Abstract BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein ( SPOP ) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations ...across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features ( ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement ( P < .01), and SPOP mutant ( SPOPmut ) cancers had higher rates of CHD1 deletions ( P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
The aim of this study was to compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men.
Dominant ...tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared with 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing.
ERG rearrangement was identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of 101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of 110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%) tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (P = 0.018 and P = 0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P = 0.087, respectively).
Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, whereas ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine whether these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups.
Objective
To provide a summary of our initial experience and assess the impact of the Saline‐Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and oncological ...outcomes after Robot‐Assisted Laparoscopic Radical Prostatectomy (RALP).
Patients and Methods
From January 2021 to July 2022, we included patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and a high probability of extracapsular extension (ECE), ranging from 21% to 73%, as per the Martini et al. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented. The SAFE technique was performed using two approaches, transrectal guided by micro‐ultrasound or transperitoneal. Its principle entails a low‐pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock. Potency was defined as a SHIM score of ≥17 and continence as no pads per day.
Results
At follow‐up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favouring the RALP + SAFE (P = 0.01, P < 0.001, P < 0.001, and P = 0.01, respectively). These results remained significant when the mean SHIM score was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log‐rank P < 0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery.
Conclusions
The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.
Radical prostatectomy (RP) is the most frequent treatment with curative intent performed for prostate cancer to date. Different surgical approaches (perineal, transperitoneal, and extraperitoneal) ...and techniques (laparoscopic and robot assisted) have been described to increase the efficiency and potentially diminish the postoperative complications of this procedure.
The aim of this narrative review is to investigate and define the factors that influence postprostatectomy urinary continence. We highlighted the anatomical landmarks and the modifications of surgical techniques aimed at improving the continence rates and thus, patient quality of life.
After RP, the long-term continence rates range from 84% to 97%. In order to achieve good continence rates, a careful dissection along with meticulous anatomical reconstruction is required. To this end, a detailed knowledge of the periprostatic anatomy is mandatory.
Chromosomal rearrangements account for all erythroblast transformation-specific (ETS) family member gene fusions that have been reported in prostate cancer and have clinical, diagnostic, and ...prognostic implications. Androgen-regulated genes account for the majority of the 5' genomic regulatory promoter elements fused with ETS genes. TMPRSS2-ERG, TMPRSS2-ETV1, and SLC45A3-ERG rearrangements account for roughly 90% of ETS fusion prostate cancer. ELK4, another ETS family member, is androgen regulated, involved in promoting cell growth, and highly expressed in a subset of prostate cancer, yet the mechanism of ELK4 overexpression is unknown. In this study, we identified a novel ETS family fusion transcript, SLC45A3-ELK4, and found it to be expressed in both benign prostate tissue and prostate cancer. We found high levels of SLC45A3-ELK4 mRNA restricted to a subset of prostate cancer samples. SLC45A3-ELK4 transcript can be detected at high levels in urine samples from men at risk for prostate cancer. Characterization of the fusion mRNA revealed a major variant in which SLC45A3 exon 1 is fused to ELK4 exon 2. Based on quantitative PCR analyses of DNA, unlike other ETS fusions described in prostate cancer, the expression of SLC45A3-ELK4 mRNA is not exclusive to cases harboring a chromosomal rearrangement. Treatment of LNCaP cancer cells with a synthetic androgen (R1881) revealed that SLC45A3-ELK4, and not endogenous ELK4, mRNA expression is androgen regulated. Altogether, our findings show that SLC45A3-ELK4 mRNA expression is heterogeneous, highly induced in a subset of prostate cancers, androgen regulated, and most commonly occurs through a mechanism other than chromosomal rearrangement (e.g., trans-splicing).
•There is a great need for the identification of novel biomarkers to predict prostate cancer (PCa) progression to advanced, aggressive disease and also therapeutic response.•Pseudouridine (Ψ), a ...modified nucleoside and isomer of uridine, has repeatedly been seen to hold diagnostic potential for several kinds of cancers, with recent evidence implicating its role in PCa.•This review provides a novel platform for the molecular interrogation of the predictive biomarker value of pseudouridine and its clinical validation for use in human prostate cancer.
Epitranscriptomic analysis has recently led to the profiling of modified nucleosides in cancer cell biological matrices, helping to elucidate their functional roles in cancer and reigniting interest in exploring their use as potential markers of cancer development and progression. Pseudouridine, one of the most well-known and the most abundant of the RNA nucleotide modifications, is the C5-glycoside isomer of uridine and its distinctive physiochemical properties allows it to perform many essential functions. Pseudouridine functionally (a) confers rigidity to local RNA structure by enhancing RNA stacking, engaging in a cooperative effect on neighboring nucleosides that overall contributes to RNA stabilization (b) refines the structure of tRNAs, which influences their decoding activity (c) facilitates the accuracy of decoding and proofreading during translation and efficiency of peptide bond formation, thus collectively improving the fidelity of protein biosynthesis and (e) dynamically regulates mRNA coding and translation. Biochemical synthesis of pseudouridine is carried out by pseudouridine synthases. In this review we discuss the evidence supporting an association between elevated pseudouridine levels with the incidence and progression of human prostate cancer and the translational significance of the value of this modified nucleotide as a novel biomarker in prostate cancer progression to advanced disease.
To provide a systematic summary of prospectively performed studies evaluating ablative therapies for the treatment of prostate cancer (PCa) that included protocol-mandated assessment of (1) residual ...disease by post-treatment biopsy and/or (2) erectile functional outcomes.
We performed a comprehensive literature search in September 2022. Studies were evaluated according to a predefined and registered plan in PROSPERO (CRD42022302777). Only prospective trials with protocol-mandated post-treatment prostate biopsies or functional assessments were included. Targeted focal therapy was the only ablation pattern with sufficient data to perform meta-analyses (29 studies, 1079 patients).
At baseline, 65.0% of patients treated with targeted focal therapy harbored grade group (GG) ≥2 PCa. One year after treatment, in-field treatment failure with ≥GG1 and ≥GG2 PCa occurred in 25.7% (range 11.1%-66.7%) and 8.8% (range 0%-27.8%) of men, respectively. In patients that received whole-gland biopsies 1year after ablation, residual ≥GG1 and ≥GG2 PCa was detected anywhere in the prostate in 43.7% (range 19.4%-71.7%) and 13.0% (range 0%-35.9%) of men. Erectile function was negatively affected by treatment, but 78.7% were potent 1year after targeted focal therapy (7 studies, 197 patients), and the average decrease in erectile function scores was 8.8% at 1year (21 studies, 760 patients).
Though long-term data after targeted focal therapy are limited, oncologic and treatment failure occurred in 13% and 9% (≥GG2 at 6-12months after treatment). Most men were able to maintain potency. This work can help benchmark new techniques and power future trials.
Robot-assisted radical prostatectomy (RARP) is hampered by side effects that may have a serious impact on quality of life, particularly stress urinary incontinence. Continence rates may be improved ...by surgical reconstruction of the pelvic floor.
Video illustrations of different surgical techniques may be particularly worthwhile for practicing urologists in understanding the pelvic-floor anatomy and in the training of residents and fellows in urology.
We describe and video-illustrate commonly performed pelvic reconstructive techniques in RARP, as performed by experts in the field.
Surgical techniques have been described, such as posterior musculofascial reconstruction, anterior reconstruction and periurethral suspension, preservation of membranous urethral lengthening, bladder-neck reconstruction, and combinations.
An overview of continence rates of the different techniques is given.
All reconstructive surgical techniques result in similar short-term continence rates and good-to-excellent outcomes 1yr after surgery. There are only a few randomized clinical trials comparing a reconstructive technique with “no reconstruction” or a different reconstructive technique, and outcomes are conflicting.
Although many of the procedures report a benefit with respect to early continence, benefits seem to diminish with longer follow-up. Whether any of the reconstructive techniques is superior to another is a matter of study.
Early continence rates might be improved by surgical reconstruction of the pelvic floor.
We describe and video-illustrate the most frequently performed pelvic reconstructive techniques in robot-assisted radical prostatectomy aimed at lowering stress urinary incontinence. Many of the procedures report a benefit with respect to early continence, which seems to diminish with longer follow-up.
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