Prostate cancer (PCa) is the most common male malignancy in our population. Over the past two decades, the prostate specific antigen (PSA) has been widely used for screening, diagnosis and monitoring of prostate cancer. Routine use of PSA has been continuing subject to controversy due to its limited specificity, which is derived from the fact that serum PSA levels are produced in a variety of non-neoplastic conditions.The shortcomings in sensitivity and specificity of PSA have promoted the search for new biomarkers to improve diagnostic performance. The ultimate goal is to get those diagnosing clinically significant prostate tumors and to individualize treatment in this disease.Among the biomarkers studied in prostate cancer we could found tissue biomarkers as well as serum or urine biomarkers. In this paper we proceed to review those serum biomarkers not related to PSA that have been published in the literature

In this narrative review we present the natural evolution of predictive models to their presentation in the nomogram format. We show their clinical usefulness and the objective parameters that contribute to their clinical use: calibration, discrimination, decision curves and probability density functions. We continue detailing the various existing predictive models/nomograms in relation to prostate cancer aggressiveness before and after biopsy, before and after primary treatment, recurrence and castration resistance. Finally we include future markers in advanced stage of implementation in the context of nomograms and related to the aggressiveness of prostate cancer: PCA3, PHI coefficient, 4Kscore, cell cycle progression (Prolaris®) and single nucleotid polymorphisms.

OBJECTIVE: To provide an updated state of the art about the role of positron emission tomography/computed tomography (PET/CT) with 11C-Choline and 18F-fluorocholine in the localized and locally advanced Prostate Cancer (PCa) in the staging and restaging setting.METHODS: We performed a non-systematic review of the literature based on a free-text search in the National Library of Medicine Database (MEDLINE) to select English-language published papers evaluating PET and Arch. Esp. Urol. 2015; 68 (3): 354-370PET/CT imaging with radiolabelled choline in initial diagnosis and in post-treatment phase in PCa patients.RESULTS: PET and PET/CT with 11C-choline and 18F-fluorocholine have been largely investigated as non-invasive diagnostic tools in PCa. Actually, the relatively high rate of false negative findings due to the small dimension of neoplastic lesions and the available spatial resolution of PET tracers limits the routine use of choline PET and PET/CT in staging setting; moreover, it cannot reliably replace the lymph node (LN) dissection for detecting LN involvement. On restaging setting, Choline PET/CT showed a higher accuracy than conventional imaging modalities, especially in the detection of LN and systemic metastases, while it is less accurate than magnetic resonance imaging in the detection of local relapse. CONCLUSION: In the Prostate Specific Antigen (PSA) era with a large number of localized disease, the diagnostic performance of choline PET and PET/CT lack of reliability in initial diagnosis of PCa. The major clinical role of choline PET/CT is the re-staging of patients with a biochemical relapse after radical treatment; the promising performance of choline PET/CT scan in patients with low levels of PSA could also lead the clinicians for to perform PET-guided adjuvant curative therapies or palliative treatments in patients already treated radically for PCa.

OBJECTIVES: The objective of this work is to evaluate the current role of conventional transrectal ultrasound guided biopsy of the prostate in the diagnosis of cancer. With this aim we review its indications, the various techniques, associated complications and limitations of this test.METHODS: We performed a bibliographic review through NCBI-PUBMED. We also evaluated the information and recommendations of the available clinical guidelines with their respective evidence levels. Lastly, some of the appraisals included are based on our group´s personal experience that has performed more than 7000 prostate biopsies with various protocols and methodologies over two decades of health care practice.RESULTS: Conventional prostatic biopsies lack precision; they are not close to reality in terms of tumor amount, localization and grading. The number and localization of the cores to be taken is not clear; there are too many biopsy schemes, making it less reliable and reproducible than expected. Although it is a good tool, there is an obvious risk of over diagnosis of clinically non-significant tumors. The lack of standardization of the various biopsy schemes has clear prognostic and decision-making implications. Another limitation is the scarce number of results attributable to biopsies targeted at ultrasound visible lesions. Obviously, the complications, discomfort, and distress generated by conventional biopsy and repeated biopsy programs are some of their limitations and the reasons for patient rejection. We are in a crossroad where multiple groups try to demonstrate the sensitivity and reproducibility of targeting the biopsy, by means of various techniques, to the lesions found in multiparametric MRI.CONCLUSIONS: Ultrasound guided prostatic biopsy is the main diagnostic method for prostate cancer yet. The information it gives is greatly relevant for staging, prognostic evaluation and therapeutic decision-making. Nevertheless, its limitations are evident: low sensitivity,overdiagnosis, complicacions, patient`s distress, etc. There are two lines of development to improve its efficiency. The one aiming to reduce the number of biopsies and cores by selectively targeting the findings of the MRI and the one that continues systematizing schemes with increasing number of cores to achieve the optimal sampling. Technical advances , such as image fusion, will maybe allow us in the future to translate the MRI findings into verified and reproducible clinical results. We must standardize the conventional techniques of prostate biopsy in our centers, using protocols and making them safe for patients. We must review our results to ensure reasonable detection rates, as well as our indications, considering patient´s age, comorbidities and expectations about therapy. We must include, as far as possible, other tools, such as multiparametric MRI to enable biopsy rationalization and improve their efficacy.

Prostate cancer (PCa) is still a main health issue, in fact it is responsible for 10% of cancer deaths across Europe. The morphology of the prostate gland makes urine an ideal sample, non invasive, for determi- nation both diagnostic and prognostic biomarkers. We use urinary PCA3 levels to indicate a prostate biopsy, and it is the only urinary biomarkers in PCa with FDA approval for clinical use. Many other biomarkers ba- sed on the expression of specific genes of PCa are be- ing studied and validated, for instance the fusion gene TMPRSS2-ERG with a commercial kit available, while another approach is to test the expression of a panel of genes. An emerging focus of research, which deserves attention, is miRNAs. Other newer approaches such as epigenetics, proteomics and metabolomics also would be very useful in the future for the development and va- lidation of new biomarkers. In this paper we review the state of the art in the field of urinary biomarkers in PCa.

The current diagnosis of prostate cancer is based on randomized prostate biopsies to obtain histological material for study, without introducing any imaging technique in the diagnostic algorithm.OBJECTIVES: To conduct a literature review of the role of multiparametric MRI ( mMRI ) in the diagnosis of prostate cancer, and present preliminary data from our series of 233 patients undergoing mRMN and transrectal ultrasound (TRUS) prostate biopsy.MATERIAL AND METHODS: We performed a PubMed search for those articles that refer to the usefulness of mMRI in the follow-up and monitoring of patients with persistently elevated PSA without previous biopsies, and those with a previous negative biopsy, and assess the power of mRMN for detecting PCa in both the peripheral and the central gland.We present the preliminary results of our series, consisting of 233 patients selected between 2008 and 2011 undergoing mMRI and TRUS-guided prostatic biopsy because of elevated PSA levels or suspicious digital rectal examination.RESULTS: We discuss several articles published from 2003 to 2014. We compare our results with those from the literature.DISCUSSION: The diagnostic algorithm of prostate cancer to date does not include any imaging technique in the decision-making process. The mMRI is a functional imaging technique that provides increasing evidence in deciding which patients should be biopsied and which patients may avoid it despite persisting high levels of PSA. The advantage of this technique lies not only in its high detection rate in intermediate and high risk lesions, but also in its high specificity. It allows us to avoid diagnosing clinically insignificant tumors and thus, avoids overtreatment.CONCLUSION: The mRMN is a useful technique not yet incorporated in algorithms of prostate cancer diagnosis in urological societies. Its safety, effectiveness and efficiency are forcing to include its progressive use and with high probability will be soon incorporated into the decision-making charts.

Prostate specific antigen has maintained a key role as serum marker for prostate cancer (PCa) diagnosis and management since almost 25 years ago. However, suboptimal sensitivity and specificity, resulting in missed diagnoses, unnecessary prostate biopsies, as well as, detection of clinically indolent disease emphasize the need for new biomarkers.OBJECTIVE: The purpose of this review is to examine the current status of tissue-based PCa markers, with special emphasis on recently marketed assays, and to evaluate their potential advantages to improve diagnosis, discriminate between indolent and aggressive disease, as well as, their role selecting therapeutic strategies.EVIDENC SYNTHESIS: PubMed-based available literature provided primarily the core for this review. The more recent, larger size series, meta-analysis and frequently referred originals were prioritized. Advances in genomics, molecular technologies along with new immunohistochemical procedures have enabled the discovery and study of a growing number of PCA markers. In the past two years, these efforts have produced assays to more accurately detect and characterize the disease. We present the development and validation of tissue-based genetic tests, and discuss the challenge of incorporating the use of these new markers into clinical practice.CONCLUSIONS: Since prostate cancer is a heterogeneous disease, having a defined set of markers for early diagnosis, prognosis and follow-up, is clinically relevant. Some of these new markers can now be used to complement the conventional histopathologic diagnosis, as well as, to help already established parameters assessing prognosis.

Prostate cancer (PCa) is a public health problem in western male populations on the basis of it´s high incidence and prevalence. Nowadays we come to changes in the diagnostic technologies that deserve special attention and that once applied allow to show the way towards a personalized view of PCa being able to join this modern current trend of the oncologic pathology.In spite of the recognized heterogeneity of the disease; clinical, pathological and genetic variants in genes and the limitations of the PSA as a biomarker to determine the biological aggressiveness of PCa, the certain thing is that the therapeutic final decision is adopted on the basis of a distant information to the wished customization and it moves excessive uncertainty for patients.In this respect the search based on the identification of alterations on the genomic sequence and it´s influence in the molecular characterization of the PCa is a constant in the investigation since nowadays.Actually, the progressive adjournment to the clinic of information tumour information that comes from the diagnostic tests related genetic material or their biochemical products, though still in initial phase, already allows to predict relevant changes in molecular characterization of the prostate cancer, in the eventual availability of predictive biomarkers from susceptibility to suffer the disease and of the personalized stratification of risk across the incorporation of newly and interesting molecular and immunohistochemistry biomarkers. Likewise the advances in the perspectives opened with the diagnosis, and the relevance in the decisions of biopsy indications that stem from it are based on the utilization, with the corresponding merger of images, of the multiparametric magnetic resonance (mpMRI) and the new prostate ecographic transrectal images with it´s natural evolution towards focal treatments represent, in spite of the recognized complex interpretation of the images, another significant transformation towards the individualization and ideally customization of the clinical decisions opposite to a certain patient with PCa. Events all of them, even more, if they are considered to be combined turn out to be very promising and it´s integration brings us over to personalized medicine in PCa since already it happens in others, though still small, neoplastic diseases.All this aspects are summarized and discussed in the present article in the light of the recent communicated informationand the reflection and personal experience of the authors. Finally chasing how to improve the clinical managing and the treatment for patients with PCa.

Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the diagnosis and modified the epidemiology of prostate cancer (PCa). Although it lacks of many characteristicsbof an ideal tumor marker, it is the marker most used for diagnosis and follow up of any kind of cancer. It re- presents the best clinical tool we have available today for screening and staging of PCa. On the contrary, its greatest limitation is the lack of tumor specificity. The use of PSA by-products and molecular isoforms tries to solve, at least partially, its limitations. Indeed, the use of FreePSA ratio (%fPSA) ad PSA density (PSAD) increase significantly the specificity of the diagnostic test and, the use of derivatives that evaluate time kinetics of PSA (PSA velocity (PSAV) and PSA doubling time (PSADT)) represents a very useful tool for prognosis estimation during treatment and follow up of the disease. The greatest advance over the last years comes from the analysis of the predecessor isoform (-2) pPSA and the phi Index. Both markers have demonstrated to improve the sensitivity and specificity results obtained to date, re- sulting in a decrease of unnecessary biopsies. Probably, with the ongoing development of new markers for PCa , the role of PSA on disease diagnosis and staging would be modified in a few years.

OBJECTIVES: Prostate biopsy (PB) is the gold standard for the diagnosis of prostate cancer (PCa). However, the optimal number of biopsy cores remains debatable. We sought to compare contemporary standard (10-12 cores) vs. saturation (≥18 cores) schemes on initial as well as repeat PB.METHODS: A non-systematic review of the literature was performed from 2000 through 2013. Studies of highest evidence (randomized controlled trials, prospective non-randomized studies, and retrospective reports of high quality) comparing standard vs saturation schemes on initial and repeat PB were evaluated. Outcome measures were overall PCa detection rate, detection rate of insignificant PCa, and procedure-associated morbidity.RESULTS: On initial PB, there is growing evidence that a saturation scheme is associated with a higher PCa detection rate compared to a standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40 cc), or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not uniform and differ among studies. Detection rates of insignificant PCa do not differ in a significant fashion between standard and saturation biopsies. On repeat PB, PCa detection rate is likewise higher with saturation protocols. Estimates of insignificant PCa vary widely due to differing definitions of insignificant disease. However, the rates of insignificant PCa appear to be comparable for the schemes in patients with only one prior negative biopsy, while saturation biopsy seems to detect more cases of insignificant PCa compared to standard biopsy in men with two or more prior negative biopsies. Very extensive sampling is associated with a high rate of acute urinary retention, whereas other severe adverse events, such as sepsis, appear not to occur more frequently with saturation schemes.DISCUSSION: Current evidence suggests that saturation schemes are associated with a higher PCa detection rate compared to standard ones on initial PB in men with lower PSA levels or larger prostates, and on repeat PB. Since most data are derived from retrospective studies, other endpoints such as detection rate of insignificant disease – especially on repeat PB – show broad variations throughout the literature and must, thus, be interpreted with caution. Future prospective controlled trials should be conducted to compare extended templates with newer techniques, such as image-guided sampling, in order to optimize PCa diagnostic strategy.

OBJECTIVE: The objective of this study isto review the evolution and changes of prostate cancerepidemiology and to perform an analysis of the currentstatus of prostate cancer screening based on the variousstudies and scientific societies recommendations.METHODS: We performed a bibliographic review ofrelevant papers in relation to prostate cancer epidemiologyand screening, with special focus on international andmulticentric trials on population screening.RESULTS: The current number and profile of patientsbeing diagnosed of prostate cancer have changed significantly from the pre-PSA era to the present time.Early diagnosis and screening strategies have causedan increase in incidence and a decrease in cancermortality in some countries.CONCLUSIONS: Systematic screening, despiteinconsistencies in some studies, seems to improveprostate cancer specific mortality. The introduction ofnew biomarkers, imaging techniques such as mpMRI aswell as less aggressive therapeutic alternatives, probablyopen windows to the future for a better diagnosis andtreatment of the disease

OBJECTIVES: Transrectal ultrasound-guided prostate biopsy remains the gold standard inthe diagnosis of prostate cancer. Various Ultrasoundmodalities have been proposed to increase the cancerdetection rate. Our purpose is to evaluate each of thesemethods , and to present its current literature and clinicalutility.METHOD: A non structured review of the current literaturewas conducted over these different various ultrasoundmodalities used during the transrectal ultrasound-guidedprostate biopsied in the diagnosis of prostate cancer.RESULTS: The data investigation of the various modalitiesassociated sonographic features exhibits greatheterogeneity and highly variable results. Some newtechniques sampling present promising results with highsensitivity and specificity, thus increasing the diagnosticyield of transrectal biopsy. It seems that elastographyshows encouraging figures, especially given the recentintroduction of the “shearvawe“ elastography thatdecreases the user-dependent factor.CONCLUSIONS: The ultrasound-guided prostate biopsyhas an acceptable sensitivity in the diagnosis of prostatecancer, but its specificity is still low. Various modalitiesassociated with ultrasound are available in clinicalpractice in order to increase cancer detection rate.Although some promising data have been publishedfor some of the modalities, we believe the combinationof these includes validated ultrasound guided biopsyprotocols to accurately target and diagnose prostatecancer

The current diagnosis of prostate cancer based on PSA values and systematic biopsy has limitations in its efficacy of detection and staging. Technical advances on imaging over the last decade, mainly MRI, enable improvements in the strategy of prostate cancer management in diagnosis, staging,follow up and therapy monitoring. MRI enables the combination of morphological (T2 sequences) and, at the same time, functional information by means of the application of sequences such as spectroscopy (SMRI), diffusion and dynamic intravenous contrast (CMRI) in the same study, giving the multiparametric MRI (mpMRI). Currently, it is not necessary to apply all sequences to obtain an mpMR study of optimal efficacy, so that a time shorter than 30 minutes is enough to obtain the necessary information depending on the clinical indication. The main clinical indications of prostatic MRI are a) local, regional or distance staging; b) Detection or guide for diagnostic biopsy for clinical risk suspicion or negative result in previous biopsies; c) active surveillance; and d) therapeutic monitoring. Furthermore, one of the most relevant features of prostate cancer, and a challenge for the mpMRI techniques is to be able to differentiate aggressive and non-significant neoplasias (latent). This update tries to review the current role of mpMRI in the management of prostate cancer using in combination the anatomical (T2) and functional (SMRI, DMRI and CMRI) information. We also describe the European prostate mpMRI guidelines, PI-RADS (Prostate imaging reporting data System)

Accuracy of multiparametric MRI has greatly improved the ability of localizing tumor foci of prostate cancer. This property can be used to perform a TRUS–MR image registration, new technological advance, which allows for an overlay of an MRI onto a TRUS image to target a prostate biopsy toward a suspicious area Three types of registration have been developed: cognitive-based, sensor-based, and organ-based registration. Cognitive registration consists of aiming a suspicious area during biopsy with the knowledge of the lesion location identified on multiparametric MRI. Sensor-based registration consists of tracking in real time the TRUS probe with a magnetic device, achieving a global positioning system which overlays in real-time prostate image on both modalities. Organ based registration does not aim to track the TRUS probe, but the prostate itself to compute in a 3D acquisition the TRUS prostate shape, allowing for a registration with the corresponding 3D MRI shape. The concept of an MR-US fusion TB strategy only is gaining more and more widespread acceptance. In a TB only strategy, fewer men could be biopsied overall, with a greater proportion of men diagnosed with clinically significant prostate, as well as fewer men“over diagnosed” with clinically insignificant cancer. However, more clinical research is required before this strategy is ready for widespread adoption.

Bone metastases are a recognized prognostic factor in patients with prostate cancer. Currently, Tc99 bone scan is the most frequently used imaging technique for their detection, showing a high sensitivity but a limited specificity. Thus, new morphological and mainly functional imaging techniques based on PET and MRI, or hybrid techniques such as PET-CT or PET-MRI have been introduced to improve metastases detection, estimation of total tumor load and for therapeutic monitoring. In this clinical scenario, total body MRI has arisen as a very promising technique in detection and therapeutic monitoring of bone metastases of prostate cancer, because it neither uses ionizing radiation nor needs the administration of contrast media. The incorporation of MR diffusion to the morphologic total body MRI protocols provides functional information, improving the sensitivity in oncological lesions detection in general and osteolytic bone metastases of PCa in particular. Its integration in protocols with morphological sequences and its quantification through ADC maps enables us to better understand metastatic bone disease patterns and their changes with different therapies. Total body D MRI enables the early classification of the response to treatment with evident advantages over other imaging techniques and the purely morphological approach with MRI. In any case, prospective and cost-effectiveness studies are necessary to establish the role of total-body D MRI in the management of patients with PCa.

Prostate cancer is one of the main health problems of the male population. Radical prostatectomy has demonstrated to have an excellent long-term cure rate. Nevertheless, globally, a 25% of the operated patients will suffer a PSA increase over 15 years offollow-up. Generally, the PSA value associated with a higher risk of clinical progression, that may be establishedas the cut point for biochemical recurrence is 0.4 ng/ml. Once biochemical recurrence is diagnosed, the most important clinical data is to determine if clinical recurrence is going to be local or systemic, because it will determine treatment. Main parameters helping to differentiate between one and another are: time interval to PSA increase, PSA velocity, PSA doubling time (PSADT), pathologic stage and specimen’s Gleason’s score. The possibilities of treatment of biochemical failure after radical prostatectomy are under debate. Nevertheless, it is currently considered that patients with biochemical recurrence without radiological evidence of distantmetastases are ideal candidates for local treatment with radiotherapy.

This review article presents the lateadvances in the pathologic diagnosis of prostate cancer, new concepts and predictive factors, emphasizing the new biomolecular markers in prostate cancer.

This paper presents a review of the concept of “nomogram” applied to prostate cancer, and specifically as a staging tool.METHODS/RESULTS: We describe the essentialparameters for the evaluation of such type of predictive models: Calibration, discrimination and clinical usefulness. Such requisites are analyzed using a real clinical case in our clinical setting, comparing the “Partin`s tables” and the “Miguel Servet University Hospital´s nomogram”. We demonstrate its correct calibration, discrimination and clinical usefulness after previous selection of proper cut points.CONCLUSION: The application of the predictivemodel to our clinical practice has achieved a clinical understaging of 17.3% after radical prostatectomy.

Currently prostate cancer is the mostfrequent extracutaneous neoplasia in males in the USA, and second after lung cancer in our country. Over the last years the profile of prostate cancers diagnosed has changed due to the wide diffusion of PSA determination. Currently, almost 47% of prostate cancers are low risk at diagnosis. In this situation, the minimally invasive therapiessuch as brachytherapy have a growing acceptance in our environment. We analyze the special PSA kinetics after brachytherapy, and the difficulty entailed by thediagnosis of biochemical recurrence after brachytherapy,performing a bibliographic review of the available scientific evidence.

OBJECTIVES: To evaluate if radicalprostatectomy may positively influence cancer-specific survival (CSS), hormone-resistance-free time, metastasis-free time, and quality of life(QoL) of patients with prostate adenocarcinoma and seminal vesicle invasion, and also to update our thoughts about seminal vesicle biopsy.METHODS: 114 patients were included. Forty-six cases were diagnosed of seminal vesicle invasion after radical prostatectomy; 68 cases were diagnosed of seminal vesicle invasion after biopsy, not undergoing then surgery. Cancer specific survival, time to hormone resistance from the start of hormonal treatment, metastasis free time and QoL, measured as need for hospital care, were compared between groups. Median follow-up time was 52.6 mos.RESULTS: There were not statistically significant differences between groups in CSS, time to hormone resistance, metastasis free time and QoL. Three and five-year cancer specific survival were 100% and 80.77% for the radical prostatectomy group and 74.4% and 56.2% for the biopsy group. Primary grade and Gleason Score were independent predictors for CSS in the Cox regression test; clinical stage was independent predictor for time to hormone resistance.CONCLUSIONS: Radical prostatectomy as monotherapy does not show a statistically significant influence onfollow-up time, CSS, time to hormone resistance, metastasis free time or QoL in patients with prostate cancer and seminal vesicle invasion associated with other bad prognostic factors (unfavourable Gleason and PSA). The value of seminal vesicle biopsy remains for the study of new multimodal treatments, such as chemotherapy + surgery, and it is to be defined in the planning of radio and cryosurgery.

The management of prostate cancerrepresents a real clinical problem for its unknown natural history, and unpredictable outcome and prognosis. The stage is the most important prognostic variable of any tumor. The use of nomograms, such as Partin`s tables, supplies important information for the evaluation of the local stage. Nevertheless, these methods have lowreliability because they do not use anatomical informationof the gland. The development of MRI techniquesincorporating high-resolution anatomical evaluation of the prostate in conjunction with metabolic information (MRI spectroscopy) offer the imaging technique of choice for the staging of prostate cancer in selected patients candidates to curative surgery. Prostate MRI offers the most reliable evaluation of local and regional staging. Anyway, many studies have described a wide variability in the reliability of prostate cancer staging by MRI,indicating that MRI is not a perfect imaging test because it cannot detect microscopic involvement. The objective of this article is to evaluate the current role of prostatic MRI for prostate cancer staging, evaluating its advantages,limitations and future expectations.

OBJECTIVES: To review the value of PSA kinetics in the diagnosis and prognosis of prostate cancer.METHODS: Review of the literature through a Medline search. CONCLUSIONS: A pre-tretament PSAV value >2ng/ml/yr is a risk factor for increased mortality from prostate cancer after surgery or radiation therapy. A PSADT 10 is more likely associated with local recurrence.

OBJETIVES: Ultrasound guided prostate biopsy is the only method to obtain the confirmation diagnosis of prostate cancer. Since its introduction at the end of the `80s multiple modifications of the technique have been implemented to improve cancer detection ratesand to diminish the rate of false negative results, with maximum patient comfort and less complications.METHODS: Bibliographic review and critical analysis of the literature on prostate biopsy.RESULTS/CONCLUSIONS: Published studies suggest extensive biopsy schemes increase detection rates in comparison to sextant biopsies, both first and successivebiopsies, being necessary to sample the most lateral areas of the gland and the dorsal apex where the diagnosticyield is greater. The indications for repeated biopsiesafter a negative one include high grade PIN and/orAtypical Small Acinar Proliferation (ASAP), persistent PSA elevation and/or total PSA doubling time increase. There is no consensus about the time for repeating biopsies, although it seems that cancer detection rates descend after the third biopsy. The introduction of periprostatic anesthetic blockage techniques has enabled pain control, mainly in more extensive biopsies.

Prostate cancer preferentially metastasizesto regional lymph nodes and bone. The incidence ofdissemination has been reduced over the last years mainly due to the compost use of PSA. For this reason, the indication of complementary diagnostic tests has evolved with the aim of improving the diagnostic yield. Some of these techniques are currently under evaluation and may contribute in the close future to change the study of dissemination in the clinical practice. CT scan or MRI are the standard imaging studies for lymph node dissemination, whereas bone scan continues to be the routine test for bone dissemination.

OBJECTIVES: The endorectal MR spectroscopic imaging (MRS) is a new imaging technique that allows a more accurate and reliable evaluation for the localization and staging of prostate cancer(PCa) than the solemorphological study offered by endorectal MR alone. The combination of endorectal MRI and MRS allows a simultaneous morphologic and metabolic study thatimproves the detection of PCa. Moreover, the technical improvements recently introduced in the spectroscopic study of the prostate have led to an increase of reliability in the detection of PCa.METHODS AND RESULTS: We present in this article the advantages this technique offers in the detection of PCa in patients at high risk, as well as in patients with progressive PSA rising and previous negative biopsies. It also seems to be useful in the study of biochemical recurrences of PSA in previously treated patients, and for the study of the central gland. We comment, as well, the chance to use this tool in the staging of PCa. Our group is actually working with MRS in the detection of PCa, in collaboration with AATRM (Agency of Evaluation ofmedical technology for medical research) and wepresent some recent results in the use of this technique.CONCLUSIONS: MRS is a non-invasive method that allows the detection of PCa in the peripheral gland with a greater reliability than endorectal MRI alone, in selectyed patients. It is also a good technique for the study of the central gland, in which the detection of PCa is difficult by morphological methods. So, RMS allows the evaluation of metabolic disorders in the whole prostatic gland and improves the overall accuracy in the detection of PCa, either in the central or peripheral gland.

OBJECTIVES: Due to the permanence of the prostate, PSA does not descend to undetectablelevels after radical radiotherapy the way it happens after radical prostatectomy. PSA as response parameter after radiotherapy or for the characterization of biochemical recurrence is very sensitive but not much specific. The positive predictive value for local or systemic clinicalrecurrence is low, so that the use of PSA alone for the indication of rescue therapies is open to debate. There are different definitions of biochemical recurrence after radiotherapy. To date, the most standardized definition was that of the American Society for Therapeutic Radiologyand Oncology (ASTRO) in 1996, but it was exclusive for patients treated with external beam radiotherapy as monotherapy. It was very sensitive to the follow-up time, but it was based on retrospective data, and its correlationwith clinical progression was suboptimal. With the aim of improving the definition of biochemical failure ASTRO reunited a new expert commission in 2005 that gave a new definition of biochemical failure more specific for clinical events and valid in the context of short-termandrogen deprivation or brachytherapy. The finalrecommendations were to consider biochemical recurrencea PSA increase of 2 ng/ml or greater over the nadir, or patients that have received rescue therapies. Prostate biopsy after radiotherapy is employed in patients with suspicion of exclusively local recurrence to direct them to rescue therapies. The criteria for the diagnosis of posttherapy carcinoma must be homogenized beforeestablishing this test as a routine in the evaluation of treatment response. Standard imaging techniques for the localization of clinical recurrences (99-technetium bone scan, CT scan and MRI) are not much sensitive and it is predictable that other diagnostic tests which have a metabolic character (such as PET with various tracers, MR spectroscopy) will be used for the study of biochemical recurrence after radiotherapy in the near future.

OBJECTIVES: Ultrasound guided biopsies are the mainstay in the diagnosis of prostate cancer. With the aim of improving diagnostic performancesdifferent protocols of prostate biopsy have been designed. The addition of vascular contrasts to the ultrasound allows for identification of hypervascular regions more likely to be cancer. The new ultrasound modalities enhance contrast signal and specifically differentiate its signal from the tissue reflections.METHOD: A non structured review of the literature was conducted on the utility of the different ultrasound modalities and types in targeting the biopsies of the prostate.RESULTS: There are four types of ultrasound guided biopsies of the prostate: ultrasound guided biopsy of hypoechoic nodes, systematic biopsy protocols, Doppler guided biopsy and Contrast Enhanced Doppler guided biopsy. In spite of the broad literature only few series possess a methodologically correct design related to the use of reference standards. The diagnostic performance of each one of the different types of biopsy varies widely. Sensitivity and specificity of ultrasound guided biopsy of hypoechoic nodes depends on the type of population included in the study but in general its positive predictive value is low. The protocols of systematic biopsy increase the sensitivity of the prostate biopsy but still specificity is low. The Doppler techniques offer a marginal benefit.Contrast Enhanced Doppler guided biopsies series have reported only a slightly increase in sensitivity and asignificant improvement of the odds risk for diagnostic of prostate cancer. New arising ultrasound modalities present with promising preliminary results.CONCLUSIONS: Ultrasound guided biopsy have an acceptable sensitivity in the diagnosis of prostate cancer, however specificity is overall low. Among the differentultrasound techniques only Contrast Enhanced Ultrasound improves significantly the diagnostic risk of the biopsy although the sensitivity remains quite stable. New specific contrast ultrasound techniques are currently underinvestigation.

OBJECTIVES: To evaluate the current role of PSA as a diagnostic method for prostate cancer, as well as to analyze possible new markers.METHODS: We perform a bibliographic review for PSA, and its molecular forms, as a marker to define the presence of prostate cancer. We review the factors related to PSA modifications, predictive models, or the current controversies about the usefulness of its cutpoint to define the risk of prostate cancer or the marker itself. We analyze possible new markers and the most interesting work lines in the development of new markers. We used MEDLINE for the bibliographic search.RESULTS: Available data confirm that PSA has a high sensitivity; although specificity is low, mainly in the ≤ 10 ng/ml range, it may be increased with the use of various molecular isoforms, ratios or predictive models. Nevertheless, it is true that despite such studies it is difficult to increase specificity, so biopsies are reduced. Currently we have new markers, some of them already marketed, others in development, which seem to improve the specificity of PSA (isoforms, use of molecular biology).CONCLUSIONS: PSA is still the standard marker for the diagnosis of prostate cancer. It is important to improve the specificity; therefore we need new predictive models or new isoforms that help us to do a better selection of candidates for biopsy. There are various promising research lines with new markers, but there is not ideal substitute for PSA yet.

Positron emission tomography (PET) is anon-invasive nuclear medicine technology which usesradiotracers and cameras slightly different from the onesused in other nuclear medicine tests. Most current indicationsare for oncological diseases; in nephrology-urology itsuse has been reduced because of the characteristics ofthe most commonly used radiotracer,18F-fluor deoxiglucose(18F-FDG, a glucose analogue), which is excreted bythe kidney, limiting the interpretation of the study in urologicmalignancies. Currently, 18F-choline is a promisingradiotracer for both staging and restaging, especially ifhybrid PET/CT scan devices are used. New radiotracerswill be needed in the evolution of PET to obtain informationabout more specific aspects of prostate carcinoma thatwill modify therapy and follow-up