The incorporation of prostatic specific antigen (PSA) to clinical practice revolutionized diagnosis and modified the epidemiology of prostate cancer (PCa). Although it lacks of many of the characteristics of an ideal tumor marker, it is the marker most used for diagnosis and follow up of any type of cancer. It represents the best clinical tool we currently have available for screening and staging of PCa. On the contrary, the greatest limitation PSA presents is its lack of tumor specificity. The use of PSA molecular derivatives and isoforms tries to solve, at least in part, its limitations. As a matter of fact, the use of % free PSA and PSAD significantly increases the test specificity for diagnosis and, the use of derivatives evaluating PSA temporary kinetics (PSAV and PSADT) represent very useful tools to estimate líquiprognosis during disease treatment and follow up. With the ongoing development of new markers for PCa, It is likely the role of PSA in diagnosis and staging of the disease will be modified.
The introduction and widespread adoption of PSA has revolutionized the way prostate cancer is diagnosed and treated. However, the use of PSA has also led to over-diagnosis and overtreatment of prostate cancer resulting in controversy about its use for screening. PSA also has limited predictive accuracy for predicting outcomes after treatment and for making clinical decisions about adjuvant and salvage therapies. Hence, there is an urgent need for novel biomarkers to supplement PSA for detection and management of prostate cancer. Despite the progress in developing new biomarkers, several obstacles remain before such biomarkers can be clinically used. These challenges include analytical and regulatory barriers, issues with study design and data analysis that lead to lack of reproducibility of promising results, and the lack of large scale trials to adequately assess the utility of promising biomarkers. In this article we discuss the challenges in biomarker research and the statistical considerations for biomarker evaluation. There is a plethora of promising blood and urine based biomarkers. For the purpose of this review, we focus on PSA derived forms, human kallikrein 2, Early Prostate Cancer Antigen, Transforming Growth Factor-Beta 1 and Interleukin-6, Endoglin, PCA3, AMACR and ETS Gene Fusions. These biomarkers have shown promise in early studies and are at various stages of development. However, in the future it is very likely that a panel of biomarkers will be used to achieve sufficient degree of certainty in order to guide clinical decisions. To be able to be used commercially such a panel will have to answer clinically relevant questions in a simple and cost-effective way.
With the pendulum swinging in low risk prostate cancer (PCa) to ideas of overtreatment and overdiagnosis more urologists are looking at Active Surveillance (AS) as a valid option for their low risk PCa patients. AS will undoubtedly hold a place as a management option in men with low risk PCa, however, it is critical to understand its limitations in its current form as highlighted in this article.We conducted a review of multiple computerized databases (Ovid, Medline, Pubmed, CINAHL, Cohrane Library database) with the keywords active surveillance, prostate neoplasm, and low risk PCa. Manual searches were also carried out. Assumptions of AS are discussed and their implications on selecting the appropriate AS candidate.As with any active treatment option offered to patients with PCa, those who are offered AS must be appropriately selected and counseled as to its risks and benefits.
Prostate cancer is the sixth most common cancer in the world (in the number of new cases), the third most common cancer in men, and the most common cancer in men in Europe, North America, and some parts of Africa. Different geographical regions have varying incidence and mortality. The risk of prostate cancer is increased by African-American ethnicity, increasing age, positive family history, and other factors such as diet. Nonetheless, the causes of prostate cancer are not well understood compared with other common cancers like lung and breast cancer. The introduction of prostate-speciﬁc antigen (PSA) screening made an enormous impact on the incidence of prostate cancer, which increased in the early 1990s and is currently down to pre-PSA screening levels. Screening has caused a change in pattern of disease to an earlier stage but not lower grade. Yet we know little about what causes this disease, in the past 10 years interest in and funding for prostate cancer research have increased and several promising risk modiﬁers have been identiﬁedeg, genetic predisposition, insulin growth factor (IGF) concentrations, and lycopene consumption.
Review analysis of prostate cancer among men of sub-Saharan West African descent in comparison to other ethnicities and men with a family history of prostate cancer.
There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemopreventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemopreven-tion agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.
In this bibliographic review we reexamine the different features in relation to indication, performance and interpretation of prostatic biopsy (PB).The main objective is to place methodological features involving PB in the current scientific scenario, establishing the correlation between the most relevant and analyzing the historic evolution this procedure has followed, particularly over the last two decades. Prostate biopsy has evolved to be a regular element in urologists` daily practice and its learning process has been simplified to the point it can be approached with adequacy during the first years of residency in Urology.This privileged position PB enjoys in daily practice and the performance obtained from it would have not been a reality without optimization of transrectal ultrasound or local anesthesia techniques, yet reviled in some forums, the real responsible of such success.configuTheconsensus reached in the various scientific associations, the clinical guidelines of which are widely consulted worldwide, is the best to support the current state of the art, being the starting point for the addition of new improvements to PB.
We analyze the main imaging techniques (transrectal ultrasound, Magnetic Resonance Imaging and Position Emission Tomography) that are currently used in the diagnosis and management of localised prostate cancer patients.We analyze the results that may be obtained with transrectal US and describe the latest advances in this technique (Doppler, power doppler and contrast media).With Magnetic Resonance Imaging, we describe the underlying principles, results and indications as well as some new applications (diffusion, perfusion, spectroscopy and the use of lymphotrophic nanoparticles).Finally we will describe the current state of positron emission tomography in diagnosis, follow up and recurrence detection using the different radiomarkers that are available.
OBJECTIVES: To review the various methods to predict the risk of having prostate cancer, or that localized disease may be cured or progress after a given treatment.METHODS: We performed a review of the various mathematic models known for the probability analysis of the event, with a critical analysis of weaknesses and strengths of each method. In a Medline update we review the most relevant papers referred to diagnosis and management of localized prostate cancer in its diagnosis and management sides, as well as the probability of developing metastatic disease and to die.RESULTS: There are multiple methods and models to predict the various events in a patient candidate to diagnosis of prostate cancer, as well as to analyze the possibilities of success of a specific treatment, in many cases with an important exactness. We emphasize the heterogeneity in the methods, data and variables used for the analysis, basically about retrospective studies. Many of the most sophisticated methods, Neural Network or cart, do not present greater exactness than classic methods like logistic regression.CONCLUSIONS: Predictive models are an important element for decision making in usual clinical practice, favoring the decision of a diagnosis or certain treatment is not taken in a random manner and therefore it is taken following scientific criteria. Waiting for more precise methods, we have to know no method is perfect, and therefore it is an important tool, which should not by pass personal knowledge or the experience of a specific working group.
Personalized medicine in the management of patients with prostate cancer consists of the integration of patient attributes such as age, genetic risk and comorbidities with specific clinical-pathologic variables including serum prostate specific antigen (PSA), imaging and features from the diagnostic prostate needle biopsy or prostatectomy specimen including tumor differentiation (i.e. Gleason), volume and extent of disease (i.e. tumor length and / or percentage, number of positive cores at diagnosis or pathologic stage post surgery including margin status). Although the development of various clinical statistical instruments such as nomograms have provided a mechanism to interrogate these variables, most urologists rely on basic prognostic features of stage, grade and PSA along with clinical judgment to define and understand individual risk and predict health outcomes. In addition, unlike other tumor types such as breast cancer, there are no routine ancillary diagnostic studies performed on the prostate needle biopsy or prostatectomy specimen to support and refine the treatment decision process for the individual patient. In this review we will provide a summary of the current practice of predictive modeling in prostate cancer and explore how technical advances in functional histology have played a role in the development and incorporation of a systems based platform for providing a patientspecific risk profile useful for clinical decision making.
OBJECTIVES: To compare methodologyand recommendations for the diagnosis of prostate can-cer between the different clinical Guidelines currentlyexistent.METHODS: We searched for clinical practice Guide-lines published in the period 2007-2009 in the webpages of the urological scientific associations, NationalGuideline clearinghouse, CMA infobase, and Trip data-base, as well as Pub Med. We found 4 clinical practiceguidelines matching the search criteria.RESULTS: All guidelines have been developed by a mul-tidisciplinary team, performing a previous systematic re-view. All of them except the AUA translate the scientificevidence in recommendations, although each of themuses a different classification. Only one of them hasbeen evaluated using the AGREE method.There are differences in the recommendation and useof diagnostic tests (PSA, digital rectal examination andprostatic biopsy) due to the fact that as a general rulethey are based on low level scientific evidence.CONCLUSIONS: Recommendations for the diagnosisof prostate cancer in all clinical practice guidelines arebased on low levels of evidence, except in the use of an-tibiotic prophylaxis and anesthesia to perform a biopsy
Active surveillance is a solution to the widely acknowledged problem of overdiagnosis and overtreatment of clinically insignificant disease which accompanies early detection of prostate cancer using PSA and biopsy. It is an approach to the management of favorable risk prostate cancer which uses the opportunity provided by the long natural history of the disease to incorporate a period of initial observation into patient management. In this review article, the rationale, criteria for patient selection, method of follow up, trigger for intervention, and results of active surveillance are reviewed.
The stage migration for newly diagnosed prostate cancer, improvements in prostate imaging, and devices capable of inducing subtotal prostate ablation have allowed for the formal study and evaluation of focal therapy for low-risk prostate cancer. Significant limitations remain: 1) the need for more accurate pre-treatment determination of cancer location, extent, and size, 2) determining appropriate methods of post-treatment surveillance and definitions of clinical progression, 3) the uncertainty whether repeat treatment, by focal or whole-gland therapy, is effective and safe. Clinical trials are ongoing to provide data on the feasibility and reliability of these new therapies, the capability of eradicating cancers, rates of secondary treatment, and impact on urinary and sexual function.
OBJECTIVES: The robotic-assisted laparoscopic approach to radical prostatectomy is increasingly utilized and has become well documented as an effective oncologic treatment modality. In this study, we report the initial experience of a single surgeon at a single institution with robotic-assisted laparoscopic prostatectomy (RALP) drawing a comparison to his prior experience with pure laparoscopic prostatectomy (LRP). METHODS: This is a retrospective review of surgical results from a single surgeon performing LRP and transitioning to RALP. Baseline characteristics and outcomes of two hundred seventy five patients undergoing RALP by a single, fellowship-trained, urologic oncologist were analyzed and compared to 45 patients undergoing LRP by the same surgeon. Patient, tumor, and operative characteristics as well as functional outcomes were evaluated. Validated questionnaires, including the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF), were utilized in the assessment of urinary and sexual parameters. RESULTS: Preoperative patient and tumor characteristics (age, PSA, Gleason score) were similar in both the LRP and RALP groups. Mean operative time (195 vs. 299 minutes), estimated blood loss (223 vs. 299 mL), need for blood transfusion (1.5% vs. 4.4%) and mean length of stay (1.95 vs. 2.63 days) were significantly reduced among patients undergoing RALP as compared to those undergoing LRP. In terms of functional outcomes, continence at 12 months was better among patients undergoing RALP as compared to LRP (94% vs. 82%). In preoperatively potent men undergoing bilateral nerve sparing procedures, RALP conferred 82% potency at 24 months as opposed to only 62% following LRP.CONCLUSIONS: The combination of adjustment in surgical technique from LRP to RALP along with a concurrent institutional commitment to a successful robotic surgery program, has yielded superior operative, oncologic, and functional results.
OBJECTIVE: The robotic technique has been associated with a decreased LC for radical prostatectomy. The objective is to review the literature in search of any evidence that the RALP is able to shorten the learning curve for radical prostatectomy compared to the open and pure laparoscopic techniques. METHODS: A Medline search of the English-language literature was performed to identify all papers published relating to RALP and LC. RESULTS: There is substantial variability in the RALP literature regarding the number of cases a surgeon needs to achieve and sustain in time acceptable operative times and reasonable outcomes. The information on RALP LC comes from isolated single institution reports with questionable methodological analyses. There are no studies comparing the LC of RALP with open or pure laparoscopic techniques.CONCLUSIONS: There is no reliable information to support the notion that RALP shortens the prostatectomy LC. The evidence is limited to case series, with a Level of Evidence 4.
The last 10 years have witnessed unprecedented evolution regarding de surgical removal of the prostate gland. Laparoscopic radical prostatectomy broke the open paradigm and started to generate great excitement and expectations. Shortly however, robot-assisted, laparoscopic – Robotic Surgery – emerged to address a fundamental pitfall of prostate laparoscopic surgery: execution reproducibility. Today, robotic assisted laparoscopic prostatectomy is the most used surgical approach to remove the prostate gland. Consistent advantages of this technique are: a shorter convalescent state, marked decrease in blood loss and in experienced hands, shorter average surgical times. Importantly, it served to highlight the importance of outcomes as ultimate judge of a procedure success. The data suggest equivalency in long-term functional and oncological outcomes, while clear advantages in the short run: perioperative outcomes with patient rapid return to productive state. That said, the major challenge for robotic surgeons still remains: establish a paradigm that breaks with the tradition and prevents biased reporting due to technology and marketing enthusiasm, but rather takes a critical approach based in prospective, controlled, randomize clinical trials. If the latter objective is reached, urologic robotic surgeons will deliver counseling based on clinical evidence delivering major progress for our Urology field.
The objective of this review is to present an overview of each modality and delineate how to best select patients who are optimal candidates for these treatment approaches. Prostate brachytherapy as a curative modality for clinically localized prostate cancer has become increasingly utilized over the past decade; 25% of all early cancers are now treated this way in the United States (1). The popularity of this treatment strategy lies in the highly conformal nature of radiation dose, low morbidity, patient convenience, and high efficacy rates. Prostate brachytherapy can be delivered by either a permanent interstitial radioactive seed implantation (low dose rate [LDR]) or a temporary interstitial insertion of iridium-192 (Ir192) afterloading catheters. The objective of both of these techniques is to deliver a high dose of radiation to the prostate gland while exposing normal surrounding tissues to minimal radiation dose. Brachytherapy techniques are ideal to achieve this goal given the close proximity of the radiation source to tumor and sharp fall off of the radiation dose cloud proximate to the source. Brachytherapy provides a powerful means of delivering dose escalation above and beyond that achievable with intensity-modulated external beam radiotherapy alone. Carefull selection of appropriate patients for these therapies, however, is critical for optimizing both disease-related outcomes and treatmentrelated toxicity.
Androgen deprivation plays a major role in the treatment of prostate cancer. Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone. This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer.