Biochemical Recurrence Research Articles

Leveraging cell death patterns to predict metastasis in prostate adenocarcinoma and targeting PTGDS for tumor suppression

Metastasis is the major cause of treatment failure in patients with prostate adenocarcinoma (PRAD). Diverse programmed cell death (PCD) patterns play an important role in tumor metastasis and hold promise as predictive indicators for PRAD metastasis. Using the LASSO Cox regression method, we developed PCD score (PCDS) based on differentially expressed genes (DEGs) associated with PCD. Clinical correlation, external validation, functional enrichment analysis, mutation landscape analysis, tumor immune environment analysis, and immunotherapy analysis were conducted. The role of Prostaglandin D2 Synthase (PTGDS) in PRAD was examined through in vitro experiments, single-cell, and Mendelian randomization (MR) analysis. PCDS is elevated in patients with higher Gleason scores, higher T stage, biochemical recurrence (BCR), and higher prostate-specific antigen (PSA) levels. Individuals with higher PCDS are prone to metastasis, metastasis after BCR, BCR, and castration resistance. Moreover, PRAD patients with low PCDS responded positively to immunotherapy. Random forest analysis and Mendelian randomization analysis identified PTGDS as the top gene associated with PRAD metastasis and in vitro experiments revealed that PTGDS was considerably downregulated in PRAD cells against normal prostate cells. Furthermore, the overexpression of PTGDS was found to suppress the migration, invasion, proliferationof DU145 and LNCaP cells. To sum up, PCDS may be a useful biomarker for forecasting the possibility of metastasis, recurrence, castration resistance, and the efficacy of immunotherapy in PRAD patients. Additionally, PTGDS was identified as a viable therapeutic target for the management of PRAD.

Modeling serum M-protein response for early detection of biochemical relapse in myeloma patients treated with bortezomib, lenalidomide and dexamethasone.

Multiple myeloma (MM) treatment guidelines recommend waiting for formal progression criteria (FPC) to be met before proceeding to the next line of therapy. As predicting progression may allow early switching to next-line therapy while the disease burden is relatively low, we evaluated the predictive accuracy of a mathematical model to anticipate relapse 180 days before the FPC is met. A subset of 470/1143 patients from the IA16 dataset who were initially treated with VRd (Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone) in the CoMMpass study (NCT01454297) were randomly split 2:1 into training and testing sets. A model of M-protein dynamics was developed using the training set and used to predict relapse probability in patients in the testing set given their response histories up to 12 or more months of treatment. The predictive accuracy of this model and M-protein "velocity" were assessed via receiver operating characteristics (ROC) analysis. The final model was a two-population tumor growth inhibition model with additive drug effect and transit delay compartments for cell killing. The ROC area under the curve value of relapse prediction 180 days ahead of observed relapse by FPC was 0.828 using at least 360 days of response data, which was superior to the M-protein velocity ROC score of 0.706 under the same conditions. The model can predict future relapse from early M-protein responses and can be used in a future clinical trial to test whether early switching to second-line therapy results in better outcomes in MM.

The accuracy of ultrasensitive PSA in predicting disease progression after radical prostatectomy.

To assess the role of ultrasensitive PSA values (usPSA) after radical prostatectomy in predicting the subsequent biochemical recurrence (BCR). The study included 1836 patients who underwent open or robot-assisted RP at Turku University Hospital between 2003 and 2018. Exclusion criteria involved patients with adjuvant treatments and those who did not reach a PSA nadir <0.1ng/ml, resulting in a final cohort of 1313 patients. The prognostic impact of the optimal usPSA nadir cut-off value 6 months after RP was investigated to predict subsequent BCR for the whole cohort (N = 1313). The optimal usPSA cut-off value was determined for patients at 3-5years post-surgery (N = 806) and beyond 5years (N = 493) of follow-up. We used the area under the curve (AUC) calculation and the Kaplan-Meier method. In a cohort with a median age of 64, primarily featuring Gleason score 7 prostate cancer. uPSA nadir of 0.01 ng/ml (AUC = 0.80) at the first monitoring post-surgery emerged as the optimal cut-off for identifying subjects at low (80%) or high (20%) risk of BCR within the first 3 years. Beyond this period, uPSA values during the first 3 [(AUC = 0.89; 3-5years post-surgery) and (AUC = 0.81; beyond 5years)] and 5 post-surgery years (AUC = 0.85) outperformed uPSA nadir in predicting subsequent BCR. Notably, EAU-defined high-risk patients with low uPSA nadir maintained substantial BCR-free survival. In conclusion, a low usPSA predicts minimal BCR risk over the next 2-3years post-measurement. Patients with low usPSA can benefit from reduced post-surgery PSA monitoring at 2- to 3-year intervals without compromising outcomes. This strategic approach optimizes resource allocation in busy urological outpatient clinics, especially valuable in publicly reimbursed healthcare systems like Finland.

Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis.

Recent advancements in the management of biochemical recurrence (BCR) following local treatment for prostate cancer (PCa), including the use of androgen receptor signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options. We aimed to compare salvage therapies in patients with BCR after definitive local treatment for clinically non-metastatic PCa with curative intent. In October 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) and prospective studies reporting data on the efficacy of salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). We included 19 studies (n = 9117); six trials analyzed RT-based strategies following RP, ten trials analyzed hormone-based strategies following RP ± RT or RT alone, and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p < 0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies, the addition of elective nodal RT and androgen deprivation therapy (ADT) was found to be the most effective in terms of MFS. On the other hand, among hormone-based strategies, enzalutamide + ADT showed the greatest benefit for both MFS and OS. The combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred treatment for eligible patients with post-RP BCR based on our analysis. In remaining patients, or in case of post-RT recurrence, especially for those with high-risk BCR, the combination of ADT and ARSI should be considered.

Prediction of biochemical recurrence after radical prostatectomy from primary tumour characteristics.

To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour. Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria. Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed. Tumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer

BackgroundEvidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT).MethodsPCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis.ResultsTOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients.ConclusionsIn this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

Oncologic and functional outcomes following robot assisted radical prostatectomy: 15-Year experience in a Latin American referral center

BackgroundProstate cancer is the most common cancer in men with more than 52,000 cases diagnosed every year on average. With the introduction of robotic surgery, robotic assisted radical prostatectomy (RARP) has become a popular treatment option in recent years. Achieving oncological control, urinary continence and satisfactory erectile sexual function after RP is the main goal also known as “trifecta”. All these outcomes are highly influenced by surgical experience and caseload. The main objective of this study is to analyze oncological and functional outcomes in RARP after 15 years of experience. MethodsFrom 2008 until December 2023, 1790 RARP for localized prostate cancer were performed. A retrospective analysis was conducted based on prospectively collected data correlated with electronic medical records. ResultsSubgroup analyses were conducted in order to evaluate oncological and functional outcomes (n: 1400). Red blood cell transfusion and conversion to open surgery rate was 1.9 % and 0.1 %, respectively. Mean surgical time was 194 min. Mean follow-up time was 69.5 months, 23.8 % patients experienced biochemical recurrence and 1 % died, primarily due to disease progression. Estimated 10-year recurrence-free survival was 68.7 % (95 % CI 67.2–72.2) while estimated 10-year overall survival was 97.9 % (95 % CI 96.3–99.4). Overall urinary continence rate at 2 years was 86.9 % while satisfactory erectile function rate at 18 months was 56.8 %. ConclusionsRobotic-assisted radical prostatectomy has become a standard surgical technique in our urological practice for the management of clinically localized and locally advanced prostate tumors in selected cases. After 15 years since the inception of our robotic surgery program, we can conclude that our results are comparable to those published in the international literature, enabling patients to maintain satisfactory sexual function with a high continence rate within the first year of surgery.

Imaging assessment of prostate cancer recurrence: advances in detection of local and systemic relapse.

Prostate cancer (PCa) relapse, defined either by persistent PSA levels (after RP) or biochemical recurrence (BCR), is a common occurrence. The imaging evaluation of patients experiencing PCa relapse has undergone significant advancements in the past decade, notably with the introduction of new Positron Emission Tomography (PET) tracers such as Prostate-specific membrane antigen (PSMA), and the progress in functional Magnetic Resonance Imaging (MRI). This article will explore the role of traditional imaging, the evolution of MRI towards the development of the Prostate Magnetic Resonance Imaging for Local Recurrence Reporting (PI-RR) scoring system, and how next-generation imaging is enhancing diagnostic accuracy in the setting of PCa relapse, which is essential for adopting personalized strategies that may ultimately impact outcomes.

Dose compliance of estramustine phosphate in neoadjuvant chemohormonal therapy combined with degarelix acetate predicts the biochemical recurrence in patients with very high-risk prostate cancer who underwent robot-assisted radical prostatectomy.

The objective of this study is to evaluate the safety and efficacy of neoadjuvant degarelix acetate and low-dose estramustine phosphate for high-/very high-risk prostate cancer. Overall, 187 patients diagnosed with National Comprehensive Cancer Network high-/very high-risk cTanyN0M0 localized prostate cancer who consented to undergo robot-assisted radical prostatectomy after receiving neoadjuvant chemohormonal therapy for 6 months were prospectively enrolled between December 2017 and March 2023. Adverse events, perioperative and histopathological outcomes, and biochemical recurrence-free survival rates were examined. Survival analysis compared the estramustine phosphate completion and reduction groups. Thirty-six patients discontinued neoadjuvant therapy in <5 months owing to adverse events (n = 34) or other reasons (n = 2). Eleven were excluded for being in the postoperative castration range. Of the 140 patients who underwent surgery, 124 continued with two tablets of estramustine phosphate and 16 with one tablet. Overall, 82 patients were very high-risk. Histopathological outcomes were significantly worse in the very high-risk group than those in the high-risk group. Very high-risk status and estramustine phosphate reduction were significant factors in biochemical recurrence in multivariate analysis. The biochemical recurrence-free survival rate in very high-risk patients was significantly lower in the estramustine phosphate dose reduction group than in the completion group but not significant in high-risk patients. Major adverse events were anemia (n = 174), elevated transaminase levels (n = 68), and deep vein thrombosis (n = 24). Severe adverse events included acute coronary syndrome (n = 4) and pulmonary embolism (n = 3). Dose compliance with estramustine phosphate predicted biochemical recurrence in patients with very high-risk prostate cancer undergoing robot-assisted radical prostatectomy with neoadjuvant chemohormonal therapy.

Long-term oncological outcomes after radical prostatectomy in a non-university teaching hospital

The evaluation of oncological outcomes after radical prostatectomy (RP) is a major component of quality control in prostate cancer (PCa) centres. To evaluate the oncological outcomes after RP in a non-university teaching hospital and compare them with other high-volume PCa centres. This study included 1,161 patients after RP who were divided into two risk groups. Low-risk: localised PCa (pT2) and prostate-specific antigen (PSA)≤ 20 ng/ml, Gleason score (GS) 6-7b and pN0. High-risk: locally advanced PCa (≥pT3a) and/or PSA >20 ng/ml and/or GS≥ 8 and/or pN1. Risk groups and clinicopathological features were correlated to biochemical recurrence (BCR)-free survival, cancer-specific survival (CSS) und overall survival (OS). The 10-year BCR-free survival, CSS und OS were 68.4%, 47.0% and 100% in the low-risk group and 87.4%, 89.0% and 73.9% in the high-risk group, respectively; the outcomes between risk groups were statistically significant (p<0.05). A multivariate Cox regression analysis was performed. GS was the most significant prognostic factor for CSS (p=0.00001) und BCR-free survival (p=0.00036). Nodal involvement (pN1) was strongly associated with CSS (p=0.00004). Age was the most important factor for overall survival in the high-risk group (p=0.0011). RP could be a curative treatment option for advanced PCa in selected cases. GS is the most important prognostic factor. Good oncological outcomes can also be achieved in non-university teaching hospitals.

Local extension findings on MRI compensate for the ability of pathological staging to predict oncological outcome.

We investigated whether local extension findings on preoperative MRI and excisional pathology are associated with positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy. We identified 704 of our patients that underwent robot-assisted radical prostatectomy between 2012 and 2020, and extracted the 326 patients who had preoperative MRI scans and a radiologist reading. These patients were classified into groups according to the presence of local extension on MRI and pathological findings: ≤ cT2pT2 (195 cases), ≤ cT2pT3 (55 cases), cT3pT2 (31 cases), and cT3pT3 (45 cases). We compared positive surgical margin and biochemical recurrence between them. Median age was 69years, positive surgical margin rate was 20.2%, and five-year biochemical recurrence rate was 20.3%. Of the 226 patients without local invasion on excisional pathology, those with local extension on MRI (cT3pT2) had relatively higher positive surgical margin rate (29.0% vs. 14.4%, p = 0.05) and significantly higher five-year biochemical recurrence rate (25.8% vs. 9.3%, p = 0.01) than those without local extension on MRI (≤ cT2pT2). Similarly, among the 100 patients with local extension on excisional pathology, those with cT3pT3 had relatively higher positive surgical margin (37.8% vs. 21.8%, p = 0.08) and significantly higher five-year biochemical recurrence (53.3% vs. 29.3%, p = 0.01) than those with ≤ cT2pT3. In multivariate analysis, local extension on MRI was an independent predictor of biochemical recurrence (OR 2.1, 95%CI 1.1-3.9, p = 0.01). Local extension on MRI is a prognostic factor independent of pathological stage. The use of MRI may complement the prognostic value of excisional pathology of prostate cancer.

[18F]AlF-PSMA-11 PET in diagnosing prostate cancer: a head-to-head comparison with [68Ga]Ga-PSMA-11 PET and an exploration of dual-phase scanning

PurposeTo evaluate the physiological distribution and tumour detection ability of [18F]AlF-PSMA-11 positron emission tomography (PET) dual-phase scans in patients with prostate cancer (PCa).MethodsAs a retrospective study, clinical and PET data of PCa patients who underwent dual-phase [18F]AlF-PSMA-11 PET of routine scan (45–50 min) and delayed scan (120 min) from November 2020 to June 2021 were collected, and physiological and pathological regions of interest were quantified to determine the time-dependent maximum standardized uptake value (SUVmax) of [18F]AlF-PSMA-11. Part of the above subjects who underwent [68Ga]Ga-PSMA-11 PET in the following 6 months were included in a head-to-head comparison. The difference with a p-value < 0.05 was defined as statistical significance. Diagnosis accuracy of primary and metastatic lesions was measured referring to the surgical findings, pathology, and follow-up imaging.Results[68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 were of the comparable uptake in glands in head, but the latter was of a significant lower distribution in liver and spleen. For the 25 patients initially diagnosed with prostate cancer and 3 patients with biochemical recurrence after radical surgery, the SUVmax of the primary lesions, lacrimal glands, parotid glands and submandibular glands was higher at 120 min compared to that at 45–50 min, but not a significant difference. SUVmax of the liver, spleen and bladder decreased significantly at 120 min, but the bladder SUVmax remained higher than that of primary lesions. SUVmax of the kidneys and centrum was the same in dual-phase scans. For the 31 primary lesions detected in [18F]AlF-PSMA-11 PET, both the SUVmax of the two phases kept the positive correlation with PSA, Gleason score and initial risk stratification. For the 39 distant metastatic lesions, 94.87% accuracy of routine scan and 100% accuracy of delayed scan were acquired, and 7.14% patients (2/28) benefited from the dual-phase [18F]AlF-PSMA-11 scans that revealed novel information on metastatic lesions compared to the routine scan.Conclusion[18F]AlF-PSMA-11 PET expanded the time window and further decreased metabolic background of [68Ga]Ga-PSMA-11 PET. The dual-phase scan of [18F]AlF-PSMA-11 PET can benefit prostate cancer diagnosis via providing more PSMA-specific information.

The added value of 68Ga-PSMA PET/CT in anatomical staging of prostatic carcinoma in correlation with the histopathological zonal staging

BackgroundProstate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging.ResultsZonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings.Conclusions68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels.

MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan–Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03–3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Impact of Perioperative Lidocaine on Neutrophil Extracellular Trapping and Serum Cytokines in Robot-Assisted Radical Prostatectomy: Randomized Controlled Study.

Background and Objective: This randomized controlled trial investigated the influence of perioperative lidocaine administration on the postoperative inflammatory response in patients undergoing robot-assisted radical prostatectomy, with the results having potential implications for postoperative recovery and cancer recurrence via neutrophil extracellular trapping (NETosis). Materials and Methods: In total, 58 patients with localized prostate cancer were randomly assigned to receive an intravenous infusion of 2% lidocaine or a saline placebo intraoperatively. Serum levels of interleukin (IL)-6, IL-10, and IL-17, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, neutrophil elastase (NE), citrullinated histone3 (CitH3), and myeloperoxidase (MPO) were determined preoperatively and at 24 h postoperatively. Biochemical recurrence (BCR) was assessed over a follow-up period of 2 years. Results: The lidocaine group showed a significant change in MPO, a greater reduction in IL-10 level, and a smaller increase in the NE level compared to the placebo group, suggesting a modulatory effect of lidocaine on certain anti-inflammatory and neuroendocrine pathways. No significant difference in the BCR rate was observed between the two groups. Conclusions: Perioperative lidocaine administration selectively modulates certain inflammatory and neuroendocrine responses after robot-assisted radical prostatectomy surgery, potentially influencing recovery outcomes. These findings highlight the need for further investigations of the role of lidocaine in Enhanced Recovery After Surgery protocols, particularly in oncologic surgeries.

Construction of a cuproptosis‑related lncRNA signature to predict biochemical recurrence of prostate cancer.

Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making.

TREATMENT OF PROSTATE CANCER USING ROBOT-ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY WITH RECONSTRUCTION OF THE PROXIMAL PROSTATIC URETHRA

Introduction: Prostate cancer (PCa) has been one of the leading oncologic pathologies for decades. In the low-risk group the nerve-sparing technique of surgery is used, which is supplemented by preservation and reconstruction of the prostatic urethra. The effectiveness of this technique in preserving the quality of urination, a significant reduction in the rehabilitation time of patients without reducing the quality of the oncologic result of the operation is described. The aim of the study: To evaluate the long-term results of robot-assisted laparoscopic radical prostatectomy with prostatic urethra reconstruction. Materials and Methods: 60 patients were included in the study. Patients’ selection criteria: low risk of disease prevalence, focal form, tumor location more than 4 mm from the prostatic urethra. During the operation a precision dissection of the prostatic urethra from the prostate is performed. Up to 2cm of the proximal section is preserved, a similar manipulation is performed with the distal urethra. After removal of the prostate, the integrity of the urethra is restored by applying urethro-urethral anastomosis. Before the operation the patients underwent standard examination, including general clinical tests, blood test for prostate-specific antigen (PSA), ultrasound, magnetic resonance imaging (MRI) with 3D modeling. There are also results of pathohistological report, International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Quality of Life due to urinary disorders, Partin nomogram. Results: All studied parameters showed good results after 1 month, which were maintained after 6 and 12 months. In 1 patient (1.67%) there was a biochemical recurrence after 6 months (PSA 0.35 ng/ml), which was visualized by MRI as an area of contrast accumulation in the area of neurovascular bundles, the preserved urethra was intact. Conclusion: Based on the results of the study, there is preservation of the quality of life and no increase in oncologic risk one year after surgery. It is possible to expand the selection criteria and perform prostatic urethra preservation without performing nerve-sparing.

Trifecta Outcomes After Use of 3-Dimensional Digital Models for Planning of Robotic Prostatectomy

Planning complex operations such as robotic-assisted laparoscopic radical prostatectomy (RALP) requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) scans to understand 3-dimensional (3D) patient anatomy. Three-dimensional digital models for planning RALP may allow better understanding of patient anatomy and may lead to better patient outcomes, although data are currently limited. To determine surgical outcomes after RALP when surgeons reviewed 3D digital models during operative planning. This study was a planned secondary analysis of a multicenter, single-blind, randomized clinical trial conducted at 6 large teaching hospitals in the US. The study was conducted between January 1, 2019, and December 31, 2022, and included patients undergoing RALP. Patients were assessed and recruited at the time of surgical consultation. Final data analysis was conducted between August and December 2023. Patients were randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and multiparametric MRI only or to an intervention group in which imaging and biopsy results were supplemented with a 3D digital model. This model was viewed on the surgeon's mobile phone in 3D format and picture-in-picture on the robotic console screen. The primary outcome measure for the overall study was oncologic outcomes after RALP, measured as prostate-specific antigen (PSA) detectability. Secondary outcomes were sexual function and urinary function, measured with Sexual Health Inventory for Men (SHIM) scores and rates of urinary incontinence, respectively, as well as use of salvage or adjuvant radiation therapy (RT) or androgen deprivation therapy (ADT). Trifecta outcomes were defined as undetectable PSA without RT or ADT, SHIM score categorically the same or greater than preoperatively, and complete continence. Univariate analysis was performed to compare outcomes between groups. This trial included 92 patients undergoing RALP (51 in the control group and 41 in the intervention group). Their mean (SD) age was 62 (7.4) years; 10 patients (10.9%) were Black and 67 (72.8%) were White. At 18 months postsurgery, the intervention group had lower rates of biochemical recurrence (PSA level >0.1 ng/mL, 0 vs 7 [17.9%]; absolute difference, 17.9% [95% CI, 1.8% to 31.8%]; P = .01) and were significantly less likely to undergo adjuvant or salvage RT (1 [3.1%] vs 12 [31.6%]; absolute difference, 28.5% [95% CI, 10.1% to 46.7%]; P = .002) compared with the control group. Sexual function at 18 months postsurgery was significantly better in the intervention group (mean [SD] SHIM score, 16.8 [8.7] vs 9.8 [7.7]; absolute difference, 7.0 [95% CI, 2.6 to 11.4]; P = .002) and urinary function was unchanged (total continence, 22 [78.6%] vs 29 [80.6%]; absolute difference, 2.0% [95% CI, -17.9% to 21.9%]; P = .84) compared with the control group. Trifecta outcomes were achieved for 12 (48.0%) patients in the intervention group and 3 patients (10.0%) in the control group (absolute difference, 38.0% [95% CI, 14.4% to 61.6%]; P = .002). In this secondary analysis of a randomized clinical trial, patients whose surgical planning of RALP involved 3D digital models had better oncologic and functional outcomes. Further work should assess the effect of 3D models in a broader set of patients, physicians, and hospital settings. ClinicalTrials.gov Identifier: NCT03943368.

Local salvage therapies in patients with radio-recurrent prostate cancer following external beam radiotherapy: a systematic review and meta-analysis.

To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT). We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI). Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively. In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made.