Prostate Carcinoma Research Articles

A pictorial view on false positive findings of 68Ga-PSMA-11 PET/CT and their prognostic value in patients with prostate carcinoma after radical prostatectomy and undetectable PSA values.

Recently, gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) has become a key imaging method in prostate carcinoma staging and biochemical progression, with varying sensitivities in different studies (from 40% to 80%). After four years of experience with 68Ga-PSMA-11 PET/CT, we found that it is possible to detect lesions with increased PSMA expression in patients with undetectable prostate specific antigen (PSA) levels after radical prostatectomy. The key questions we wanted to answer were as follows: if those lesions were malignant and could the early detection of those malignant lesions have a role in patient management? We aimed to identify and follow up PSMA-positive findings for a period of 4 years in patients with prostate cancer after radical prostatectomy and undetectable PSA values at the time of the examination. We also explored false-positive lesions in detail. The study included all patients who underwent radical prostatectomy and had undetectable PSA values <0.05ng/mL and who underwent 68Ga-PSMA-11 PET/CT between July 2019 and December 2019. We performed 220 studies and found 40 patients with these characteristics; these patients were included in this study. All of them were followed up until July 2023. Any finding with increased radiopharmaceutical accumulation above the background activity in the respective area was considered a false positive. Prostate-specific membrane antigen accumulation in established lesions was assessed semi-quantitatively by the maximum standardized uptake value (SUVmax) and qualitatively by the four-point visual scale proposed in the E-PSMA recommendations. We found 15/40 (37.5%) patients with PSMA-positive findings. These were predominantly bone changes without a corresponding CT abnormality or discrete cystic or osteoblastic lesions with above-background increased PSMA expression. The mean SUVmax of these non-specific lesions was 3.02 (SD 2.86). After 3.5-4 years of follow-up, biochemical progression was found in only two of the patients.The great sensitivity of the method nowadays is a powerful engine for the development of new therapeutic options. On the other side, the lower specificity due to false positive findings, if misinterpreted, might lead to switching to a higher stage, with the planned radical treatment replaced by palliative treatment. The presence of 68Ga-PSMA-11 PET/CT-positive findings in patients after radical prostatectomy and an undetectable PSA had a low predictive value for future progression. The interpretation of 68Ga-PSMA-11 PET/CT should always include a complex assessment of the clinical setting-the risk group, PSA value and degree of PSMA accumulation in the lesions. In these situations, further clarification of PSMA-positive findings is appropriate before deciding to change treatment.

A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer

BackgroundClinical manifestation of prostate cancer (PCa) is highly variable. Aggressive tumors require radical treatment while clinically non-significant ones may be suitable for active surveillance. We previously developed the prognostic ProstaTrend RNA signature based on transcriptome‐wide microarray and RNA-sequencing (RNA-Seq) analyses, primarily of prostatectomy specimens. An RNA-Seq study of formalin-fixed paraffin-embedded (FFPE) tumor biopsies has now allowed us to use this test as a basis for the development of a novel test that is applicable to FFPE biopsies as a tool for early routine PCa diagnostics.MethodsAll patients of the FFPE biopsy cohort were treated by radical prostatectomy and median follow-up for biochemical recurrence (BCR) was 9 years. Based on the transcriptome data of 176 FFPE biopsies, we filtered ProstaTrend for genes susceptible to FFPE-associated degradation via regression analysis. ProstaTrend was additionally restricted to genes with concordant prognostic effects in the RNA-Seq TCGA prostate adenocarcinoma (PRAD) cohort to ensure robust and broad applicability. The prognostic relevance of the refined Transcriptomic Risk Score (TRS) was analyzed by Kaplan–Meier curves and Cox-regression models in our FFPE-biopsy cohort and 9 other public datasets from PCa patients with BCR as primary endpoint. In addition, we developed a prostate single-cell atlas of 41 PCa patients from 5 publicly available studies to analyze gene expression of ProstaTrend genes in different cell compartments.ResultsValidation of the TRS using the original ProstaTrend signature in the cohort of FFPE biopsies revealed a relevant impact of FFPE-associated degradation on gene expression and consequently no significant association with prognosis (Cox-regression, p-value > 0.05) in FFPE tissue. However, the TRS based on the new version of the ProstaTrend-ffpe signature, which included 204 genes (of originally 1396 genes), was significantly associated with BCR in the FFPE biopsy cohort (Cox-regression p-value < 0.001) and retained prognostic relevance when adjusted for Gleason Grade Groups. We confirmed a significant association with BCR in 9 independent cohorts including 1109 patients. Comparison of the prognostic performance of the TRS with 17 other prognostically relevant PCa panels revealed that ProstaTrend-ffpe was among the best-ranked panels. We generated a PCa cell atlas to associate ProstaTrend genes with cell lineages or cell types. Tumor-specific luminal cells have a significantly higher TRS than normal luminal cells in all analyzed datasets. In addition, TRS of epithelial and luminal cells was correlated with increased Gleason score in 3 studies.ConclusionsWe developed a prognostic gene-expression signature for PCa that can be applied to FFPE biopsies and may be suitable to support clinical decision-making.

Synchronous advanced prostate and colonic adenocarcinoma as the first presentation of Lynch syndrome: a case report

Synchronous advanced prostate and colonic adenocarcinoma as the first presentation of Lynch syndrome: a case report

Microboost dose escalation for localized prostate cancer within a statewide radiation oncology quality consortium.

298 Background: The phase III FLAME trial demonstrated that in localized prostate cancer, an external beam radiotherapy (EBRT) simultaneous integrated microboost to an MRI-defined dominant intraprostatic lesion improves biochemical control without affecting toxicity and quality of life. Given the complexity required to deliver high microboost doses, we hypothesized that practice patterns are variable in clinical practice. We aimed to characterize microboost utilization and evaluate dosimetric parameters within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Methods: Men with intermediate or high-risk prostate adenocarcinoma treated with curative intent radiotherapy for intact disease were included. Data was prospectively collected, including T/N-category, Gleason score, prostate-specific antigen, and percent positive biopsy cores. Full DICOM files were available for dosimetric data. Multivariable analyses (MVA) were used to evaluate associations between receipt of microboost, known prognostic factors, and fiducial marker and rectal spacer placement (advanced image guided radiation therapy (IGRT)). Results: From 10/26/20 to 06/26/23, 741 patients across 26 centers were enrolled, 71% (n=528) with intermediate-risk and 29% (n=213) with high-risk disease. Androgen deprivation therapy was planned in 61%. EBRT + whole-gland brachytherapy boost was utilized in 29% (n=217/741) of patients. Of those treated with EBRT (71%, n=524/741), 10% received a microboost (n = 53/524). Brachytherapy boost and microboost were used in 9 and 7 centers, respectively. Most patients received either conventional fractionation or moderate hypofractionation- 11% and 66% in EBRT without microboost and 21% and 60% with microboost, respectively. Microboost treatment was associated with use of a planning MRI (91% vs. 62%, p &lt;0.0001) as well as fiducial marker and rectal spacer placement (76% vs. 45%, p &lt;0.0001). Median prostate planning target volume (PTV) was smaller in microboost patients (127 cc vs. 91 cc, p = 0.002); median boost volume was 21 cc. Median boost dose (D0.1cc) was 117% (IQR 115% – 119%) of the PTV prescription. Microboost patients had significantly higher mean bladder D1cc[%] (105.7% vs. 103.4%, p = 0.002) and numerically lower rectal D1cc[%] (90.7% vs. 94.1%, p = 0.065). On MVA, receipt of microboost was significantly associated with grade group 4 or 5 disease, planning MRI use, and fiducial and rectal spacer use. Conclusions: Within a large, diverse prospective cohort of men with prostate cancer treated in both academic and community settings, a microboost was utilized in 10% of EBRT cases. Microboost use was associated with higher grade group, MRI planning, and advanced IGRT. EBRT microboost is an emerging dose escalation strategy and further studies confirming safety and improved clinically meaningful outcomes may increase uptake in routine practice.

A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR)

BackgroundDespite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer.MethodsThis is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS).DiscussionOur prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients.Trial registrationClinicalTrials.gov: NCT06059014.

Survival outcomes of metastatic prostate adenocarcinoma by primary metastatic site: A Surveillance, Epidemiology, and End Results (SEER) database study.

Survival outcomes of metastatic prostate adenocarcinoma by primary metastatic site: A Surveillance, Epidemiology, and End Results (SEER) database study.

Phase II study of pembrolizumab in combination with radiation with or without olaparib in localized high-risk prostate cancer.

TPS351 Background: Definitive radiation therapy (DRT) combined with androgen deprivation therapy (ADT) remains the standard of care in patients with high-risk prostate cancer (HRPC) who do not want surgery. However, up to 50% experience biochemical recurrence (BCR) within 5 years. A phase 3 NCIC group reported the 10-year biochemical recurrence free survival was 63% in ADT plus DRT vs. 27% in ADT alone. There is an urgent need for effective novel combination strategies. We hypothesize combined immune sensitizing effects of PARPi and radiation will result in significant activity of immunotherapy in men with HRPC. Methods: This is a multicenter phase II randomized study to assess biochemical response rates, safety and tolerability of combined therapy in pts with localized HRPC who elected for concurrent DRT. A total of 64 pts will be randomized 1:1 to receive either pembrolizumab (P) combined with olaparib or single agent P in addition to the standard of care ADT with DRT. Hypofractionated IMRT (2.4 to 4 Gy per fraction over 4-6 weeks) will be delivered and all pts will receive adjuvant P for one year and ADT for at least 18 months. All pts will undergo germline testing. Key eligible criteria include biopsy confirmed prostate adenocarcinoma who meets at least one of the four high-risk features: 1) clinical T3a, T3b or T4, 2) N1, 3) Gleason grade group 4 or 5, and 4) PSA &gt;20 ng/ml. Patients with less than 2 cm pelvic nodes and received ADT therapy within 3months prior to study enrollment are allowed. PSA &gt;150 ng/ml and patients with distant metastases will be excluded. The primary endpoint is to assess the proportion of patients who achieve a PSA nadir level of ≤ 0.06 ng/ml within six months after completion of radiation therapy in each arm. The secondary objectives include safety/tolerability, BCR and metastasis-free survival at 3 years. BCR is defined by the Phoenix definition. The study is designed to detect a 15% improvement in PSA nadir ≤ 0.06 ng/mL within 6 months after completion of the combined therapy versus historical control group data Geara FB et al., 2017. Enrollment began in August 2023. Clinical trial information: NCT05568550 .

Novel Prostate Biopsy Technique Using Imaging Fusion in a Patient With Absent Rectum

OBJECTIVETo describe a novel technique using pre-operative multi-parametric prostate MRI and intraoperative CT 3D/3D fusion for systematic and targeted prostate biopsy in a patient lacking a rectum. METHODSA 70-year-old male with prior total colectomy for ulcerative colitis was referred for elevated PSA (8.01) with PIRADS 4 lesion on MRI. Under general anesthesia, an ultra-low-dose (ULD) cone beam CT was performed in supine position using a robotic-armed fluoroscopy system (Artis Zeego Care+Clear™, Siemens). 3D/3D auto-registration of the femoral heads and prostate from the MRI and ULD CT was performed. The prostate edges and two areas of concern were marked. Then, reduced-dose fluoroscopy-guided prostate biopsy was performed transperineally using triangulation technique. RESULTS27 prostate biopsy cores were obtained. Grade group 5 (Gleason 4+5=9) prostate cancer was identified in two cores from the targeted lesion and one core from the prostate base. The remaining twenty-four biopsies were negative for malignancy. Surgical time was 81 minutes. PSMA scan demonstrated no metastasis or lymphadenopathy. Robotic-assisted laparoscopic radical prostatectomy was performed without complications. Final pathology demonstrated T3a, grade group 5 prostate adenocarcinoma involving 10% of the prostate volume with negative surgical margins. CONCLUSIONSThis is the initial report of fluoroscopy-guided prostate biopsy using imaging fusion techniques in a patient without a rectum. This technique allowed precise identification of localized, very high-risk prostate cancer with over three times the number of cores, and much lower radiation dose, than typical CT-guided biopsies. Our technique could provide a new paradigm in targeted prostate biopsy.

Comparative effectiveness of ChatGPT 4.0 and medical oncologists in telemedicine-based management of metastatic prostate carcinoma (mPC).

226 Background: The advent of telemedicine, accentuated during the COVID-19 pandemic, offers a prospective modality, especially when synergized with artificial intelligence (AI) tools such as ChatGPT 4.0. In this investigation, we sought to investigate the proficiency of ChatGPT vs. medical oncologists in the telemedicine-centric management of mPC. Methods: This IRB-approved retrospective study compared the competencies of ChatGPT and oncologists in conducting telemedicine consultations for patients with mPC. Out of 975 patients screened between April 1, 2022, and March 30, 2023, 102 met the inclusion criteria of having a diagnosis of mPC, attending at least one telemedicine consultation during the specified period, and having documentation available for two consecutive visits to enable the analysis of treatment decisions and outcomes. ChatGPT was asked to pre-chart and determine if a face-to-face consultation is needed. Its clinical competence was assessed using miniCEX, and medical decision-making (MDM). The Cohen's kappa test was used to measure the level of agreement between ChatGPT and oncologists in treatment decisions, and the Mann-Whitney U test was used to compare miniCEX and MDM. Results: The majority of patients were White (97.06%), with a median age of 75 years (range:53 to 99). Nearly all patients were diagnosed with adenocarcinoma (96.08%), with a median Gleason score of 7 (range: 6 to 10). The prevalent metastatic sites were bone (47.4%) and lymph nodes (44.16%). 26.88% had an ECOG score of 0, 54.84% had a score of 1, and 18.28% had a score greater than 1. Common coexisting conditions included diabetes mellitus (11.11%), hypertension (29.82%), hyperlipidemia (24.56%), and depression (7.6%). The primary outcome measured the concordance between ChatGPT and oncologists on whether to continue or cease the current treatment There was a statistical significance in sensitivity and specificity between clinicians and ChatGPT (Chi-squared=5.1, p=0.02). Cohen's Kappa showed a moderate concordance (Kappa = 0.43, p&lt;0.001). There was no difference in the number of diagnoses made by the two parties (p=0.13 and 0.06, respectively). ChatGPT's median miniCEX score was 8 (SD=0.59), and its median MDM length was 41 words (SD=6.06). The average time saved by ChatGPT in pre-charting was 41 minutes (SD=6). Conclusions: ChatGPT showed moderate concordance with oncologists for the management of mPC in telemedicine. Subsequent investigations are needed to explore its potential in healthcare.

Physiological 68Ga-PSMA-11 Uptake in Dural Venous Sinuses.

We describe hitherto unreported physiological low-grade 68Ga-PSMA-11 uptake in dural sinuses of patients who underwent 68Ga-PSMA-11 PET/CT for evaluation of prostate carcinoma. A strong positive correlation was found between SUVmax of tracer uptake in dural sinuses and SUVmax of blood pool activity in superior vena cava. Low-grade 68Ga-PSMA-11 uptake seen in dural sinuses is physiological and is most likely result of venous blood pool activity. Such uptake should not be interpreted as pathological. Knowledge of such physiological uptake is essential for optimal interpretation of PSMA PET/CT images and differentiating physiological versus pathological uptake.

Prospective randomized study correlating intra-operative urethral mucosal injury with early period after transurethral resection of the prostate stricture urethra: A novel concept

ObjectiveTo investigate the incidence of urethral stricture during the early period after transurethral resection of the prostate (TURP) and correlate its incidence with intra-operative urethral mucosal injury during TURP. Also to compare the other established risk factors affecting the development of urethral stricture among patients undergoing monopolar or bipolar TURP over a period of 6 months follow-up as the prospective randomized study. MethodsOne hundred and fifty men older than 50 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia were randomized to undergo either standard monopolar TURP with glycine as the irrigation fluid or bipolar TURP with normal saline as irrigant. The prostate size, operative time, intra-operative mucosal rupture, catheter time, catheter traction duration, uroflowmetry, and post-operative stricture rate were compared. ResultsA total of 150 patients underwent TURP, including 74 patients undergoing monopolar TURP (one patient was excluded as his post-operative histopathological examination report was of adenocarcinoma prostate) and 75 patients undergoing bipolar-TURP, all of which were performed using a 26 Fr sheath resectoscope. The mean International Prostate Symptom Score and maximum urinary flow rate score at post-operative 3 months and 6 months were comparable between the groups. Out of 149 patients, nine patients (6.0%) developed urethral stricture. The severity of the injury (urethral mucosal injury) correlated with the likelihood of developing a subsequent complication (stricture urethra). Patients with stricture had significantly larger prostate volume than patients without stricture (65.0 mL vs. 50.0 mL; p=0.030). Patients with stricture had longer operative time than patients without stricture (55.0 min vs. 40.0 min; p=0.002). In both procedures, formation of post-operative stricture urethra was independently associated with intra-operative mucosal injury. ConclusionIntra-operative recognition of urethral mucosal injury helps in prediction of stricture urethra formation in early post-operative period.

Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs

Combination therapy is a fundamental strategy in cancer chemotherapy. It involves administering two or more anti-cancer agents to increase efficacy and overcome multidrug resistance compared to monotherapy. However, drug combinations can exhibit synergy, additivity, or antagonism. This study presents a machine learning framework to classify and predict cancer drug combinations. The framework utilizes several key steps including data collection and annotation from the O’Neil drug interaction dataset, data preprocessing, stratified splitting into training and test sets, construction and evaluation of classification models to categorize combinations as synergistic, additive, or antagonistic, application of regression models to predict combination sensitivity scores for enhanced predictions compared to prior work, and the last step is examination of drug features and mechanisms of action to understand synergy behaviors for optimal combinations. The models identified combination pairs most likely to synergize against different cancers. Kinase inhibitors combined with mTOR inhibitors, DNA damage-inducing drugs or HDAC inhibitors showed benefit, particularly for ovarian, melanoma, prostate, lung and colorectal carcinomas. Analysis highlighted Gemcitabine, MK-8776 and AZD1775 as frequently synergizing across cancer types. This machine learning framework provides a valuable approach to uncover more effective multi-drug regimens.

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images.

Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.

Enlarged Cervical Lymph Nodes as a First Presentation of Metastatic CA Prostate

Prostate cancer is one of the common cancers in the world. It often metastasizes to the regional lymph nodes, bones, lungs, pleura, liver, and adrenal glands but metastasis to supraclavicular lymph nodes is very uncommon. Cervical lymph node metastasis as the first clinical manifestation of the prostate carcinoma has been reported only a few times till date. We present an unusual case of a 70- year old male who presented with enlarged swellings on the left side of his neck and was diagnosed with carcinoma prostate.

Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway

Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.

Cerebral and Muscular Metastases From Prostate Adenocarcinoma Initially Depicted by 177 Lu-PSMA SPECT/CT.

Cerebral and muscular metastases from prostatic adenocarcinoma occur rarely. Patients who develop such metastatic pattern exhibit noticeable symptoms. Herein, we present a 68-year-old man diagnosed with metastatic castrate-resistant prostate cancer. The patient received multiple 177 Lu-PSMA cycles. After the last cycle, a posttreatment SPECT/CT suggested disease progression with uncommon metastatic pattern in the right temporal brain lobe and muscles. 68 Ga-PSMA PET/CT and brain MRI confirmed these findings. Surprisingly, the patient remained asymptomatic up until the conclusion of the follow-up, which lasted for 3 months. This case emphasizes the importance of posttreatment scintigraphic imaging when other biomarkers are inconclusive.

Bilateral Subcapsular Orchidectomy as Surgical Castration: A Reasonable Aesthetic Alternative to Bilateral Total Orchidectomy in Patients with Metastatic Hormone-sensitive Prostate Cancer

Background: The study highlights the historical significance of bilateral orchidectomy as the traditional 'gold standard' for surgical androgen deprivation in treating advanced prostate cancer. The study presented aims to compare total orchidectomy and subcapsular orchidectomy, considering factors such as androgen ablation, disease progression control, and patient satisfaction. Objective: This study aims to compare the effectiveness and patient satisfaction of bilateral subcapsular orchidectomy and bilateral total orchidectomy treatment in managing hormone-sensitive metastatic prostate cancer. Methods and materials: In this prospective study of 18 months at North East Medical College Hospital, 40 participants with Metastatic Carcinoma of Prostate underwent bilateral orchidectomy, among them 20 subcapsular and 20 total orchidectomy. The research focused on evaluating the impact of these treatments on serum testosterone levels, serum PSA levels, employing as outpatient procedures and a 3-month follow-up, utilizing a satisfaction scoring scale. Data, including age, Gleason Grade Group, PSA, and testosterone levels at diagnosis &amp; at 3-month follow-up were recorded and analyzed using IBM SPSS-21 software. Result: The study compared Bilateral Subcapsular Orchidectomy and Bilateral Simple Orchidectomy for Hormone-Sensitive Metastatic Carcinoma of Prostate in 40 patients. The highest frequency was in the 71-75 age group (30%), with a mean age of 66.67 ± 2.21 years. Gleason grade group 3 dominated (40%), followed by 2 (25%). Pre-operative PSA levels were 31.14±1.27 ng/ml for Subcapsular and 35.21±1.70 ng/ml for Total Orchidectomy, decreasing post-operatively to 8.25±0.41 ng/ml and 7.32±0.80 ng/ml, respectively. Pre-operative testosterone levels were 513.21±3.01 ng/dl for Subcapsular and 498.40±2.10 ng/dl for Total Orchidectomy, decreasing post-operatively to 21.14±2.84 ng/dl and 16.90±1.08 ng/dl, respectively, with non-significant p-values. Surgery related Satisfaction scores in the Follow-Up phase were significantly higher for Subcapsular Orchidectomy, 2.91±0.31 comparing with Total Orchidectomy, 2.05±0.45. The results emphasize better patient satisfaction after subcapsular orchidectomy, while maintaining similar cancer control in the form of PSA and testosterone level changes. Conclusion: In conclusion, our study advocates for the reconsideration of bilateral subcapsular orchidectomy as a preferred method for surgical androgen ablation in metastatic prostatic carcinoma, offering comparable efficacy to traditional total orchidectomy approach while prioritizing patient satisfaction and psychological well-being. This suggests a potential paradigm shift in the landscape of cost-effective androgen deprivation therapy within the urological field.

Predicting prostate cancer progression with a Multi-lncRNA expression-based risk score and nomogram integrating ISUP grading

Prostate cancer is a highly heterogeneous disease; therefore, estimating patient prognosis accurately is challenging due to the lack of biomarkers with sufficient specificity and sensitivity. One of the current challenges lies in integrating genomic and transcriptomic data with clinico-pathological features and in incorporating their application in everyday clinical practice. Therefore, we aimed to model a risk score and nomogram containing long non-coding RNA (lncRNA) expression and clinico-pathological data to better predict the probability of prostate cancer progression. We performed bioinformatics analyses to identify lncRNAs differentially expressed across various prostate cancer stages and associated with progression-free survival. This information was further integrated into a prognostic risk score and nomogram containing transcriptomic and clinico-pathological features to estimate the risk of disease progression. We used RNA-seq data from 5 datasets from public repositories (total n = 178) comprising different stages of prostate cancer: pre-treatment primary prostate adenocarcinomas, post-treatment tumors and metastatic castration resistant prostate cancer. We found 30 lncRNAs with consistent differential expression in all comparisons made using two R-based packages. Multivariate progression-free survival analysis including the ISUP group as covariate, revealed that 7/30 lncRNAs were significantly associated with time-to-progression. Next, we combined the expression of these 7 lncRNAs into a multi-lncRNA score and dichotomized the patients into low- or high-score. Patients with a high-score showed a 4-fold risk of disease progression (HR = 4.30, 95 %CI = 2.66–6.97, p = 3.1e-9). Furthermore, we modelled a combined risk-score containing information on the multi-lncRNA score and ISUP group. We found that patients with a high-risk score had nearly 8-fold risk of progression (HR = 7.65, 95 %CI = 4.05–14.44, p = 3.4e-10). Finally, we created and validated a nomogram to help uro-oncologists to better predict patient's risk of progression at 3- and 5-years post-diagnosis. In conclusion, the integration of lncRNA expression data and clinico-pathological features of prostate tumors into predictive models might aid in tailored disease risk assessment and treatment for patients with prostate cancer.

A trinuclear Zn (II) schiff base dicyanamide complex attenuates bacterial biofilm formation by ROS generation and membrane damage and exhibits anticancer activity

A trinuclear Zn (II) complex, [(ZnL{N(CN)2})2Zn], termed complex 1 has been synthesized by the reaction of an aqueous solution of sodium dicyanamide to the methanolic solution of Zn (CH3COO)2, 2H2O and corresponding Schiff base (H2L) which is derived from 1:2 condensation of 1, 4 butane diamine with 3-ethoxy salicylaldehyde. Complex 1 is characterized by elemental analysis, IR, UV and Single X-ray diffraction study. Drug resistance is a growing global public health concern that has prompted researchers to look into advanced alternative treatment modalities. In this context, complex 1 has shown promising antibacterial and antibiofilm efficacy against gram-positive Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus strains. Complex 1 attenuated Staphylococcal biofilm formation by reducing several virulence factors including the formation of extracellular polysaccharide matrix, slime, haemolysin, staphyloxanthin, auto-aggregation, cell surface hydrophobicity, and motility. Notably, complex 1 mechanistically potentiated Reactive Oxygen Species (ROS) generation within the bacterial cells, leading to the damage of bacterial cell membrane followed by DNA leakage and thereby impeding the growth of Staphylococcus aureus. Furthermore, complex 1 significantly exhibited anticancer activity by reducing the growth of prostate adenocarcinoma cells. It obstructed the migration of cancer cells by potentiating apoptosis and arresting the cell cycle at the G2/M phase. In summary, complex 1 could act as a potent candidate for the generation of novel antibacterial, antibiofilm as well as anticancer treatment regimens for the management of drug-resistant biofilm-mediated Staphylococcus aureus infection and lethal prostate malignancy.

The Challenge of Single-Photon Emission Computed Tomography Image Segmentation in the Internal Dosimetry of 177Lu Molecular Therapies.

The aim of this article is to review the single photon emission computed tomography (SPECT) segmentation methods used in patient-specific dosimetry of 177Lu molecular therapy. Notably, 177Lu-labelled radiopharmaceuticals are currently used in molecular therapy of metastatic neuroendocrine tumours (ligands for somatostatin receptors) and metastatic prostate adenocarcinomas (PSMA ligands). The proper segmentation of the organs at risk and tumours in targeted radionuclide therapy is an important part of the optimisation process of internal patient dosimetry in this kind of therapy. Because this is the first step in dosimetry assessments, on which further dose calculations are based, it is important to know the level of uncertainty that is associated with this part of the analysis. However, the robust quantification of SPECT images, which would ensure accurate dosimetry assessments, is very hard to achieve due to the intrinsic features of this device. In this article, papers on this topic were collected and reviewed to weigh up the advantages and disadvantages of the segmentation methods used in clinical practice. Degrading factors of SPECT images were also studied to assess their impact on the quantification of 177Lu therapy images. Our review of the recent literature gives an insight into this important topic. However, based on the PubMed and IEEE databases, only a few papers investigating segmentation methods in 177Lumolecular therapy were found. Although segmentation is an important step in internal dose calculations, this subject has been relatively lightly investigated for SPECT systems. This is mostly due to the inner features of SPECT. What is more, even when studies are conducted, they usually utilise the diagnostic radionuclide 99mTc and not a therapeutic one like 177Lu, which could be of concern regarding SPECT camera performance and its overall outcome on dosimetry.