Nashville, TN, USA.
Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Urology, University Hospital Nord St. Etienne, St. Etienne, France.
Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India.
Department of Medical Oncology, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, The Tisch CancerInstitute, New York, NY, USA.
Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
Department of Radiology, Mount Vernon Cancer Centre and Institute of Cancer Research, London, UK.
Department of Clinical Oncology, Royal Marsden NHS Foundation Trust, Sutton, UK.
Department of Pathology, University of Washington, WA, USA.
Department of Pathology, University of Bern and the Inselspital, Bern (CH).
Department of Medical Oncology, Clinical Medicine and Urology at the Helen Diller Family Comprehensive Cancer Center at the University of, California, San Francisco, CA, USA.
Department of Urology, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada.
Department of Medical Oncology, Tulane Cancer Center, New Orleans, LA, USA.
Department of Medical Oncology, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Centre, New York, NY, USA.
Department of Medical Oncology, Department of Oncology, Assaf Harofeh Medical Centre, Tel-Aviv University, Sackler School of Medicine, Zerifin, Israel.
Department of Urology, Carolina Urologic Research Center, Myrtle Beach, SC, USA.
Department of Medical Oncology, Massachusetts General Hospital Cancer Centre, Boston, MA, USA.
Prostate Cancer Foundation, Santa Monica, CA, USA.
Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy.
Department of Urology, Toho University Sakura Medical Center, Japan.
Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Department of Medical Oncology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
Department of Urology, Cliniques Universitaires Saint Luc, Brussels, Belgium.
Department of Oncology and Haemato-oncology, Università degli Studi di Milano. Radiation Oncology 1, Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Radiation Oncology, Klinik für Strahlentherapie und Radioonkologie des Universitätsklinikum Ulm, Albert-Einstein-Allee, Ulm, Germany.
Department of Medical Oncology, Cantonal Hospital St. Gallen and University of Berne, Switzerland.



In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate CancerConsensus Conference (APCCC) 2017 addressed some of these topics.


To present the report of APCCC 2017.


Ten important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; “oligometastatic” prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions.


The panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process.


Voting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data.


The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them.


The second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process.
 2017 Jul 4. doi: 10.1159/000478789. [Epub ahead of print]

The Role of Radical Prostatectomy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.



The role of radical prostatectomy (RP) is still controversial for locally advanced prostate cancer (PC). Radiotherapy (RT) and hormonal therapy (HT) are usually used as a primary treatment.


A systematic online search was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Eligible publications reporting the overall survival (OS) and/or disease-specific survival (DSS) were included. A total of 14 studies, including 17,869 patients, were considered for analysis. The impact of therapeutic modalities on survival was assessed, with a risk of bias assessment according to the Newcastle Ottawa Scale.


For RP, RT, and HT, the mean 10-year OS was 70.7% (95% CI 61.3-80.2), 65.8% (95% CI 48.1-83.3), and 22.6% (95% CI 4.9-40.3; p = 0.001), respectively. The corresponding 10-year DSS was 84.1% (95% CI 75.1-93.2), 89.4% (95% CI 70.1-108.6), and 50.4% (95% CI 31.2-69.6; p = 0.0127), respectively. Among all treatment combinations, RP displayed significant improvement in OS when included in the treatment (Z = 4.01; p < 0.001). Adjuvant RT significantly improved DSS (Z = 2.7; p = 0.007). Combination of RT and HT favored better OS in comparison to monotherapy with RT or HT (Z = 3.61; p < 0.001).


Improved outcomes in advanced PC were detected for RP plus adjuvant RT vs. RP alone and RT plus adjuvant HT vs. RT alone with comparable survival results between both regimens. RP with adjuvant RT may present the modality of choice when HT is contraindicated.
Shopping Cart