Serum Prostate-specific Antigen Levels Research Articles

Diagnostic and Prognostic Role of Prostate-Specific Antigen Immunologic Staining in Prostate Cancer

Background: Prostatic adenocarcinoma is the second leading cause of death in males due to cancer. The prostate-specific antigen (PSA) serum level is the first marker for screening such patients. Objectives: The present study evaluated the comparison between the degree of staining of the PSA marker and some factors in the prognosis of prostate cancer. Methods: The current cross-sectional study was performed on 97 tissue blocks from patients with prostate adenocarcinoma collected in 2019-2020 from the Pathology Department of Golestan Ahvaz Hospital archives. Clinical information such as age, tumor size, grade of tumor, lymph node involvement, and vascular and perineural invasion was extracted from patients' pathology reports and recorded on a checklist. Then, PSA apical and intensity staining was studied using immunohistochemistry. Results: The mean age of patients was 72.76 ± 8.19 years. The mean serum PSA level was 39.2 ± 8.90. In the present study, the highest PSA staining intensity in the samples was related to grade 1 with a frequency of 39 (40.2%), and then it was related to grade 4 with a frequency of 38 (39.2%), while the lowest frequency of staining intensity was related to grade 2 was with a frequency of 9 (9.3%). Regarding PSA apical staining, 58 samples (59.8%) were positive, and 39 (40.2%) were negative. A statistically significant comparison was shown between Gleason scoring and PSA apical staining (P < 0.001). The results indicate that increasing Gleason scoring decreases the staining intensity, and this correlation is significant (P < 0.05). The mean age in samples with positive staining of apical marker PSA is lower than in samples with negative staining of apical marker PSA but is not statistically significant (P = 0.38). In contrast, the serum level of the PSA marker is statistically significantly higher in samples with positive staining of apical marker PSA than in samples with negative staining of PSA (P < 0.001). According to the Spearman correlation coefficient test, the intensity of staining of the PSA marker decreases with age, and this correlation is significant (P = 0.032). However, according to the Spearman correlation coefficient test, staining intensity increases with increasing serum PSA level, and this correlation is statistically significant (P < 0.001). Conclusions: It is also suggested that in future studies with a larger sample size, the comparison between apical marker expression and PSA marker staining intensity with clinicopathological factors, survival and mortality rates, response to treatment, etc., will be evaluated.

Evaluation of Matrix Metalloproteases by Artificial Intelligence Techniques in Negative Biopsies as New Diagnostic Strategy in Prostate Cancer.

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15-46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients' classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis.

MP09-03 COMPARATIVE STUDY OF SIGNIFICANT CANCER DETECTION IN MAGNETIC RESONANCE IMAGING-TRANSRECTAL ULTRASOUND FUSION IMAGE-GUIDED PROSTATE TARGET BIOPSY AND TRANSPERINEAL TEMPLATE-GUIDED SYSTEMATIC BIOPSY: A 15-CENTER PROSPECTIVE STUDY IN JAPAN

You have accessJournal of UrologyCME1 Apr 2023MP09-03 COMPARATIVE STUDY OF SIGNIFICANT CANCER DETECTION IN MAGNETIC RESONANCE IMAGING-TRANSRECTAL ULTRASOUND FUSION IMAGE-GUIDED PROSTATE TARGET BIOPSY AND TRANSPERINEAL TEMPLATE-GUIDED SYSTEMATIC BIOPSY: A 15-CENTER PROSPECTIVE STUDY IN JAPAN Sunao Shoji, Mayura Nakano, Kazuya Oda, Tatsuo Kano, Tatsuya Umemoto, Masayoshi Kawakami, Masahiro Nitta, Masanori Hasegawa, and Akira Miyajima Sunao ShojiSunao Shoji More articles by this author , Mayura NakanoMayura Nakano More articles by this author , Kazuya OdaKazuya Oda More articles by this author , Tatsuo KanoTatsuo Kano More articles by this author , Tatsuya UmemotoTatsuya Umemoto More articles by this author , Masayoshi KawakamiMasayoshi Kawakami More articles by this author , Masahiro NittaMasahiro Nitta More articles by this author , Masanori HasegawaMasanori Hasegawa More articles by this author , and Akira MiyajimaAkira Miyajima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003224.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective of the present study was to evaluate the usefulness of magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion image-guided prostate target biopsy in detecting biopsy-proven clinically significant prostate cancer (csPC) in a multicenter prospective study. METHODS: Patients with serum prostate specific antigen (PSA) levels ≤ 20 ng/m and suspected prostate cancer on multi-parametric MRI were enrolled from 2020 to 2021. For cancer-suspicious areas, each patient underwent a target biopsy and transperineal template-guided 12-core systematic biopsy. The csPC detection rates between target and systematic biopsies were compared. RESULTS: The study included 400 patients (15 centers). The median age was 69 years (47-85), median PSA was 7.32 ng/mL (1.41-19.98), median prostate volume was 35 cc (7.4-131), median number of target biopsies per patient was 1 (1-4), and median biopsy time was 9 minutes (5-41). CsPC detection rates of patients’ target and systematic biopsies were 59.3% and 49%, respectively (p<0.0001). In the pathological findings of target and systematic biopsy cores, csPC detection (57% vs. 10.4%, p<0.0001), cancer core length (6 mm vs. 3 mm, p<0.0001), and cancer core percent (38% vs. 18%, p<0.0001) were significantly higher in target biopsies than in systematic biopsies. On multivariable logistic regression analysis to predict csPC, age (OR 1.054, P=0.002), PSA value (OR 1.097, p=0.033), PSA density (OR 2.068, p<0.0001), highest PI-RADS category (OR 5.105, p<0.0001), and location of the lesion with highest PI-RADS category (TZ vs. PZ) (OR 0.488, p=0.004) were significant risk factors for detecting csPC. On multivariable logistic regression analysis to predict csPC in patients with PI-RADS categories 2 and 3, PSAD was a significant risk factor for detecting csPC (OR 3.665, p<0.0001). Areas under the receiver operating characteristic curve (AUC) for PSAD was significantly greater than non-discrimination for the detection of csPC in patients with PI-RADS categories 2 and 3 (AUC 0.751, p<0.0001). Using cut-off value: 0.150 ng/mL/cc, sensitivity, specificity, positive predictive value, and negative predictive value for detecting csPC were 92.5%, 45.3%, 41.6%, and 93.5%, respectively. CONCLUSIONS: MRI-TRUS fusion image-guided target biopsy was superior to systematic biopsy in detecting patients with csPC. Using a cut-off value of PSAD would avoid unnecessary biopsies for regions with PI-RADS categories 2 and 3. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e104 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sunao Shoji More articles by this author Mayura Nakano More articles by this author Kazuya Oda More articles by this author Tatsuo Kano More articles by this author Tatsuya Umemoto More articles by this author Masayoshi Kawakami More articles by this author Masahiro Nitta More articles by this author Masanori Hasegawa More articles by this author Akira Miyajima More articles by this author Expand All Advertisement PDF downloadLoading ...

Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

Pseurotin A Validation as a Metastatic Castration-Resistant Prostate Cancer Recurrence-Suppressing Lead via PCSK9-LDLR Axis Modulation.

Metastatic castration-resistant prostate cancer (mCRPC) cells can de novo biosynthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 proved to contribute to mCRPC cell motility since PCSK9 knockdown (KD) in mCRPC CWR-R1ca cells led to notable reductions in cell migration and colony formation. Human tissue microarray results proved a higher immunohistoscore in patients ≥ 65 years old, and PCSK9 proved to be expressed higher at an early Gleason score of ≤7. The fermentation product pseurotin A (PS) suppressed PCSK9 expression, protein-protein interactions with LDLR, and breast and prostate cancer recurrences. PS suppressed migration and colony formation of the CWR-R1ca cells. The progression and metastasis of the CWR-R1ca-Luc cells subcutaneously (sc) xenografted into male nude mice fed a high-fat diet (HFD, 11% fat content) showed nearly 2-fold tumor volume, metastasis, serum cholesterol, low-density lipoprotein cholesterol (LDL-C), prostate-specific antigen (PSA), and PCSK9 levels versus mice fed a regular chow diet. Daily oral PS 10 mg/kg treatments prevented the locoregional and distant tumor recurrence of CWR-R1ca-Luc engrafted into nude mice after primary tumor surgical excision. PS-treated mice showed a significant reduction in serum cholesterol, LDL-C, PCSK9, and PSA levels. These results comprehensively validate PS as an mCRPC recurrence-suppressive lead by modulating the PCSK9-LDLR axis.

FDG PET/CT in a Case of Pure Ductal Adenocarcinoma of the Prostate With Osteolytic Metastases and Normal PSA Level.

Prostatic ductal adenocarcinoma is an uncommon aggressive subtype of prostate carcinoma. It is more likely to present with advanced stage and lower prostate-specific antigen. We describe FDG PET/CT findings in a case of pure prostatic ductal adenocarcinoma with lymph node, bone and lung metastases, normal serum prostate-specific antigen level, and elevated serum carbohydrate antigen 19-9 and carbohydrate antigen 724 levels. The primary tumor, and lymph node and bone metastases were hypermetabolic. All the bone metastases were osteolytic. The multiple lung metastases showed no significant FDG uptake, which may be due to small size.

Significance of extraprostatic extension by Grade Groups 1–3 prostatic carcinoma on needle biopsy

It is rare for extraprostatic extension (EPE) on biopsy to be seen with Grade Groups (GG) 1-3 (Gleason scores 3 + 3 = 6; 3 + 4 = 7; 4 + 3 = 7) prostatic adenocarcinoma, and there is no data whether this finding should be a contraindication for performing radical prostatectomy (RP). Thirty eight cases with GG 1-3 prostatic adenocarcinoma as the highest grade in the case with EPE on biopsy were identified from our consultation files. Highly unfavorable findings at RP were those that if they could have been predicted preoperatively, might have factored into the decision of whether to proceed with surgery. For these purposes, highly unfavorable pathology at RP was defined as either the presence of seminal vesicle invasion or lymph node metastases or GG5 (Gleason score 9-10). Among 37 patients with clinical follow-up data, 18 (49%) received radiation and/or hormonal therapy (RT/HT), 13 patients (35%) either underwent (n = 11) or are planning (n = 2) RP, and 6 patients (16%) received either ablation therapy or active surveillance. Based on the 11 RP pathology reports, 8 were GG2, one GG3 with tertiary pattern 5, and two GG3. Ten cases were reported to have EPE and six cases had positive margins. Only one had highly unfavorable pathology with pT3bN1 disease. The only difference between the RP and the RT/HT groups in their pretreatment parameters was the mean age of the RP patients was 61 compared with 69 for the RT/HT men (p = 0.02); the lack of many cases with highly unfavorable pathology at RP cannot be attributable to a selection bias of men with lower volume cancer on biopsy or lower serum prostate-specific antigen levels choosing RP over RT/HT. Despite EPE on biopsy, most men do not have highly unfavorable pathology at RP, and this treatment should remain an option in this setting.

The relationship between serum albumin and prostate-specific antigen: A analysis of the National Health and Nutrition Examination Survey, 2003-2010.

Previous studies have shown that serum albumin is associated with prostate cancer (PCa), but not with prostate-specific antigen (PSA) levels in populations without PCa history. Therefore, we analyzed secondary data provided by the National Health and Nutrition Examination Survey (NHANES) (2003-2010). In total, 5,469 participants were selected from the NHANES database (2003-2010). Serum albumin and PSA levels were serially considered independent and dependent variables, serially. A number of covariates were included in this study, including demographic, dietary, physical examination, and comorbidity data. Using weighted linear regression model and smooth curve fitting, the linear and non-linear relationship between serum albumin and PSA was investigated. After modulating underlying interference factors, the weighted multivariate linear regression analysis revealed that serum albumin did not independently predict PSA levels (β = -0.009 95%CI: -0.020, 0.002). Nevertheless, a non-linear relationship was found between serum albumin and PSA, with a point of 41 g/L. Left of the inflection point, the effect size, 95%CI, and P-value were 0.019 (log2 transformation) (-0.006, 0.043) and 0.1335, respectively. We found a negative association between serum albumin and PSA on the right side of the inflection point, with effect size, 95%CI, and a P-value of -0.022 (log2 transformation) (-0.037, -0.007), 0.0036. In summary, serum albumin and PSA levels are not linearly related. When serum albumin levels exceed 41 g, serum albumin levels are negatively associated with PSA levels.

Prostate-specific antigen density as the best predictor of low- to intermediate-risk prostate cancer: a cohort study.

Evaluation of prostate cancer (PCa) when serum prostate-specific antigen (PSA) level is vaguely elevated is complicated. This is because serum PSA levels only reflect the number of prostate epithelial cells. We aimed to compare PSA and various prostate volume-related factors to determine which one can best predict PCa in patients with a PSA level of 2.5-20 ng/mL. Patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy at the Inje University Sanggye Paik Hospital between January 2018 and July 2021 and who had a PSA level of 2.5-20 ng/mL were retrospectively identified (n=275). Among them, based on biopsy results, patients were divided into cancer group and non-cancer groups, and age, PSA, total prostate volume (TPV), peripheral zone volume (PZV), peripheral zone PSA density (PZ-PSAD), transitional zone-PSAD (TZ-PSAD), and PSAD were compared and analyzed using receiver operating characteristic (ROC) and univariate analyses. The areas under ROC curves (AUCs) for age, total PSA, TPV, PZV, PZ-PSAD, TZ-PSAD, and PSAD for predicting PCa in patients with a PSA level of 2.5-20.0 ng/mL were 0.678, 0.680, 0.671, 0.639, 0.731, 0.736, and 0.764, respectively. In univariate and multivariate analysis, all categorical variables were divided based on the cut-off value and used to predict PCa. Those with a PSAD of ≥0.218 ng/mL2 were found to be at an increased risk of PCa than those with a PSAD of <0.218 ng/mL2 [odds ratio (OR) =3.51; 95% confidence interval (CI): 1.306-9.415], which was the best result, followed by TZ-PSAD with a cut-off value of 0.353. At a PSAD level of 0.218 ng/mL2, 85.0% of the PCa group could avoid unnecessary biopsy and 61.4% of the non-PCa group could reduce missed diagnosis when the TRUS findings were inaccurate. PSAD may inform biopsy decisions as the best predictor of PCa when TRUS findings are ambiguous in patients with a PSA level of 2.5-20.0 ng/mL.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. The mean age of the patients was 66.1±9.3 with a median PSA of 7.5ng/ml. After the treatment, PSA nadir was 4.06±3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12monthsMR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor)

BackgroundThe prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs)....

(18F)-PSMA-1007PET/CT in patients with biochemical recurrence after radical prostatectomy: Diagnostic performance and impact on treatment management.

To evaluate the diagnostic performance of (18F)-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy and the effect of (18F)-PSMA-1007 PET/CT on treatment strategy. A total of 114 patients with BCR after radical prostatectomy who performed (18F)-PSMA-1007 PET/CT were retrospectively analyzed. The Gleason scores (GS), maximum standardized uptake values (SUVmax) and the diagnostic performance were compared according to different prostate-specific antigen (PSA) groups. To evaluate the impact of (18F)-PSMA-1007 PET/CT on treatment management, we also collected subjects' therapy before and after PET/CT. The PSA value was monitored to evaluate the biochemical response. (18F)-PSMA-1007PET/CT was positive in 92/114 patients (80.7%). The detection rates were 20/34 (58.8%), 13/17 (76.5%), 15/17 (88.2%) and 44/46 (95.7%) for PSA levels of 0.2-<0.5, 0.5-<1, 1-<2, ≥2ng/ml. The positive lesions on PET/CT revealed local recurrence in 24/114 (21.1%) patients, lymph nodes metastases in 54/114 (47.4%) and metastatic sites in bone, lung, and others in 75/114 (65.8%). A significant positive correlation was observed between the GS/ SUVmax and PSA level (r1=0.375, r2=0.336, P<0.001). As a result of the (18F)-PSMA-1007 PET/CT, therapeutic decision-making changed in 60/114 (52.6%) patients. With a follow-up of 11.0±6.4 months, 81/114 PSA were collected after treatment guided by (18F)-PSMA-1007 PET/CT, and in 42/81 (51.9%) of patients, serum PSA levels decreased of more than 60%. (18F)-PSMA-1007 PET/CT has a high lesion detection rate for recurrent prostate cancer (PCa) and could have significant implications in decision-making treatment plan for the majority of PCa patients.

Vitamin D, a Regulator of Androgen Levels, Is Not Correlated to PSA Serum Levels in a Cohort of the Middle Italy Region Participating to a Prostate Cancer Screening Campaign.

Prostate cancer (PCa) is the most common non-cutaneous malignancy in men worldwide, and it represents the fifth leading cause of death. It has long been recognized that dietary habits can impact prostate health and improve the benefits of traditional medical care. The activity of novel agents on prostate health is routinely assessed by measuring changes in serum prostate-specific antigen (PSA) levels. Recent studies hypothesized that vitamin D supplementation reduces circulating androgen levels and PSA secretion, inhibits cell growth of the hormone-sensitive PCa cell lines, counteracts neoangiogenesis and improves apoptosis. However, the results are conflicting and inconsistent. Furthermore, the use of vitamin D in PCa treatments has not achieved consistently positive results to date. In order to assess the existence of a correlation between the PSA and 25(OH)vitamin D levels as widely hypothesized in the literature, we analyzed the serum PSA and 25(OH)vitamin D concentration on a cohort of one hundred patients joining a PCa screening campaign. Additionally, we performed medical and pharmacological anamnesis and analyzed lifestyle, as sport practice and eating habits, by administering a questionnaire on family history. Although several studies suggested a protective role of vitamin D in PCa onset prevention and progression, our preliminary results revealed a clear absence of correlation between the serum vitamin D and PSA concentration levels, suggesting that vitamin D has no impact on PCa risk. Further investigations enrolling a huge number of patients are needed with particular attention to vitamin D supplementation, calcium intake, solar radiation that influences vitamin D metabolism and other potential indicators of health to confirm the absence of correlation observed in our study.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Impact of 18 F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy.

We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.

Cervical lymphadenopathy as initial presentation of metastatic prostate cancer: A retrospective study of five cases and literature review.

Cervical lymphadenopathy as the initial presentation of metastatic prostate cancer is particularly uncommon, and easily misdiagnosed. In the current study, we describe five cases of metastatic prostate cancer in our hospital that presented with cervical lymphadenopathy as an initial symptom. The diagnosis was confirmed by needle biopsy of the suspicious lymph nodes and the serum prostate specific antigen (PSA) levels of all patients exceeded 100 ng/ml. The five patients were treated with hormonal therapy; four received traditional hormonal therapy, including bicalutamide and goserelin; one patient received hormonal therapy that included abiraterone and goserelin. Case 1 developed into castration-resistant prostate cancer (CRPC) after 7 months and died after 12 months. Case 2 rejected regular hormonal therapy for personal reasons and died 6 months after the initial diagnosis. Case 3 was still alive at the time of writing. Case 4 was administered with abiraterone, prednisolone and goserelin; the treatment was effective and the patient has remained symptom-free for the last 24 months. Case 5 was treated with hormonal and chemotherapy but died 8 months after diagnosis. In conclusion, any elderly male presenting with cervical lymphadenopathy should be considered the possibility of prostate cancer, especially when the needle biopsy reveals adenocarcinoma. The prognosis for patients presented with cervical lymphadenopathy as the initial presentation is usually poor. Hormone therapy based on abiraterone may yield a better response in such cases.

Urinary extracellular vesicles miRNA-A new era of prostate cancer biomarkers.

Prostate cancer is the second most common male cancer worldwide showing the highest rates of incidence in Western Europe. Although the measurement of serum prostate-specific antigen levels is the current gold standard in PCa diagnosis, PSA-based screening is not considered a reliable diagnosis and prognosis tool due to its lower sensitivity and poor predictive score which lead to a 22%-43% overdiagnosis, unnecessary biopsies, and over-treatment. These major limitations along with the heterogeneous nature of the disease have made PCa a very unappreciative subject for diagnostics, resulting in poor patient management; thus, it urges to identify and validate new reliable PCa biomarkers that can provide accurate information in regard to disease diagnosis and prognosis. Researchers have explored the analysis of microRNAs (miRNAs), messenger RNAs (mRNAs), small proteins, genomic rearrangements, and gene expression in body fluids and non-solid tissues in search of lesser invasive yet efficient PCa biomarkers. Although the presence of miRNAs in body fluids like blood, urine, and saliva initially sparked great interest among the scientific community; their potential use as liquid biopsy biomarkers in PCa is still at a very nascent stage with respect to other well-established diagnostics and prognosis tools. Up to date, numerous studies have been conducted in search of PCa miRNA-based biomarkers in whole blood or blood serum; however, only a few studies have investigated their presence in urine samples of which less than two tens involve the detection of miRNAs in extracellular vesicles isolated from urine. In addition, there exists some discrepancy around the identification of miRNAs in PCa urine samples due to the diversity of the urine fractions that can be targeted for analysis such as urine circulating cells, cell-free fractions, and exosomes. In this review, we aim to discuss research output from the most recent studies involving the analysis of urinary EVs for the identification of miRNA-based PCa-specific biomarkers.

Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis

Prostate cancer remains one of the most fatal malignancies in men in the United States. Predicting the course of prostate cancer is challenging given that only a fraction of prostate cancer patients experience cancer recurrence after radical prostatectomy or radiation therapy. This study examined the expressions of 14 fusion genes in 607 prostate cancer samples from the University of Pittsburgh, Stanford University, and the University of Wisconsin-Madison. The profiling of 14 fusion genes was integrated with Gleason score of the primary prostate cancer and serum prostate-specific antigen level to develop machine-learning models to predict the recurrence of prostate cancer after radical prostatectomy. Machine-learning algorithms were developed by analysis of the data from the University of Pittsburgh cohort as a training set using the leave-one-out cross-validation method. These algorithms were then applied to the data set from the combined Stanford/Wisconsin cohort (testing set). The results showed that the addition of fusion gene profiling consistently improved the prediction accuracy rate of prostate cancer recurrence by Gleason score, serum prostate-specific antigen level, or a combination of both. These improvements occurred in both the training and testing cohorts and were corroborated by multiple models.

Overexpression of YTHDC2 contributes to the progression of prostate cancer and predicts poor outcomes in patients with prostate cancer.

YTH domain-containing protein 2 (YTHDC2), a member of N6-methyladenosine (m6A) readers, has been reported to be closely associated with multiple cancer types. However, very little is known about the YTHDC2 gene and its involvement in prostate cancer. YTHDC2 protein expression level was analyzed and correlated to clinical outcomes in prostate cancer patients who underwent prostatectomy in Guizhou Provincial People's Hospital. The YTHDC2 expression level was also detected in prostate cancer cell lines and an immortalized prostate epithelial cell line BPH-1 and RWPE1 by quantitative real-time reverse transcription polymerase chain reaction. Furthermore, we established stable cell lines (DU145 and PC-3) transfected with either empty vector or the full-length YTHDC2 gene and conducted cell function assays in vitro. Fisher's exact test and Pearson χ2 test were employed, Kaplan-Meier method was used for the survival analysis. Of 32 patient samples who enrolled in this study, YTHDC2 was significantly upregulated in prostate cancer (PCa) patients with higher Gleason scores and serum prostate-specific antigen levels. YTHDC2 expression was significantly elevated in all PCa cell lines compared to BPH-1 and RWPE1 (all p < 0.05). Functionally, the enforced expression of YTHDC2 markedly promoted cell growth, migration, and invasion efficacies in prostate cancer cells. Our data indicate that YTHDC2 upregulation may be potentially associated with the prognosis of prostate cancer patients.

Hepatic Small Vessel Neoplasm Mimics Prostate Cancer on 18 F-DCFPyl PET/CT.

18 F-DCFPyl is a Food and Drug Administration-approved radiotracer that targets prostate-specific membrane antigen and is used in the detection of recurrent or metastatic prostate cancer. As its use has increased, a growing number of nonprostatic disease entities have been identified that express prostate-specific membrane antigen and can mimic prostate cancer. Thus, the interpreting physician must also consider other variables such as serum prostate-specific antigen levels and the distribution of uptake to avoid an inappropriate diagnosis of metastatic prostate cancer. We describe 18 F-DCFPyl uptake associated with a hepatic small vessel neoplasm, an association previously undescribed in the literature.