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Reasons why significant prostate cancer is still missed in early stage were investigated at the 22nd National SIEUN (Italian Society of integrated diagnostic in Urology, Andrology, Nephrology) congress took place from 30th November to 1st December 2020, in virtual modality. Even if multiparametric magnetic resonance (MR) has been introduced in the clinical practice several, limitations are emerging in patient with regular digital rectal examination (DRE) and serum prostate specific antigen (PSA) levels approaching the normal limits. The present paper summarizes highlights observed in those cases where significant prostate cancer may be missed by PSA or imaging and DRE. The issue of multidisciplinary interest had been subdivided and deepened under four main topics: biochemical, clinical, pathological and radiological point of view with a focus on PI-RADS 3 lesions. [ABSTRACT FROM AUTHOR]

The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation (ASAP) are more likely to progress to prostate cancer (PCa). Androgens have long been considered to be the potential risk factors for PCa. However, the role of testosterone is controversial. The present study aims to analyze the relationship between serum testosterone (TS) levels and the diagnosis of PCa after a first prostate biopsy in patients affected by ASAP. This retrospective study included 143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa according to the European Association of Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal examination, and prostate biopsy Gleason score (GS) were collected retrospectively for statistical analysis. All patients included in the study had a second biopsy and were suitable for further analysis. Re-biopsy was carried out 3-6 months after the first diagnosis of ASAP. Low and normal TS groups were composed of 29 (20.3%) and 114 (79.7%) patients, respectively. The diagnosis of the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison between patients with PCa and those with negative or an ASAP result in the second biopsy reported that men with cancer had significantly higher levels of TS (P < 0.001). However, there was no statistically significant association between GS postbiopsy and TS (P = 0.324). Our experience demonstrated that eugonadal patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy after ASAP diagnosis than hypogonadal. [ABSTRACT FROM AUTHOR]

• Prostate cancer with seminal vesicle invasion (SVI) has been considered as aggressive cancer. However, SVI does not always correlate with a poor prognosis. • We evaluated the prognostic significance of the different Ohori's patterns of isolated SVI and negative lymph nodes in patients undergoing robotic radical prostatectomy. • We found that positive surgical margin status was the only predictor of biochemical recurrence (BCR) in patients with isolated SVI. • The presence of cancer island(s) in the seminal vesicle was associated with a significantly shorter time to BCR compared to other patterns, and time to BCR was even shorter in men with negative surgical margins. Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172–29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns. [ABSTRACT FROM AUTHOR]

Introduction: Treatment planning in patients with prostate neoplasms and prostate cancer (PCa) is generally based on the clinical and pathological molecular markers obtained from prostate needle biopsy and/or radical prostatectomy specimens. Area covered: Pathology of prostate neoplasms is evolving rapidly. Emerging trends include new additions to the 2016 World Health Organization (WHO) tumor classification as well as expanded diagnostic utility of biomarkers and molecular testing in tissue specimens, liquid biopsies and urinary samples, with the following purposes: diagnosis, prognosis and prediction. Expert commentary: The new additions to the 2016 WHO tumor classification, which include pathological definition of Intraductal carcinoma of the prostate (IDC-P) and of a new grading system for PCa, as well as identification of molecular markers, such asTMPRSS2-ERGandAR-V7, may pave the way to personalized therapy for patients with prostate tumors. [ABSTRACT FROM PUBLISHER]

Introduction: The incidence of benign testicular tumors is increasing in particular in small lesion incidentally found at scrotal ultrasonography. Primary aim of this study was to perform radical surgery in malignant tumor. Secondary aim was to verify the efficacy of the diagnostic-therapeutic pathway recently adopted in management of small masses with testis sparing surgery in benign lesions. Materials and methods: In this multicenter study, we reviewed all patients with single testis lesion less than 15 mm at ultrasound as main diameter. We applied the diagnostic-therapeutic pathway described by Sbrollini et al. (Arch Ital Urol Androl 2014; 86:397) which comprises: 1) testicular tumor markers, 2) repeated scrotal ultrasound at the tertiary center, 3) surgical exploration with inguinal approach, intraoperative ultrasound, and intraoperative pathological examination. Definitive histology was reviewed by a dedicated uro-pathologist. Results: Twenty-eight patients completed this clinical flowchart. The mean lesion size was 9.3 mm (range 2.5-15). Testicular tumor markers were normal except in a case. Intraoperative ultrasound was necessary in 8/28 cases. We treated 11/28 (39.3%) with immediate radical orchiectomy and 17/28 (60.7%) with testis-sparing surgery. Definitive pathological results were: malignant tumor in 6 cases (seminoma), benign tumor in 10 cases (5 Leydig tumors, 2 Sertoli tumors, 1 epidermoid cyst, 1 adenomatoid tumor, 1 angiofibroma), benign disease in 11 (8 inflammation with haemorragic infiltration, 2 tubular atrophy, 1 fibrosis), and normal parenchyma in 1 case. We observed a good concordance between frozen section examination and definitive histology. Any malignant tumor was treated conservatively. Any delayed orchiectomy was necessary based on definitive histology. Conclusions: The incidence of benign lesions in 60% of small testis lesions with normal tumor markers makes orchiectomy an overtreatment. Testicular sparing surgery of single testicular nodules below 15 mm is a safe option, but requires a standardized pathway in diagnosis. Our pathway has shown good reliability and security profile to be applied in a multicenter management for small scrotal masses. Our study has shown the reliability of the diagnostic-therapeutic pathway in the management of single testicular masses. The higher incidence of benign lesions in 60% of patients makes often orchiectomy an overtreatment. [ABSTRACT FROM AUTHOR]

Purpose: Prostatic calculi (PC) are usually associated with benign prostatic hyperplasia or chronic inflammation. However, in several studies prostatic inflammation and calcification have been implicated in the pathogenesis of prostate cancer (CaP). We evaluated the prevalence of PC during transrectal ultrasound (TRUS) and correlate the ultrasonographic patterns with histological findings. Methods: A prospective study of 664 patients undergoing TRUS and prostate biopsy was planned. A standardized reproducible technique was used with using a GE Logiq 7 machine equipped with a 5-9MHz multi-frequency convex probe "end-fire". We defined marked presence of PC as multiple hyperechoic foci with significant area (≥ 3 mm in the largest diameter). PC were classified according to zone distribution into the gland: transitional zone (TZ), central zone (CZ), and peripheral zone (PZ). Results: No significant difference was noted between the patients with PC and without PC, when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for DRE findings. 168 patients (25.3%) had marked presence of PC on TRUS: 50.6% in TZ, 20.2% in CZ, and 29.2% in PZ. 31 patients (63.3%) with presence of PC in PZ had CaP on biopsy. The correlation observed between CaP and the presence of PC in PZ was statistically significant (p < 0.001). However, among patients in the CaP group there was no statistical association between PC and moderate or high Gleason grade. Conclusions: This study suggests that chronic prostatic inflammation and PC have a role in the biogenesis of cancer. CaP was more frequent in patients with PC in PZ of the gland, but was not associated with higher Gleason grade among these patients (p < 0.001). [ABSTRACT FROM AUTHOR]

We describe our experience in prostate biopsy using a new standardized cognitive fusion techniques, that we call "cognitive zonal fusion biopsy". This new technique is based on two operative options: the first based on target biopsies, the Cognitive Target Biopsy (CTB) if the same target was detected with transrectal ultrasound (TRUS) and multiparametric magnetic resonance (mpMRI); the second based on saturation biopsies, the Zonal Saturation Biopsy (ZSB) on anatomical zone/s containing the region of interest if the same target was not evident with TRUS and MRI. We evaluated results of our technique compared to standard biopsy in order to identify clinically relevant prostate cancer. Methods: This is a single-center prospective study conducted in 58 pts: 25 biopsy-naïve, 25 with previous negative biopsy and in 8 with cancer in active surveillance. Based on mpMRI and transrectal ultrasonography (TRUS), all patients were scheduled for standard 12-core TRUS-guided biopsy. If mpMRI was suggestive or positive (PI-RADS 3, 4 or 5): patients underwent additional targeted 2 to 6 cores using cognitive zonal fusion technique. Results: 31/58 (53.4%) patients had a cancer. Our technique detected 80.6% (25 of 31) with clinically significant prostate cancer, leading to detection of insignificant cancer in 20%. Using standard mapping in MR negative areas we found 5 clinically significant cancer and 4 not significant cancers. MRI cancer detection rate was 18/31 (58.1%), and 9/18 (50%) in high grade tumors. Therefore MRI missed 50% of high grade cancers. The mean number of cores taken with cognitive zonal fusion biopsy was 6.1 (2-17), in addition biopsy sampling was done outside the ROI areas. Overall 15.4 cores (12-22) were taken. Cancer amount in Zonal Biopsy was larger than 7.3 mm (1-54.5) in comparison with 5.2 mm (1-23.5) in standard mapping. Largest percentage of cancer involvement with cognitive zonal fusion technique was detected in 19.4% vs 15.9%. Conclusions: Cognitive Zonal Saturation Biopsies should be used to reduce operator variability of cognitive fusion biopsy in addition to standard biopsy. Cognitive zonal biopsy based on mpMRI findings identifies clinically relevant prostate in 80%, has larger cancer extension in fusion biopsies than in random biopsies, and reduce the number of cores if compared to saturation biopsy. [ABSTRACT FROM AUTHOR]

The Gleason grading system was developed in the late 1960s by Dr. Donald F. Gleason. Due to changes in prostatic adenocarcinoma (PAC) detection and treatment, newer technologies to better characterize prostatic pathology, subsequently described variants of PAC and further data relating various morphologic patterns to prognosis, the application of the Gleason grading system changed substantially in surgical pathology. First in 2005 and more recently in 2014, consensus conferences were held to update PAC grading. Here, we review of the successive changes in the grading of PAC from the original system, with emphasis on the newest prognostic grade grouping. [ABSTRACT FROM PUBLISHER]

Hormone and radiation therapy have traditionally been used in prostate cancer (PCa). Morphological effects are often identified in needle biopsies and surgical specimens. A range of histological changes are seen in the non-neoplastic prostate and in the pre-neoplastic and neoplastic areas. Other ablative therapies, including cryotherapy, and emerging focal therapies, such as high-intensity focused ultrasound, photodynamic therapy and interstitial laser thermotherapy, may induce changes on the prostate. As new compounds are developed for prostate cancer treatment, it is important to document their effects on benign and neoplastic prostate tissue. [ABSTRACT FROM AUTHOR]

Background The aim of this report is related to adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of the spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of these lesions arise from the spermatic cord, 20% being leiomyosarcoma. Tumor grade, stage, histologic type, and lymph node involvement are independently predictive of prognosis. Case description The case report concerns a 81-year-old man presented with a 3-year history of painless lump in the right hemiscrotum. Scrotal examination demonstrated a 5.1-cm, firm-to-hard mass attached to the spermatic cord. Scrotal ultrasound scan revealed a heterogeneous mass separate from the testis. He was treated with an radical orchi-funicolectomy. Histologically the lesion is composed of spindled cells with often elongated, blunt-ended nuclei and variably eosinophilic cytoplasm. Areas with pleomorphic morphology are present. The level of mitotic activity is equal to 3/10 HPF in the areas with spindle cell morphology and to 12/10 HPF in the areas with pleomorphic morphology. The final diagnosis was that a leiomyosarcoma of the spermatic cord, with grade 1 and grade 2 areas, stage pT2b cN0 and cM0. The patient has been followed up for 3 months with CT scans and shows no signs of recurrence. Conclusion Spermatic cord leiomyosarcoma, although rare, should be one of the first differential diagnoses for a firm-to-hard lump in the cord. Apart from radical orchi-funicolectomy, there has been added benefit of adjuvant radiotherapy to prevent any loco-regional lymph node recurrence. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1613030331125632 [ABSTRACT FROM AUTHOR]

Pseudoaneurysm (PA) associated with an arteriovenous fistula (AVF) of the internal pudendal artery branches are very uncommon. We report a case of post-traumatic PA with AVF connected to Santorini plexus. Diagnosis was made with trans-rectal ultrasound (TRUS) after recurrent hematuria. TRUS reported a 1.7 × 1.4 × 1.5 cm anechoic area, on anterior prostate apex close to Santorini plexus. The use of color Doppler in this area revealed high flow velocity that was indicative for AVF. The feeding artery was a distal branch of the left pudenda artery. After selective embolization was observed complete occlusion of the feeding branches and disappearance of PA with AVF. Prostate PA with concomitant symptomatic AVF detected with TRUS has not yet described in literature after pelvic trauma and represents complex diagnostic challenges. This case report suggests that the use of TURS and color Doppler can provide an important diagnostic and follow-up to address the clinical suspicion of occult vascular injuries using a noninvasive approach. [ABSTRACT FROM AUTHOR]

Introduction: Testicular benign tumors are very rare (< 5%). Testicular Angiofibroma (AF) is one of those, however the gold standard of treatment and follow-up is still unclear. Case report: A 47 years-old man with only one functioning testis was referred to our clinic for a palpable right testicular mass and atrophic contralateral testis. Patient underwent testis-sparing surgery with inguinal approach and intraoperative frozen sections examination with diagnosis of AF. Final histology confirmed AF. Post-operative follow-up was uneventful. Clinical and ultrasonographic follow-up was negative after 8 months. Conclusion: We report a conservative surgery in a patient with AF of the solitary testis. AF is a benign para-testicular fibrous neoplasm that could be misinterpreted as malignant tumor and treated with orchiectomy. Testis-sparing surgery is recommended in this case with intraoperative pathological examination. The excision of the mass is enough but in front of a possible recurrence a long follow-up is advisable. [ABSTRACT FROM AUTHOR]

Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and wholeexome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors. [ABSTRACT FROM AUTHOR]

Abstract: The clinical and radical prostatectomy features of a case of solitary fibrous tumour (SFT) of the prostate identified on needle biopsy are presented. The main differential diagnoses are discussed. SFTs involving the prostate are relatively uncommon, with only isolated cases reported in the literature. Owing to their relative rarity and lack of long-term follow-up, the clinical behaviour of prostatic SFTs is difficult to predict. Complete resection of the tumour is currently the single main prognostic factor. [Copyright &y& Elsevier]

Background and aim of the study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. Materials: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. Results: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively). [ABSTRACT FROM AUTHOR]

Objective: High serum total prostate-specific antigen (PSA) levels have proven to be predictive of concurrent cancer but the role of prostatic intraepithelial neoplasia (PIN) in the production of total (t) and free (f) PSA is still the subject of research. In this study we wanted to discover whether variations in serum fPSA and tPSA levels are caused by PIN. Material and Methods: We reviewed the medical records of 87 patients: in 32 of them the diagnosis of isolated PIN was made from surgical samples (simple prostatectomy, n = 19; radical cystectomy, n = 13); in 30 patients a diagnosis of benign prostatic hyperplasia (BPH) without PIN or prostatic carcinoma was made after simple prostatectomy (n = 20) or radical cystectomy (n = 10); and in 25 patients a clinically significant prostatic cancer was diagnosed and these patients underwent radical prostatectomy. All patients underwent a standard preoperative evaluation, including serum fPSA and tPSA determinations and PSA density. Results: The frequency of isolated PIN in simple prostatectomy specimens was 6.3%. The mean f/t PSA ratios were 17.66% in the 32 patients with PIN, 19.2% in the 8 patients with low-grade PIN, 17.6% in the 24 patients with high-grade PIN, 24.2% in patients with BPH and 13% in patients who underwent radical prostatectomy. Conclusions: We believe that to make a definitive diagnosis of isolated PIN without carcinoma, study of the whole prostate gland is necessary, in order to definitively exclude the presence of concurrent neoplastic foci. Our data show that PIN does not contribute to tPSA levels and density; however, it may be responsible for a slight reduction in the f/t PSA ratio, with a significant reduction in cases with high-grade PIN (17.6%) compared to those with BPH (24.2%). [ABSTRACT FROM AUTHOR]

Background: Suction techniques showed potential to improve outcomes of retrograde intra-renal surgery (RIRS). We assessed the 24-hour stone-free rate (SFR) and complications after RIRS using flexible and navigable suction ureteral access sheaths (FANS-UAS)., Methods: Sixteen centers prospectively contributed to data (August 2023-October 2023). Inclusion criteria: age ≥18 years, single renal stone, pre and 24-hour post-RIRS CT scan. Exclusion criteria were: ureteral stone, anomalous kidney, multiple stones. SFR was divided into: 1) grade A - no fragments; 2) grade B - fragments ≤2 mm; 3) grade C - fragments 2.1-4 mm; and 4) grade D - fragments >4 mm. A multivariable logistic regression analysis model was performed to assess factors associated with the odds of having grade A stone-free status. Data are expressed as median (interquartile range), absolute numbers and frequencies, odds ratio (OR), and 95% confidence interval (CI)., Results: One hundred forty-two patients with a median age of 52 years (40-61) were enrolled. 61.3% were males. Median stone volume was 1165 mm 3 (656-1936). Median operative time was 48.5 (36.25-71.75) min. Transient fever (37°C-37.5°C) occurred in 10 (7%) patients. No sepsis case occurred. 96.5% of patients were stone-free (Grade A+B). Grade A SFR was 52.8%. All patients were discharged within 48 hours. Bone window (OR 3.156 95% CI 1.177-9.130, P=0.027) was the only factor significantly associated with higher odds of 100% SFR, while stone volume (OR 0.999, 95% CI 0.999-1.000, P=0.007) was significantly associated with lower odds., Conclusions: Imaging and clinical evidence demonstrate excellent perioperative outcomes just 24 hours post RIRS with FANS-UAS. The technique demonstrates a good safety profile, ability for immediate high SFR, and a low rate of infective complications.

Introduction: According to the Urology guidelines, in selected cases of distal upper tract urothelial carcinoma (UTUC) segmental ureterectomy (SU) can be offered. There is no consensus in the surgical technique of preference. Robot-assisted SU could be an option to overcome all the limitations of open and laparoscopic techniques. We describe our first experience of robot assisted SU with psoas hitch ureteral reimplantation (RAPHUR)., Materials and Methods: 11 patients underwent RAPHUR for distal UTUC between 2013 and 2017 in a single centre. Pre-, intra-, and postoperative outcomes were assessed. Conventional imaging was performed after 1, 3, 6 months and 1 year from surgery as follow up protocol. We retrospectively evaluated the technical feasibility, oncological and functional outcomes., Results: Median age was 71 years (57-91). The median length of the ureteral defect was 23 mm (10-40). Median preoperative creatinine level was 1.22 mg/dl (0.7-1.85) and median eGFR was 57.5 ml/min/1.73m2 (31-80). Five (45.5%) patients were symptomatic and 7 (63.6%) had hydronephrosis. Median operative time was 185 min (120-240), with a median blood loss of 100 ml (50-300). No case required conversion to open surgery. Overall, only 1 (9%) patient developed Clavien Dindo ≥ 3 postoperative complications. Average hospital stay was 7 (2-9) days. Mean postoperative creatinine was 1.05 mg/dl (0.8-1.85) and mean postoperative eGFR was 72 (36-83). During a median follow up time of 25.5 months (12-53), 4 (36.4%) patients experienced recurrence of urothelial cancer at conventional imaging follow up and 2 (18.2%) died due to its progression., Conclusions: In our initial experience RAPHUR can be proposed to selected cases of distal ureteral carcinoma with optimal perioperative and functional outcomes. However, cancer control may be undermined compared to nephroureterectomy. Thus, further prospective studies are needed to confirm our findings.

The rising incidence rate of the cancer in the prostate gland has increased the demand for improved diagnostic, imaging, and therapeutic approaches. Prostate-specific membrane antigen (PSMA), with folate hydrolase and carboxypeptidase and, internalization activities, is highly expressed in the epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with, metastasis, progression, and androgen independence. Recently, PSMA has been an active target of investigation by several approaches, including the successful utilization of small molecule inhibitors, RNA aptamer conjugates, PSMA-based immunotherapy, and PSMA-targeted prodrug therapy. Future investigations of PSMA in prostate cancer (PCa) should focus in particular on its intracellular activities and functions. The objective of this contribution is to review the current role of PSMA as a marker for PCa diagnosis, imaging, and therapy.