OBJECTIVES: Active treatment in localized prostate cancer, in its various types, is assumed as a valid alternative. The effect of the possible overtreatment has raised that options such as active surveillance are offered as an alternative to active treatments, without evidence about its validity in many points. The objective of this study is to analyze the current controversies to define candidates to this alternative, follow up criteria, impact on quality of life and evidence bases to do it.METHODS: We perform an analysis updating the Medline search with the terms localized prostate cancer and active surveillance, analyzing the articles and their evidence, as well as guidelines recommendations.RESULTS: Selection criteria for candidates to active surveillance are heterogeneous, without evidence of uniformity. Likewise, follow up and its criteria or progression are not well defined. The impact on progression, or delay in decision-making, have not been analyzed and we lack of studies of highest evidence including comparative studies for cancer specific or global survival results.CONCLUSIONS: Although AS seems to be a reasonable alternative in many patients with localized prostate cancer, we still need to define many features of inclusion and decision-making. Comparative studies are needed to better define selection and validity of active surveillance.

OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the use of different inclusion criteria in an active surveillance (AS) program. This chapter presents the pathology findings of radical prostatectomy (RP) in patients whose disease meet criteria for AS, as well as of those who are operated during AS.METHODS: Two independent Medline searches were conducted, both of them with a double objective: pathological findingsin radical prostatectomy specimens of patients who could have been included in AS and pathological features of patients operated after an AS period. The following terms were used for the research: “prostaticneoplasm”, “radical prostatectomy” and “active surveillance”;: “radical prostatectomy”, “after”, “following” and “active surveillance”. Pathological findings in radical prostatectomy specimens, down staging and downgrading rates were recorded. Active surveillance length and reason for surgery was included when it was available.RESULTS: Depending on different AS inclusion criteria, clinical downgrading rate (pathological Gleason>6) varied between 12.1 and 61% and clinical downstaging between 0-26%. Pathological Gleason score ≥8 was reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion or positive nodes. Overall, unfavorable pathology (Gleason ≥7 or stage ≥pT3)was detected in 13.1 -42.4%, based on different definitions. The criteria at John Hopkins were the strictest and had the lowest clinical downgrading and downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center(MSKCC) criteria had the highest risk of unfavorable pathology but had the highest recruitment capacity. Indolent tumor was observed in 70-82.2% according to the current definition. The average duration in AS prior to surgery was 15-37 months. pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score 4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%. Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive nodes (0-4.5%).CONCLUSIONS: Although there is a low risk of clinical downstaging and downgrading between patients who have being included in AS, it remains feasible. The probability of predicting an indolent tumor depends greatly on the quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand, most patients who progress in an AS program can have a high probability of cure. We are still in the early stages of AS management in order to be able to predict the biological behavior and the cure rate of radical prostatectomy in patients after a long AS period.

OBJECTIVES: To review the pathological criteria used to select patients for active surveillance, the optimization of biopsies and the role of confirmatory biopsy and of the transperineal approach.METHODS: A bibliographic revision of the last years about active surveillance in prostate cancer as well as prostate biopsy, optimal rebiopsy protocols and transperineal approach has been carried out. RESULTS: Misclassification of insignificant disease based on pathological criteria of the first standard biopsy range from 20% to 30% of men. It is likely that many patients who ultimately progress on active surveillance had at the time of diagnosis more advanced disease that was missed by transrectal ultrasound (TRUS) biopsy. This is the main cause of progression on initial followup biopsy within 1 year of starting active surveillance. Although the role of immediate prostate rebiopsy after the diagnosis of low-risk prostate cancer and has not been well described, repeat biopsy before the initiation of AS performed shortly after diagnosis (6 months) identifies most patients who harbor high grade or more extensive cancers that may not be appropriate for a surveillance strategy. CONCLUSIONS: PSA, PSAD, and number of cores at initial diagnosis are not helpful in predicting misclassification of AS eligibility. The role of MRI for AS remains unclear and the technique of MRI/US fusion biopsy still lacks consensus on a standardized procedure. Patients considering active surveillance should undergo immediate confirmatory biopsy within 6 months to decrease the risk of substantially underestimating cancer size and grade, even in patients with strict criteria in the initial biopsy and subsequently, to better assess the risk of progression. In this way, most protocols of AS recommend performing volume-based biopsies in the confirmatory procedure. Perhaps, an extensive transperineal template-guided mapping biopsy (TTMB) procedure could more accurately identify those men with occult significant disease. Due to confirmatory biopsy identifies a patient group that is unlikely to progress during the first 5 to 10 years of AS the need of intensive biopsy schedule during follow-up of patients undergoing active surveillance might be reduced.

OBJECTIVES: The aim of this study is to provide an evidence-based analysis of the epidemiological situation of prostate cancer today and its future perspectives.METHOD: A literature review on Medline has been made of the most relevant papers related to the epidemiology of prostate cancer and their etiological factors. We selected for review those manuscripts with the highest level of evidence.RESULTS: Prostate cancer is the second most common neoplasia in men worldwide. The increasing trend in the incidente counteracted by an overall decrease in mortality from this disease have made prostate cancer an important health problem because of its high prevalence. There are significant geographic differences in terms of incidence and mortality.Age, ethnicity and family history are risk factors demonstrated but there are other factors related to the environment that play an important role in the biology of prostate cancer and tumor genesis.CONCLUSIONS: In the last 20 years there has been a progressive increase in the global incidence of this disease probably secondary to a progressive aging population, the improvement in diagnostic techniques and a higher intensity screening of prostate cancer. Though mortality has been reduced prostate cancer is the sixth cause of cancer-specific death worldwide.The combination of genetic and environmental factors may explain the ethnic and geographical variations in the incidence and mortality from prostate cancer.

- In the present review we detail the more universally accepted selection criteria in the various protocols of active surveillance in prostate cancer; we also identify and classify twenty nomograms/predictive models useful for decision making in active surveillance for prostate cancer.These models are classified in accordance to their prediction (High grade prostate cancer in radical prostatectomy specimen [Gleason grade > 7], understaging on biopsy compared to prostatectomy specimen, pathological stage, indolent cancer or progression after expectant therapy).We also detail the predictive variables used in each model for estimations, their internal validation parameters, the samples used to generate them, and the external validations if they were done. Many of them are presented with their URL address, where they may be consulted on line, this making easier their implementation.Finally we expose our thoughts about the use of probability density functions as a useful tool for validation of these predictive models that help in the definition of cut points facilitating their clinical use and credibility.

Thanks to the higher diagnostic accuracy and safety, new imaging techniques provide future prospects in terms of patient management and follow-up in active surveillance (AS) protocols.Two of the aims of developing new imaging techniques are improving patient selection criteria and to improve follow-up with non-invasive tests. Another objective is to improve the diagnostic performance of biopsies; this would enable physicians to switch from blind systematic TRUS-guided biopsies to targeted biopsies to reduce the amount of biopsies required and reduce the diagnostic rate of clinically insignificant cancers. The notable advances of multi-parametric or functional prostatic imaging (mpMRI) have led to perceptible diagnostic improvements as it they does do not only provide information regarding size and location but also tumor aggressiveness. MRI has proven to be the most reliable non-invasive technique to be able to exclude patients with clinically significant cancer and thus gain acceptance in AS protocols during selection, confirmation and follow-up of AS patients.This chapter reviews the notable impact of multiparametric prostate MRI (mpMRI) on improving both diagnostic accuracy and follow-up. The second point describes the technical advances in the field of transrectal ultrasound imaging, aiming at improving the diagnostic accuracy of biopsies given their increased accessibility and realtime use.

INTRODUCTION: Serum PSA determination has provoked a great increase of prostatic biopsies and detection of neoplasias that passed inadvertent in the past. When these neoplasias are excised a nonnegligible number of them have low biologic aggressiveness and may be considered as indolent or clinically non-significant, so that the possibility of conservative attitude is taken into consideration.OBJECTIVE: How to recognize clinically non-significant carcinomas is one of the main challenges and is based on clinical criteria, but mainly pathological. The objective of this review is to analyze the state of this issue.METHODS: We selected those articles reviewing the topic in a general view over the last ten years.RESULTS/CONCLUSIONS: Trying to be as specific as possible search criteria have been refined to Gleason grade with an increase of Gleason 4 patterns (all cribiform patterns). In cases with two separated foci of carcinoma in the same biopsy core, it has been proposed to include as neoplasia the non-tumoral tissue between them. Obviously, with this there is lower sensitivity and it entails that there is no unanimous agreement (or consensus) about how to establish the criteria of clinically non-significant carcinoma.Therefore, once again, it is completely mandatory that urologists and pathologists work together, and while no consensus is reached both must know perfectly the guidelines of the center they work in.

Prostatic cancer can be a silent tumor,with no symptoms remaining undetectable throughoutlife . But when it keeps growing, enough to producesymptoms such as bladder neck obstruction , invasion ofadjacent organs or distant metastasis, curative treatmentis usually impossible.Since PSA emerges, data shows a dramatic increasingin the diagnosis of prostatic cancer, specially low risktumor. Since then, We are wondering which tumorsare suitable to be treated and which ones remainasymptomatic without treatment. Analysing the naturalhistory of prostate cancer, helps us to choose the bestatitude treating the tumor, this subjet has been in constantdiscusión in the last decade. Our article consistes of areviewing the main publications treating natural historyof prostate cancer in pre-and post- PSA era.The indicated studied suggest that most prostate tumorsdiagnosed today are low grade cancer, as a result witha low mortality. This conclusión shows us the importanceof modifying the algorithm of treatment of these tumors

Prostate cancer screening is an absolutely controversial topic and under debate. The points of view from which the problem is analyzed also influence this issue; patient, physician and Health Care authorities have different interests that most of the times are not comprehensively analyzed. Currently, no clinical guideline supports the performance of a population screening with active recruitment, but they do support the credible information to the man who desires its performance of potential benefits and risks (opportunistic screening), as well as its performance in certain risk groups. Nevertheless, what is inherent to any screening program is the overdiagnosis of clinically irrelevant disease, which in prostate cancer has been calculated around 50%, and that, from our point of view, gives cause to the correct implementation of active surveillance programs to tamponade the potential deleterious effects of active therapies of prostate cancer.

OBJECTIVES: Prostate cancer is a highly prevalent disease but with reduced cause-specific mortality. Active surveillance represents an alternative to postpone or avoid the potential sequelae derived from curative treatments in selected patients.The objective of this article is to review the diagnostic and follow-up methods for patients included in active surveillance programs.METHODS: We performed an exhaustive bibliographic review with the terms “Prostate cancer”, “Active surveillance”, “expectant management”, including the greatest series published since 2007.CONCLUSIONS: Awaiting for genetic markers that help us to predict diagnosis and evolution of prostate cancer, PSA kinetics, digital rectal examination and repeated biopsies continue being the inclusion and follow up criteria for patients in active surveillance programs. Emerging complementary tests such as multi parametric MRI, PCA3 and Phi seem to add specificity to the existing clinical criteria. The reduced number of patients included, the limited follow up and the great disparity of inclusion and follow up criteria between different groups make the implementation of consensus guidelines that could help a more widespread application of this alternative difficult.

Identification of biomarkers that, at the time of diagnosis of prostate cancer (PCa) , are associated with presence of disease or a more aggressive behavior will transform the clinical management of this disease. If both patients and clinicians would have re- producible and valid tools to estimate the specific risk of morbidity associated with PCa, then many patients would opt to and join active surveillance (AS) protocols, and consequently costs and comorbidities associated with the current overtreatment of prostate cancer would be reduced. Thus, a biomarker, or a panel of biomarkers, with high specificity to identify patients at risk for progression in AS protocols, would identify those men who could benefit from less intensive AS protocols with less repeated biopsies, so reducing the risk and cost of these invasive procedures. In this review we try to offer an overview of the new markers identified by genomic techniques and to discuss their potential role in an AS context. Moreover, the AS protocol offers an adequate setting for validation of biomarkers associated to disease progression.

Active surveillance (AS) as a therapeutic option is already integrated as a primary treatment strategy in low risk localized prostate cancer (PCa). There is a recent interest for the search of therapeutic interventions that result in a delay in the progression of such indolent cancers. The evaluation of the possible implication of 5 ARI drugs in the reduction of the risk of progression of PCa was enacted by the results of the clinical trials PCPT (Prostate Cancer Prevention Trial) and REDUCE (Reduction by Dutasteride of Prostate Cancer Events study). The results of the REDEEM clinical trial (Reduction by Dutasteride of clinical progression events in expectant management trial)revealed a delay in PCa progression favoring Dutasteride in comparison with placebo, being advanced age and PSA Density independent predictive factors for pathologic progression. Evidences regarding the influence of 5 ARIs in the evolution of AS patients come from few studies with limited follow up. Thus, the conclusions probably are far from being consiidered as definitive.

In this article we review the most signifi-cant published papers on active surveillance in prostate cancer and present the results of our case series. We used as main response variables the percentage of patients remaining in surveillance and the oncological results presented as global, cancer specific and metastasis free survivals. Globally, in published series 71.2% of patients included in active surveillance programs, 10-year overall survival is 68% in the series with longer follow up, and cancerspecific survival varies from 97% to 100%.In our series of 144 patients with median follow up of 3.2 years, 76.3% of the patients continue on surveillance. 24 patients (15.9%) stopped surveillance due to histological progression.5 patients (21.3%) out of the 23 undergoing surgery presented unfavorable pathological criteria on prostatectomy specimen. No patient has died or developed metastases.

In a context where there is evidence that not every patient with low risk prostate cancer needs to be treated from the start, active treatments are expensive and public health care systems need to save money, studies on cost-effectiveness are a priority.To elaborate this article, we reviewed the publications on cost and cost-effectiveness of localized prostate cancer treatments that include active surveillance.In patients with low risk localized prostate cancer active surveillance is more cost-effective than active treatment. With time active surveillance may be more expensive than brachytherapy or radical prostatectomy. The frequency of prostatic biopsies and the percentage of conversions to active treatment will be determinant in final costs of active surveillance.

Active surveillance was born as a thera-peutic strategy for a well selected group of patients withlow risk prostate cancer with the aim to defer or com-pletely avoid the negative impact of secondary effectsof curative therapies. Nevertheless, the patient whochooses this treatment does it at the expense of greateranxiety and doubts about the possible progression of thedisease. The main psychological features influencing thequality of life of these patients are, on one hand anxiety,due to the uncertainty and fear to disease progression,and on the other hand, the difficult decision making pro-cess. Among the factors that seem to influence the elec-tion are: urologist`s recommendation, effects on urinaryfunction, age and impact of the therapy on sexual func-tion. In the timorous journey walked, it is recommendedto apply psycho-educational programs, with the objec-tive of increasing the perceived control and adaptiveconfrontation. We propose an intervention with 4 groupsessions, the objectives of which would be first to impro-ve the decision making process and diminish the fearto progression and, second to reinforce the informationalready given at the time of diagnosis and increase thesensation of control, e.g promoting healthy habits

Prostate cancer (PCa) represents a major public health burden in the western world. It is a peculiar disease as more men die with it than from it. Also interestingly, PCa was virtually unknown for centuries until the 20th century. Randomized trials on PCa screening have outlined the risks of over-diagnosis and over-treatment of latent cancers. Significant geographical differences in PCa incidence and mortality exist, being supposedly low among Asian men compared to Caucasians. In some areas like Korea and Japan, changes have been observed that cannot be explained easily by changing diagnostic procedures and increases in mortality may be due to lifestyles and dietary changes. We have recently studied and compared the prevalence of PCa in Caucasian (CAU) from Moscow, Russia and Asian (ASI) men from Tokyo, Japan. We chose a specific Cau population in Russia with little sun exposure and high fat diet but without widespread PSA screening. Autopsy data in western countries (North America and Europe) would have been heavily contaminated due to opportunistic PSA screening. Screening in Asi men in Japan is uncommon. Prostates were removed en-block with the seminal vesicles within 24 hours of death and analyzed in toto (perpendicular sections at 4 mm intervals) by an experienced uro-pathologist in Toronto. PCa was found on autopsy in a similar proportion of Russian Caucasian and Japanese men. Over 50% of cancers are Gleason ≥7 in Japanese and nearly 25% in Russian Caucasian men raising questions about 1) previous assumptions related to Asian PCa and 2) the notion of significant vs. insignificant cancers. Autopsy studies are key to improve our understanding of this very curious cancer.