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Prostate cancer (PCa) is the most com-mon non-skin malignancy among men world-wide. PCa incidence is higher among African American (AA) men in comparison to the white population. Men with a pre-vious history of PCa in first-line relatives carry also an increased risk for this disease. The incidence of PCa diminished in United States (US) since the publication in 2012 of US Preventive Service Task Force (USPSTF), in which PCa screening was bestowed with a grade D of recommendation. Nonetheless, locally advanced and metastatic disease rates increased notably. In 2018, the USPSTF drop back in their statement against PCa screening and recommended this to be a shared-deci-sion between men 55-69 years old and their physicians. A side-by-side evaluation methodology of the three trials included in USPSTF review was performed. The high intensity screening modality and the lower contamination rate in the control arm found in the ERSPC trial justify the earlier splitting in the cumulative mortality curves between the screening and control arm when contrasted with the CAP and PCLO trials presented. We aim to perform an objective and critical review of the current practice on prostate cancer screening, regarding its limitations and when the physician should offer a shared-decision pro-cess screening based on PSA. The controversy over PSA screening has not ended de-spite unequivocal evidence that it saves lives. Although the USPSTF’s 2017 new draft is a step in the right direc-tion, there is more progress to be made concerning the identification of patients harboring high-risk tumors and, consequently, die of PCa. PSA baseline may lead us to differentiate properly patients at high-risk from those under risk of overdiagnosis and overtreatment. It is well established that mpMRI has come to help us in the di-agnosis of PCa and in the identification of clinically sig-nificant tumors. Finally, studies ongoing on biomarkers may assist us to improve our understanding about this frequent malignancy.
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INTRODUCTION: Prostate cancer (PCa) diagnosis cornerstone has been prostate-specific anti-gen levels during the past decades, with a worrisome overdiagnosis and overtreatment of non-clinically signif-icant disease. These pitfalls have prompted the search for more accurate molecular and genetic tests such as genetic biomarkers. These new assays allow the testing of serum, urine, or prostatic tissue for molecular and ge-netic signs of prostate cancer, and provide information regarding both diagnosis and prognosis.OBJECTIVE: This review summarizes the latest informa-tion regarding PCa biomarkers, and is designed to as-sist urologists with ordering and interpreting these tests for different patients. EVIDENCE ACQUISITION: A PubMed-based literature search was conducted up to June 2018. We selected the most recent and relevant original articles, clinical tri-als and reviews that have provided relevant information to guide biomarker use. EVIDENCE SYNTHESIS: In this review, we discuss 11 commercially available biomarker assays. Results of clin-ical validation studies are presented. CONCLUSIONS: The use of genetic PCa biomarkers has a unique role in screening, diagnosis, surveillance, risk stratification and treatment for this disease. It is im-portant that providers be able to recommend the appro-priate test for each individual patient and circumstance within the disease. In the present time, no biomarker can be recommended over another, and large-scale and multi-institutional studies are required to validate the effi-cacy and cost utility of these new technologies.
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Prostate cancer (PCa) is a very heteroge-neous disease with unknown outcome at the time of first diagnosis. Multiple clinicopathological parameters and modern imaging approaches are currently used to de-tect PCa and to assess the necessity of early or delayed treatment according to the predicted aggressiveness of the tumor. Despite regular adjustments of predictive systems based on histopathological factors such as the Gleason grading system or based on prostate MRI such as the Prostate Imaging Reporting and Data System (PI-RADS) these tools for risk stratification of PCa patients still harbor significant limitations with regard to the accuracy of PCa outcome prediction. Therefore, great hopes have been placed on the use of biomolecular markers which might be more closely associated with the underlying biological characteristics of this tumor entity and able to predict the course of the disease better than clinical parameters. Such biomarkers are expected to serve as valuable tools not only to improve PCa diagnostics but also to enhance pre- and posttreatment risk stratification which could finally facilitate therapeutic decisions.In this review, current literature on genomic biomarkers used for PCa detection and early prediction of the tumor aggressiveness is examined. First, germline mutations and single nucleotide polymorphisms which might influ-ence PCa onset are discussed in relation to the useful-ness of targeted PCa screening approaches. Moreover, different urine- and tissue-based diagnostic tests assess-ing PCa-associated alterations on genetic, epigenetic and transcriptional level are reviewed. Most of these genomic biomarker assays were validated in large pa-tient cohorts and their potential clinical usability could be proven. They provide useful diagnostic information to facilitate decisions with regard to screen men at risk to develop PCa or to repeat diagnostics in men with negative biopsy results, but persistent suspicion of can-cer. Several assays can assist the early identification of patients with high-risk PCa, who potentially would need treatment, and may facilitate the selection of patients suit-able for active surveillance. More evidence of the clini-cal usability of such genomic PCa detection assays has to be provided by further prospective studies to support the transferability of these new diagnostic approaches to daily clinical practice.
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Although pathology is the gold standard for confirming the diagnosis of prostate cancer (PCa), several marker for diagnosis may be useful and will help in doubtful cases to confirm the diagnosis of PCa. Ther-fore it is important to spread the knowledge of immuno-marker, in order to improve the clinicians understanding of stains and their usefulness.Like in other organs, clinicians and pathologists would like not to rely only on pathological criteria such as PSA, Gleason score, tumor size and pT stage, but also on tumor stains, permitting to predict prognosis and patients outcome, especially in patients with intermediate risk. Many markers have been proposed, but none is at the very moment approuved for current use.
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There is yet no international consensus on the role of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer diagnosis, with different uses in different health care systems around the world. In this report we will discuss the use of mpMRI in the Uni-ted Kingdom, Europe and in the United States of Ameri-ca, comparing the most important guidelines and major papers over the last few years.
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OBJECTIVES: Prostate cancer diagnosis is undergoing a significant change in recent years. The concern about prostate cancer overtreatment as well as technological developments that allow for better visuali-zation of prostate cancer lesions are the main drivers for this change.METHODS: This was a narrative review of the literature on prostate cancer diagnosis.RESULTS: The diagnostic pathway of prostate cancer based on PSA screening and systematic TRUS has re-mained unaltered for many years. This is not free of error and many men with insignificant prostate cancer will be diagnosed. Secondly, men with significant prostate cancer will be missed. Moreover, TRUS approach is associated with a non-negligible rate of sepsis. With the introduction of prostate multiparametric MRI, it seems that we are moving towards a less invasive method of triaging men for prostate biopsy and adopting a biopsy technique which aims to target specific areas within the prostate rather than randomly sampling it. There are a number of other imaging modalities that have attrac-ted attention such as Elastography, histoscanning and contrast enhanced ultrasound. A targeted-only biopsy approach is a feasible option for prostate cancer diag-nosis that can improve significant cancer detection and reduce insignificant cancer detection when compared to TRUS biopsy.CONCLUSION: The introduction of multiparametric prostate MRI has the potential to change the way that we diagnose men with prostate cancer.
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The major goal of prostate cancer imag-ing in the next decade will be more accurate disease di-agnostic, characterization and staging through the syn-thesis of anatomic, functional and molecular imaging. Changes are happening regarding the use of prostate MRI for evaluating primary prostate cancer and PET CT for the staging and recurrence staging of prostate can-cer. This review presents a multidisciplinary perspective of the role of prostate MRI and molecular imaging in prostate cancer.
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OBJECTIVES: Active Surveillance (AS) has become an established treatment option for men with low-risk prostate cancer (PCa), demonstrating superior functional outcomes and excellent oncologic outcomes. As such, it has been appealing to extend AS to patients with intermediate risk PCa. We provide a review of the current experience with AS in the intermediate-risk PCa population.METHODS: Risk stratification is the key to treatment suc-cess. Many clinical factors (age, percent Gleason 4, PSA density, race/ethnicity, and genetic predisposition) and genomic markers have proven prognostic value in the AS population. We performed a systematic review of the currently available data (randomized trials and prospective cohort studies) to establish the status of AS in the intermediate risk patient population. RESULTS: Our ability to predict the natural history of in-termediate risk prostate cancer is imperfect. While the benefits of AS make it an appealing option for men with intermediate risk disease, the published experience to-date demonstrates that AS for all men with intermediate risk disease leads to higher rates of metastatic disease and loss of the opportunity for cure. These same studies also demonstrate that a subset of patients with intermedi-ate risk disease have indolent disease that may benefit from AS. This heterogeneity is not adequately captured with traditional histopathologic staging. Clinical, ge-nomic, and radiologic biomarkers play a key role in appropriate risk stratification and patient selection. The optimal use of these biomarkers in the intermediate risk patient is currently the subject of intense evaluation. CONCLUSION: Active surveillance for men at the fa-vorable end of intermediate risk prostate cancer is an appealing alternative to radical therapy, but carries a modest but increased risk of metastatic disease com-pared to low risk cancer. Many biomarkers are currently being evaluated to enhance precise risk stratification of this important subgroup of patients.
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INTRODUCTION: Focal therapy (FT) is a treatment option for prostate cancer (PCa), which offers the possibility of an effective therapy in selected patients who have the localized disease, with a significant re-duction in treatment related morbidity. Based on the cur-rent status of FT, our objective was to determine the most appropriate strategy to improve patient management. MATERIALS AND METHODS: A literature review was done performed through the PubMed database and fo-cused on the following topics: localised prostate cancer, MRI, prostate biopsies, ablative therapy and focal ther-apy. RESULTS: Indications for FT were mainly patients with a localised PCa, a single lesion at Gleason score 7 (3+4) (Grade group 2) favourable in size. Precise identifica-tion of the tumour, currently based on multiparametric MRI data and targeted biopsy, was the cornerstone of FT success. New imaging modalities such as PET/MRI and multiparametric ultrasound have proven to be effec-tive in detecting and targeting the tumour. Several ener-gy sources were reported for an effective tissue ablation. Non-thermal option should be investigated to further limit the risk of side effects with the same cancer control.CONCLUSION: Focal therapy is a new option in the armamentarium of PCa. Technological improvements and the development of novel energy sources should make it possible to treat lesions with even greater preci-sion, while limiting the risk of side effects. In the future, we should probably be able to effectively expand the indications of this technique to include more aggressive tumours.
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INTRODUCTION: Prostate cancer is the most common solid organ malignancy in men. Despite the implementation of PSA screening, the incidence of metastatic prostate cancer in Spain is still around 4%. In this clinical scenario, systemic treatment is the gold stan-dard. Cytoreductive surgery is a standard approach for some solid organ metastatic tumours. Recently there is interest in exploring the clinical benefit of local treatment (LT) to the primary site in oligometastatic prostate cancer.MATERIALS AND METHODS: Review of the relevant lit-erature to evaluate the benefit of local treatment (LT) in metastatic prostate cancer.RESULTS: Local treatment of the primary tumour has demonstrated oncological and symptomatic benefit in other malignancies. Multimodal therapies have demon-strated oncological and symptomatic benefit in locally advanced prostate cancer. Furthermore, surgery has been shown to reduce symptomatic progression in meta-static prostate cancer.CONCLUSION: The role of surgery to the primary site or metastasis directed treatment is currently being inves-tigated, in the context of oligometastatic prostate can-cer. Retrospective data provide a rationale for ongoing randomized controlled trials in this area. New imaging modalities might have a great impact in this conceptual change. Further data is still needed to recommend this approach as a standard of care.
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Oligometastatic prostate cancer (PCA) has increasingly been detected in the era of modern imag-ing studies such as choline-specific and prostate-specific membrane antigen (PSMA)-positron emission tomogra-phy and X-ray computed tomography (PET/CT). Recent evidence suggests that durable control is attainable with local treatment modalities such as salvage metastasec-tomy or stereotactic radiation therapy targeting oligome-tastases, either with or without the use of systemic ther-apy. The purpose of this article is to critically review the current findings on the indication, extent, and oncologic outcome of salvage lymphadenectomy (SLND).Oligometastatic PCA is defined by three or less to five metastatic lesions, no rapid spread to more sites, and feasibility of targeted treatment of all metastatic lesions with surgery or radiation therapy. 68Ga-PSMAPET/CT or 18C-choline PET/CT represents the imaging study of choice to identify patients with potential lymph node metastases, and both studies should be performed at prostate-specific antigen serum levels around 1 ng/ml in order to achieve optimal results. If available, 68Ga-PS-MA-PET/CT should be preferred because of higher sen-sitivity, specificity, and accuracy. With regard to pelvic SLND, only data of retrospective studies with a total of more than 400 patients and an evidence level III–IV are available. SLND should always be performed in terms of an extended lymph node dissection. Five-year biochem-ical free survival ranges between 19 and 25%, 5-year cancer-specific survival varies between 75 and 90%.The median time to systemic treatment is in the range of 20–30 months. Patients with retroperitoneal metastases have a poorer prognosis with less than 10% respond-ing. Optimnal candidates for SLND resulting in a good long-term control could be identified by integrating the following parameters in the clinical decision makong process: presence of Gleason pattern 5, PSA at time of SLND, > positive PSMA-PET/CT signals in the small pel-vis, presence of retroperitoneal lymph node metastases, pre-treatment with androgen deprivation therapy at time of biochemical relapse following radical prostatectomy.
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OBJECTIVES: Recent landmark studies (GETUG-AFU 15, CHAARTED, STAMPEDE (docetaxel), LATITUDE and STAMPEDE (abiraterone)) have changed the treatment of hormone sensitive metastatic prostate cancer (mHSPC) from androgen deprivation therapy (ADT) only to combined therapy with either docetaxel or abiraterone acetate plus prednisone (AAP) together with ADT. In this Review we highlight current evidence and recommendations on how to treat men with newly diagnosed mHSPC beyond ADTMETHODS: Narrative overview of available evidence retrieved from pubmed searches, hand searches and authoritative texts.RESULTS: Docetaxel or AAP in combination with ADT improves overall survival (OS) in men fit for combined treatment presenting with newly diagnosed mHSPC. The strongest evidence is for men with high volume mHSPC (four or more bone metastases with at least one outside the axial skeleton and/or visceral metastases) or mHSPC with high risk features (A minimum of two out of three following high-risk features: Gleason score ≥ 8, ≥ 3 bone lesions or visceral metastasis) as per CHAARTED and LATITUDE criteria, respectively. While upfront docetaxel and AAP yield comparable OS improvement, docetaxel has not been shown to increase OS specifically for men with low volume/low risk mHSPC, whereas, a recent post-hoc analysis from the STAMPEDE (abiraterone) trial showed consistent overall survival benefit of AAP plus ADT independent of risk stratification. While these data are limited by their retrospective nature, they do suggest that patients with low-risk mHSPC should be of-fered AAP. In men with high volume/high risk mHSPC, choosing between six-cycles of docetaxel or AAP until disease progression relies on patient preference, cost and individual assessment of which drug side-effect pro-file is most suitable. CONCLUSION: Offer men presenting with newly diag-nosed mHSPC fit enough for combined therapy either ADT plus docetaxel or AAP.
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There are multiple definitions of high risk prostate cancer and each definition is associated with a different prognosis. Men classified as having high-risk disease warrant treatment because durable outcomes can be achieved. Radical prostatectomy, radiation therapy and androgen deprivation therapy play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease.
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Prostate cancer (PCa) is the second most commonly diagnosed cancer. Although systemic chemo-therapeutic agents, such as cabazitaxel, abiraterone and enzalutamde have become available to patients over the last decade, metastatic PCa is still an incur-able disease. Immunotherapy is showing great promise in a wide range of other cancer types. To this day, the only immunotherapy approved by the FDA for PCa is the Sipuleucel-T vaccine, which showed significant clinical efficacy. Multiple clinical studies on immunotherapy in PCa are currently underway. OBJECTIVES: Recent clinical trials have shown promis-ing results in immunotherapeutic in treatment for PCa. The authors review previous clinical trials, as well as discuss and emphasize important emerging immunother-apies for PCa. METHODS: Review of the published evidence related to immunotherapy in PCa. PubMed and clinicaltrials.gov databases were used to search for English papers and clinical trials. RESULTS: Multiple clinical trials are testing different im-munotherapeutic agents, as well as combinations there-of. The low grade of toxicity associated with these im-munotherapies is an appealing advantage for patients, leading to an increased appreciation of theses types of treatments. Until now, only one clinical trial led to a new immunotherapeutic agent to be FDA approved. Import-ant phase II/III clinical trials are being conducted, and in the near future the concept of PCa treatment might be re-challenged. CONCLUSIONS: Many trials are ongoing to determine the effects of immunotherapy in PCa. These studies may harvest important confirmatory data in the next years, with the potential to reshape PCa treatment.
