Prostate-specific membrane antigen (PSMA) is the most extensively studied biomarker and antigen of prostatecancer. It is overexpressed in almost all prostate cancers, and the expression level increases with prostatecancer progression. PSMA is also highly expressed in the neovasculature of solid tumours including prostatecancer. As a result, numerous PSMA-specific ligands have been discovered for prostatecancerdiagnosis and therapy, and one of them has been approved for clinical use. Moreover, a number of other PSMA-specific ligands are currently evaluated in clinical studies. In this review we discuss four major types of PSMA-specific ligands, including antibody, aptamer, peptide, and small molecule inhibitor. Their emerging applications in prostatecancerdiagnosis, targeted drug delivery, and therapy are also discussed.
As an advanced imaging technique, MRI has been gaining acceptance as an important tool in the evaluation of prostate diseases. T2WI is an important traditional sequence for the diagnosis of prostatecancer in the prostate peripheral zone but not specific. It is easy to distinguish the cancerous area which presents hypointense on T2WI from the uniform hyperintense background in the prostate peripheral zone. However, other changes such as prostatitis and fibrosis also can appear hypointense on T2WI . Furthermore, although most of cancers arise in the peripheral zone of the prostate, up to 30% of prostate cancers occur within the central region . It is more difficult to discriminate malignant from benign prostatic hyperplasia because transition zone cancer is the site of origin of benign prostatic hyperplasia, which can have a heterogeneous appearance . Although diffusion weighted imaging (DWI), magnetic resonance spectros- copy (MRS) and dynamic contrast enhanced (DCE) imaging may provide supplementary information for the diagnosis of prostate disease, as each method has its own deficiencies, overlap appears in the differential diagnosis between prostatic cancer and benign prostatic hyperplasia .
The conventional PSA cutoff of 4.0ng/dL detects most cases of prostatecancer; however, some cases will be missed. Using a lower cuto- ff point detects more cases of cancer but at the cost of labeling more men as potentially having the disease. When the PSA cutoff decreases to 2.5ng/dL more than double the number of men aged 40 to 69, with abnormal results, show a fal- se positive result. This cutoff level also increases the likelihood of detection of indolent tumors with no clinical importance. Conversely, increa- sing the PSA cutoff to a level greater than 10ng/ dL would reduce a prostatecancerdiagnosis in the number of men aged 50 to 69 with abnormal results from 1.2 million to roughly 352,000. It is important to note there is no PSA cutoff at which a man can be guaranteed to be free from prostatecancer (21, 22).
All data for this study are from the PCPT (SWOG-9217) [15,16]. Details of the study design and participant characteristics have been described previously [15,16]. Briefly, 18,882 men age 55 years and older with a normal digital rectal exam (DRE), prostate specific antigen (PSA) level of 3 ng/mL or below, and no history of prostatecancer or other clinically significant co- morbid conditions that would have precluded successful completion of the study protocol, were randomized to receive either finasteride (5 mg/day) or placebo daily for seven years. Dur- ing the course of the PCPT, men underwent annual DRE and PSA measures and a prostate bi- opsy was recommended for all men with an abnormal DRE or a finasteride-adjusted PSA of > 4.0 ng/mL. At the conclusion of the trial, either a prostatecancerdiagnosis or end-of- study biopsy was available from 59.6% of the participants in the finasteride treatment arm, and 63% from the placebo arm. This level of ascertainment agreed well with the study design as- sumption that 60% of men would have an endpoint assessed. All men signed informed consent and study procedures were approved by the Institutional Review Boards of the participating 221 study sites [15,16].
We used the multiplex semi-quantitative reverse-transcriptase PCR (RT-PCR) to investigate kallikrein 2 and 3 (KLK2 and KLK3) mRNA levels in prostate tissue from 42 prostatecancer patients, 33 of whom were also assessed for pe- ripheral blood KLK2 expression by qualitative semi-nested RT-PCR. We found that KLK2 was an important tissue biomarker for distinguishing between prostatecancer patients and those with benign prostatic hyperplasia, particu- larly when KLK2 expression was > 60% of that of the β2-microglobulin constitutive gene. Patients with an average relative expression value ≥ 0.6 (cutoff value) had an eleven-fold higher chance of having prostatecancer. When one or two tissues samples were evaluated for KLK2 expression using the cutoff value the estimated chance of having prostatecancer was increased by seven times for one positive sample and 45 times for two positive samples. There was no significant correlation between KLK3 gene expression and prostatecancerdiagnosis. Logistic regression for blood and tissue KLK2 expression successfully detected 92% of the prostatecancer cases. The detection of KLK2 in blood showed a sensitivity of 59% and a specificity of 82%. This study indicates that the KLK2 gene may be a useful molecular marker for the diagnosis of prostatecancer and that analysis of KLK2 expression in blood and tissues could provide a novel approach for the clinical investigation of this type of cancer.
role contributing to the dissemination of this method. The text describes and illustrates the techniques utilized in mpMRI of the prostate, emphasizing the essential requirements that should be met by each functional technique, diffusion-weighted imaging, dynamic contrast-enhancement, and proton spectroscopy proto- cols, as well as by high-resolution T2-weighted imaging protocols. The authors highlight the main imaging findings of prostatecancer considered in both the diagnosis and staging of the disease. Fi- nally, the authors approach the main mpMRI applications, includ- ing those that are already accepted and those that, although de- scribed in several studies, still lack a greater amount of data to achieve the level of evidence required for dissemination of the method in the clinical practice.
tant to note that, despite the continuous progress of imaging methods, particularly magnetic resonance imaging, searching for a correct diagnosis of prostatecancer, transrectal ultrasound (US) guided biopsy still plays a fundamental role for histopathological confirmation. Although such procedure is considered secure and also well tolerated by most patients, studies demonstrating com- plications in up to 73% of patients cannot be ignored (3) , leading
Many predictive models to diagnosis PC at initial biopsy have been made mostly with Western data [6,8,11,12]. Even though these predictive tools have been validated in the Western population, their extrapolation to Asian, or more specifically to Korean patients should be done with caution [13,14]. The predictive accuracies of ERSPC-RC and PCPT-RC in their original cohorts were 0.79 and 0.70, respectively. When applying these 2 risk calculators to the validation cohort consisting of Korean men, the accuracies were 0.768 and 0.704, respectively. In contrast, SNUPC-RC statistically outperformed ERSPC-RC and PCPT-RC with an accuracy of 0.811. The DCA also indicated a higher clinical benefit with SNUPC-RC than with ERSPC-RC and PCPT-RC. In the sub-population analysis among an age group of 55–69 years, AUC of SNUPC-RC was also statistically higher than those of ERSPC-RC and PCPT-RC. We selected this age group as this has shown the most benefit for PSA screening in the ERSPC trial . The outperformance of SNUPC-RC may be caused by the different characteristics of the population and different practice patterns. The PSA screening rate in Korea is still lower than that in Western countries . Furthermore, healthy Korean men have lower normal levels of PSA than their age-
Prostatecancer (PCa) remains as one of the most common cause of cancer related death among men in the US. The widely used prostate specific antigen (PSA) screening is limited by low specificity. The diagnostic value of other biomarkers such as RAS association domain family protein 1 A (RASSF1A) promoter methylation in prostatecancer and the relationship between RASSF1A methylation and pathological features or tumor stage remains to be established. Therefore, a meta-analysis of published studies was performed to understand the association between RASSF1A methylation and prostatecancer. In total, 16 studies involving 1431 cases and 565 controls were pooled with a random effect model in this investigation. The odds ratio (OR) of RASSF1A methylation in PCa case, compared to controls, was 14.73 with 95% CI = 7.58–28.61. Stratified analyses consistently showed a similar risk across different sample types and, methylation detection methods. In addition, RASSF1A methylation was associated with high Gleason score OR=2.35, 95% CI: 1.56–3.53. Furthermore, the pooled specificity for all included studies was 0.87 (95% CI: 0.72–0.94), and the pooled sensitivity was 0.76 (95% CI: 0.55–0.89). The specificity in each subgroup stratified by sample type remained above 0.84 and the sensitivity also remained above 0.60. These results suggested that RASSF1A promoter methylation would be a potential biomarker in PCa diagnosis and therapy.
OBJECTIVE: To report an experiment involving the introduction of a protocol utilizing commercially available three-dimensional 1H magnetic resonance spectroscopy imaging (3D 1H MRSI) method in patients diagnosed with prostatic tumors under suspicion of neoplasm. MATERIALS AND METHODS: Forty-one patients in the age range between 51 and 80 years (mean, 67 years) were prospectively evaluated. The patients were divided into two groups: patients with one or more biopsies negative for cancer and high specific-prostatic antigen levels (group A), and patients with cancer confirmed by biopsy (group B). The determination of the target- area (group A) or the known cancer extent (group B) was based on magnetic resonance imaging and MRSI studies. RESULTS: The specificity of MRSI in the diagnosis of prostatecancer was lower than the specificity reported in the literature (about 47%). On the other hand, for tumor staging, it corresponded to the specificity reported in the literature. CONCLUSION: The introduction and standardization of 3D 1H MRSI has allowed the obtention of a presumable diagnosis of prostatecancer, by a combined analysis of magnetic resonance imaging and metabolic data from 3D 1H MRSI.
The ERSPC 10 study, which clearly showed a reduction in PCa-specific mortality due to screening, was based on a 2–4 year PSA screening interval. However, further subanaly- ses of the study seemed to support a potential for even fur- ther risk stratification and prolongation of screening time in- terval. For example, Roobol et al. 22 evaluated a group of men with initially low PSA (< 1ng/mL) who underwent every 4–8 years screening interval and found only 0.23% risk of cancerdiagnosis during the intervening visit. Another study showed a 0.5% risk of advanced disease and overall 2.5% risk of prostatecancer at 15 years follow-up 23 . On the other hand, van Leeuwen et al. 24 compared men from Goth- enburg screening cohort (2-year screening interval) to Rot- terdam cohort (4-year screening interval) and found that more frequent screening resulted in a higher proportion of screen-detected cancers (RR:1.18, p = 0.009). However, more frequent screening also led to increased incidence of clinically insignificant (low-risk) PCa (RR: 1.46, p < 0.001). Interestingly, the Gothenburg cohort also had a lower inci- dence of advanced cancer during the last follow-up (RR: 0.57, p = 0.048), which implied that more frequent screening resulted into more effective way of eliminating high-risk PCa from the population. Importantly, the effect on PCa-related mortality remained uncertain. This study implies that there is a certain population of men that may benefit from a more frequent screening program, but an individualized approach according to patient risks would be the most optimal way of screening. Currently, there is no data that supports annual PSA screening for PCa – the best evidence is based on screening every 4 years 10 .
Identification of cancer was based on individuals’ responses to the questions asking ‘‘List any significant past medical illness or health problems’’ and ‘‘List any previous injuries and/or surgeries’’. It was assumed a diagnosis of cancer was a significant enough event in the life of participants for almost full reporting. Keywords used to identify malignancies were ‘‘cancer’’, ‘‘cancer- ous tumour’’, ‘‘malignant tumour’’, ‘‘malignancy’’ or specific individual malignancies such as ‘‘melanoma’’. In addition, reporting a surgery or procedure that would be undertaken exclusively for a particular cancer was included as a cancer item (e.g., patients having undergone a radical prostatectomy were assumed to have had prostatecancer). No benign tumours were classified as cancers. For all cancers identified, the following details were noted: (1) year of diagnosis; (2) tumour type (e.g., carcinoma or sarcoma); and (3) the organ affected.
Determination of serum levels of prostate- -specific antigen (PSA) has been used in clinical practice since 1988, and has become the most va- luable tumor marker widely used in screening for prostatecancer. It is considered to be responsible for 45-70% of decreased PC-related deaths repor- ted since 1990 (3). The production of PSA occurs mainly in epithelial cells located in the transition zone (TZ), which makes it organ-specific, but not cancer-specific. Therefore, a multi-parameter ap- proach is essential, given that PSA value taken singularly is not sufficiently accurate, due to the interference of age and frequently coexisting con- ditions, such as benign prostate hyperplasia (BPH) and prostatitis (4). It seems to be difficult to discri- minate between prostatecancer and benign condi- tions especially among patients with intermediate PSA levels between 2.6 and 10 ng/mL (5). Within this range, there is a trade-off between specificity and sensitivity, a significant degree of the former being lost in the interest of achieving an accepta- ble degree of the latter (6). In other words, many patients are submitted to unnecessary biopsies because it is important to maintain acceptable diagnosis rates. Therefore, approximately 70% of prostate biopsy results are negative in this group (7). Different PSA parameters such as PSA velocity (6), age specific reference ranges (7), PSA densi- ty (PSAD) (8), PSA density adjusted by transition zone (PSATZ) (9) and the correlations between its molecular forms, have been introduced to improve the diagnostic accuracy of serum PSA. However, it remains unclear which method is superior in routine use. Recent studies like PROMIS (10) sho- wed that multiparametric MRI as a first strategy to diagnose PC is effective and cost effective; ho- wever, in developing countries such as Brazil, this is not a reality in the great majority of our public health system. Therefore, simpler and most avai- lable approaches to evaluate PSA parameters and PC screening are warranted.
Abstract: Goal: describe the epidemiological profile of the men’s population assisted by the tent of urology in the 8th Campaign of prevention and early diagnosis of cancer in the municipal of Montes Claros, Minas Gerais and show the changes identified. Methodology: A descriptive and quantitative study carried out with data obtained from the care records from the population assisted in the Campaign of 2018. The data were presented in graphs. For tabulation and analysis, SPSS statistical software was used. Results: In the urology tent 572 individuals with the average of 60,7 years were assisted, in which more than half (66,8%) were married or with a stable relationship and had education until elementary school (68,1%). The evaluations identified 151 men with enlarged prostate. In 26 men (4,6%) there was node. 48 digital exams were altered, where 39 were biopsied and 16 cases confirmed prostatecancer. Conclusion: The Prevention and Early Diagnosis of Cancer Campaign, promoted tracking and the early diagnosis of prostatecancer, through the collection of PSAs, following the evaluation of the urologists, that when identifying significant changes in some of the men assisted population, progressed to biopsy and confirmed cases for specific cancer treatment.
Circulating tumor cells (CTCs) have been implicated as potential seeds of cancer metastasis and are therefore of great importance in research, disease management, and drug develop- ment [1–3]. Established methods for capturing these cells, such as the Veridex CellSearch H system (Raritan, NJ, USA), rely on affinity capture of the epithelial cell surface antigen, EpCAM, followed by fluorescence labeling of intracellular cytokeratin (CK) [4–6]. While CTC identification and enumeration, based on epithelial biomarker expression, can be used to predict poor clinical outcome [7–10] this strategy may be prone to underes- timation of CTC number because of epithelial-to-mesenchymal transition [11–14], poor expression of these factors in some tumor types , or changes in expression of these factors following chemotherapy . These limitations may be particularly relevant, given that the appearance of mesenchymal CTCs is associated with disease progression  and the inclusion of additional criteria CTC identification may be a valuable supplement to conventional CellSearchH CTC enumeration.
Efficacy and safety of radium-223 dichloride in patients with castration- resistant prostatecancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPC trial. Lancet Oncol. 2014; 15(12):1397-406. 7. Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostatecancer and bone metastases: Results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014; 15(7):738-46. 8. Nilsson S, Strang P, Aksnes AK, Franzèn L, Olivier P, Pecking A, et al. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostatecancer. Eur J Cancer. 2012; 48(5):678-86. 9. Parker CC, Pascoe S, Chodacki A, O'Sullivan JM, Germá JR, O'Bryan-
Finalizing this discussion, it is important to note that the authors in this category reported that the tracking exams for prostatecancer are, surely, the most important step of this treatment, because it is at this early stage of the disease that it has the opportunity to offer men a, effective and cheaper treatment method, as well as contributes to the maintenance of the quality of lifestyle, as the scans are practical checkups associated with campaigns for the reduction of diseases. However, the implantation of tracking policies, experts say, requires preventive practices are effective in reducing mortality rates of a given disease. And, according to the INCA, this does not happen with prostatecancer. On the other hand, according to the INCA, at the moment there is no evidence that the tracking for prostatecancer to identify individuals who need treatment or that this practice reduce mortality from prostatecancer. In this way, the INCA does not recommend tracking for prostatecancer, since the decision of the use of the trace as a public health strategy must be based on quality scientific evidence. 1,23
The timing of cystectomy in T1 bladder cancer is a matter of debate since years. Here, the authors from a tertiary referral center present their series of 523 patients and analyze variables which may help with the deci- sion to remain conservatively, or proceed with radical surgical therapy. Interestingly, re-TUR was performed in all patients and yielded a high rate of 20% upstaging to muscle-invasive disease. If true T1 was considered, the disease-speciic mortality at 5 years was 10%, with no survival differences between those patients undergoing early cystectomy versus those with no or deferred cystectomy. Clearly, these data support an initial conservative approach in select patient with true pT1. In any case, a re-TUR is mandatory.