Underwent Radical Prostatectomy Research Articles

Effects of preoperative and postoperative carbohydrate loading on gastrointestinal function and stress-induced inflammation after radical prostatectomy

Background: Early postoperative oral clear liquid diet has been shown to enhance postoperative recovery. However, the standard strategy for this diet has not been established. The authors’ aim was to investigate the combined effect of preoperative and early postoperative carbohydrate loading on postoperative stress and gastrointestinal function of patients by standardizing the starting time, type, volume, and concentration of carbohydrate drinks. Materials and methods: Fifty-three patients undergoing radical prostatectomy were randomly assigned to two groups. Both groups received a carbohydrate loading of 400 ml (12.5%) overnight and 2 h before surgery. The intervention group (n=29) started a 400 ml (12.5%) carbohydrate loading 6 h after surgery and consumed it within 24 h, while the control group (n=32) drank water. The primary outcomes–postoperative fasting blood glucose, fasting insulin, C-reactive protein (CRP), interleukin-6 levels, and gastrointestinal function–were recorded. Secondary outcomes included subjective comfort assessment, the first postoperative intake of semi-fluid food time, and drainage volume. Results: Compared with the control group, the intervention group had lower CRP levels on postoperative day 1 (POD1)/POD2 and less drainage volume on POD1. The intervention group also experienced shorter times to the first postoperative flatus and the first consumption of semi-fluid foods; their 72-h postoperative protein intake was higher than that of the control group. Conclusion: The results suggest that combined preoperative and postoperative carbohydrate loading can alleviate stress-induced inflammation and promote the recovery of postoperative gastrointestinal function.

Prostate Volume is A Predictor of Gleason Score Upgrading after Radical Prostatectomy in Low-Risk Prostate Cancer: A Systematic Review and Meta-analysis.

The prediction of Gleason score (GS) upgrading in patients diagnosed with low-risk prostate cancer is particularly important when opting for active surveillance (AS). Thus, we aimed to explore the association between prostate volume and GS upgrading after radical prostatectomy in low-risk prostate cancer through a meta-analysis. Multiple databases (Web of Science, MEDLINE, Embase, Scopus, and the Cochrane Library) were searched for eligible studies regarding this issue and reporting sufficient data up to May 2023. Specific search terms such as prostate cancer, radical prostatectomy, and prostate volume were used in our search strategy. Multivariable-adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Twenty studies comprising 14,823 patients who underwent radical prostatectomy matched our eligibility criteria. Moreover, GS upgrading between biopsy and surgical pathological specimens occurs in 32.2% (4,771) of cases. The results showed that smaller prostate volume is significantly associated with GS upgrading in patients with low-risk prostate cancer (OR = 1.08, 95% CI = 1.05-1.11; P < 0.001; I-square [I2] = 89.8%) from biopsy to radical prostatectomy after adjusting for confounding factors. Moreover, the results of our subgroup analyses revealed that smaller prostate volume remained a substantial risk factor of GS upgrading in the studies designed as retrospective cohorts and case-control studies performed in America, Italy, Turkey, and China. The findings are robust as indicated by sensitivity and meta-regression analyses. Smaller prostate volume predicts clinically substantial GS upgrading in patients diagnosed with lowrisk prostate cancer after radical prostatectomy. The intriguing findings might be helpful when management options other than surgery are selected based on the inability to recognise the true pathological GS of patients for AS. Further studies focus on risk-stratification and treatment planning for patients with low-grade prostate cancer are still needed to verify our results.

EAU RISK GROUPS APPLIED ON PATIENTS TREATED WITH RADICAL PROSTATECTOMY - ANALYSIS OF PATHOLOGY SPECIMENS AND PATIENT SURVIVAL

Purpose: The European Association of Urology (EAU) classifies patients with prostate cancer into three risk groups - low-risk, intermediate- and high-risk depending on the probability of biochemical progression after treatment with curative intent (either radical prostatectomy or radiotherapy). The aim of the present study is to analyze our experience with patients who underwent radical prostatectomy and to look for the relationship between the pathological results from the operation and the distribution of patients into risk groups. Material/Methods: A single-center, non-interventional study was conducted. The study was performed after analysis of patients undergoing radical prostatectomy (either open or laparoscopic) at the Clinic of Urology in St. Anna Hospital in Varna. The number of patients available for analysis was 201. Data were analyzed with IBM SPSS version 23. Results: We found that high-risk patients had unfavorable results from the examination of the pathology specimens- patients with pT3a and pT3b were more often from the high-risk group. High-risk patients were also at increased risk of PSA progression and development of distant metastases. Conclusions: The EAU-risk groups will probably undergo changes connected with the improved methods for the diagnosis of prostate cancer. But still, it is a valid tool which correctly predicts the unfavorable pathology of the removed specimen and also the risk of biochemical progression after radical prostatectomy.

Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer-Lateralization Concept.

Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

The association between pre‐diagnostic levels of psychological distress and adverse effects after radical prostatectomy

AbstractObjectivesTo prospectively analyse the associations between pre‐diagnostic levels of anxiety and depression and patient‐reported urinary and sexual adverse effects after radical prostatectomy in a population‐based setting.Patients and MethodsIn three Norwegian county hospitals, men referred with a suspicion of prostate cancer were asked to fill out a patient‐reported outcome measurement (PROM) questionnaire prior to prostate biopsy. Those who later underwent radical prostatectomy were stratified into three distress groups according to their Hopkins Symptom Checklist 5‐score. Additional PROM questionnaires, including the EPIC‐26 to measure adverse effects, were collected at 6 and 12 months postoperatively. Multivariable mixed models were estimated and post hoc pairwise comparisons performed to explore differences in adverse effects between distress groups.ResultsA total of 416 men were included at baseline and of those, 365 (88%) returned questionnaires at 6 months and 360 (87%) at 12 months. After adjusting for confounders, men with high distress at baseline had worse urinary incontinence domain score (58.9 vs. 66.8, p = 0.028), more urinary bother (64.7 vs. 73.6, p = 0.04) and a higher risk of using incontinence pads (70.6% vs. 54.2%, p = 0.034) at 6 months than those with low distress. There was no difference in the sexual domain scores between distress groups postoperatively, but the high‐distress group expressed more sexual bother (24.9 vs. 37.5, p = 0.015) and the intermediate‐distress group had a greater probability of using sexual medications or devices (63.8% vs. 50.0%, p = 0.015) than the low‐distress group at 6 months. At 12 months scores generally improved slightly and differences between distress groups were less evident.ConclusionMen with higher levels of anxiety and depression before prostate biopsy report more urinary and sexual adverse effects after radical prostatectomy. This should be considered both in treatment decision‐making and during follow‐up after radical prostatectomy.

Analysis of biopsy pathology and risk factors of lymph node metastasis in prostate cancer.

To explore the relationship between biopsy pathology and lymph node metastasis in patients with prostate cancer (PCa), and to identify risk factors of lymph node metastasis (LNM). Patients diagnosed with prostate cancer were respective screened between Jan 2015 and May 2022. Patients diagnosed PCa via 13-core ultrasound-guided biopsies and underwent radical prostatectomy and lymph node dissection were identified. The clinicopathological characteristics of the patients were recorded. Relationships between LNM and non-LNM were analyzed using chi-square and independent samples t-test. Logistic regression model was fitted to analyze the risk factors of lymph node metastases. Two hundreds and fifteen patients were included, sixty-seven patients had lymph node metastasis. Gleason scores in LNM group were higher than that in non-LNM group (8.5 ± 0.9 VS 7.5 ± 1.5, p < 0.001), positive biopsy in non-LNM group was significantly lower than that in LNM group (p < 0.001), Binary logistic regression analysis indicated number of positive biopsy and number of removed lymph nodes increased the risks of LNM (odds ratio, OR = 1.28, 95% confidence interval, CI = 1.16-1.42, p < 0.001; OR = 1.11, 95% CI = 1.06-1.17, p < 0.001; respectively). Number of positive biopsy in internal gland but not external gland was significant associated with LNM (OR = 1.66, 95% CI = 1.34-2.06, p < 0.001; OR = 1.19, 95% CI = 0.88-1.61, p = 0.262; respectively). The patients with lymph nodes dissection more than 13 were about four times more likely to detect lymph node metastasis than those fewer than 13 (OR = 3.92, 95% CI = 2.10-7.33, p < 0.001). The risk of lymph node metastasis increased with the number of positive prostate biopsy cores, and tumors in the internal gland were more likely to cause lymph node metastasis. In addition, lymph node metastasis was more likely to be found when the number of lymph nodes dissection was greater than 13.

99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of 227 consecutive patients with newly diagnosed prostate cancer: a 5-year monocentric retrospective study.

The purpose of this study was to assess the effectiveness of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of patients with newly diagnosed PCa. A retrospective analysis was conducted on 227 consecutive patients who underwent [99mTc]Tc-HYNIC-ALUG SPECT/CT imaging for the primary staging of newly diagnosed PCa. The presence and location of PSMA-positive lesions were determined, and the maximum standardized uptake values (SUVmax) of the primary prostate tumor were also measured. The metastatic findings and SUVmax were stratified according to International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) levels, and D'Amico classification. Furthermore, the [99mTc]Tc-HYNIC-ALUG SPECT/CT findings were compared to the histopathological findings in patients who had undergone radical prostatectomy with pelvic lymph node dissection (PLND). Of the 227 patients, 92.1% (209/227) had positive [99mTc]Tc-HYNIC-ALUG SPECT/CT findings. Advanced disease was detected in 38.8% (88/227) of the patients and was positively correlated with increasing ISUP grade and PSA levels. Lymph node metastases (both pelvic and extrapelvic), bone metastases, and visceral metastases were detected in 30.0% (68/227), 25.6% (58/227), and 3.1% (7/227) of the patients, respectively. For the 129 patients who underwent radical prostatectomy with PLND, the sensitivity of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the evaluation of PCa was 90.7% (117/129). The sensitivity, specificity, accuracy, and positive and negative predictive values for detecting pelvic lymph node metastases on [99mTc]Tc-HYNIC-ALUG SPECT/CT were 23.5% (12/51), 93.6% (73/78), 65.9% (85/129), 70.6% (12/17), and 65.2% (73/112), respectively. Among the 209 patients with PSMA-avid primary prostate disease, the SUVmax of the primary prostate tumor was significantly associated with ISUP grade (p<0.0001), PSA levels (p<0.0001), D'Amico classification (p<0.0001), and advanced disease (p<0.0001). Receiver operating characteristic (ROC) analysis revealed that a PSA level >19.8 ng/ml and SUVmax of the primary prostate tumor >7.4 had a sensitivity of 71.6% and 71.6% and specificity of 76.9% and 82.6%, respectively, for detecting metastatic disease. [99mTc]Tc-HYNIC-ALUG SPECT/CT emerges as a valuable imaging tool for the initial staging of newly diagnosed PCa. The presence of advanced disease and the SUVmax of the primary prostate tumor were positively correlated with ISUP grade and PSA levels.

Ductal prostate cancer staging: Role of PSMA PET/CT.

To evaluate the accuracy of PSMA PET/CT in the diagnosis and clinical staging of prostatic ductal adenocarcinoma (DAC). Two Caucasian men 58 and 62 years old were admitted to our Department for dysuria: the patients had not familiarity for prostate cancer (PCa), PSA values were 5.6 and 2.8 ng/ml, digital rectal examination was positive, multiparametric magnetic resonance image (mpMRI) showed for both the presence of an index lesion PIRADS score 5. The patients underwent extended transperineal prostate biopsy combined with four mpMRI/TRUS fusion biopsy under sedation and antibiotic prophylaxis; biopsy histology demonstrated the presence of a mixed PCa characterized by DAC and acinar PCa (Grade Group 4/Gleason score 8). The patients underwent clinical staging performing lung and abdominal CT, bone scan and fluoride 18 (18F) PSMA PET/CT. Conventional imaging was negative for distant metastases; 18F-PSMA PET/CT showed in both patients an intraprostatic lesion characterized by a standardized uptake value (SUVmax) equal to 4.6 and 4.9 in the absence of distant lesions suspicious for metastases. Following multidisciplinary evaluation, the patients underwent radical prostatectomy plus extended pelvic lymphadenectomy. Definitive specimen showed the presence in both cases of a mixed pT3bN1 PCa (ductal plus acinar pattern Grade Group 4) with positive surgical margins, neuronal invasion, and nodes metastases (5/20 and 6/24, respectively). Post-operative PSA in the two patients was 0.8 and 0.3 ng/ml, therefore patients underwent adjuvant therapy. Conventional imaging and PSMA PET/CT could result inadequate in clinical staging of DAC, the use of more imaging data (i.e. mpMRI and/or F-18 FDG) could improve overall accuracy.

Plant-based diet associated with better quality of life in prostate cancer survivors.

Plant-based diets have many health benefits, including a lower risk of fatal prostate cancer, and greater environmental sustainability. However, less is known regarding the impact of plant-based diets on quality of life among individuals diagnosed with prostate cancer. The authors' objective was to examine the relationship between plant-based diet indices postdiagnosis with quality of life. This prospective cohort study included 3505 participants in the Health Professionals Follow-Up Study (1986-2016) with nonmetastatic prostate cancer. Food-frequency questionnaires were used to calculate overall and healthful plant-based diet indices. Quality-of-life scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations over time between plant-based diet indices and quality-of-life domains (sexual functioning, urinary irritation/obstruction, urinary incontinence, bowel functioning, hormonal/vitality), adjusted for demographics, oncologic history, body mass index, caloric intake, health-related behaviors, and comorbidities. The median age at prostate cancer diagnosis was 68years; 48% of patients underwent radical prostatectomy, and 35% received radiation as primary therapy. The median time from diagnosis/treatment to first the quality-of-life questionnaire was 7.0years. A higher plant-based diet index was associated with better scores for sexual function, urinary irritation/obstruction, urinary incontinence, and hormonal/vitality. Consuming more healthful plant-based foods was also associated with better sexual and bowel function, as well as urinary incontinence andhormonal/vitality scores in the age-adjusted analysis, but not in the multivariable analysis. This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with modestly higher scores in quality-of-life domains among patients with prostate cancer.

Patient-centred pathology reporting improves patient experience and understanding of disease in prostate cancer care.

Patient-centred (PC) and holistic care improves patient satisfaction and health outcomes. We sought to investigate the benefit of utilising a PC pathology report in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa). Our study aimed to evaluate and compare patient understanding of their PCa diagnosis after RP, upon receiving either a standard histopathology report or a personalised and PC report (PCR). Moreover, we evaluated knowledge retention at 4 weeks after the initial consultation. We invited patients undergoing RP at three metropolitan Urology clinics to participate in our randomised controlled study. Patients were randomised to receive either a PCR or standard pathology report. Patient satisfaction questionnaires (Perceived Efficacy in Patient-Physician Interactions [PEPPI], Consultation and Relational Empathy [CARE] and Communication Assessment Tool [CAT]) and a knowledge test were conducted within 72 h of the initial appointment and again at 4 weeks. Accurate recollection of Gleason grade group (GGG) and extracapsular extension (ECE) were classified as 'correct'. Baseline demographic data included age, education, marital and employment status, pre-op prostate specific antigen (PSA) and clinical stage. Baseline data were tested for differences between groups using the Student's t test, chi-squared test or Fisher's exact test depending on whether data were continuous, categorical or sparse. Comparison of correctly answered 'knowledge' questions was analysed using chi-squared test. A significance level of p ≤ 0.05 was used. Data from 62 patients were analysed (30 standard vs. 32 PCR). No significant differences in baseline demographics were found between groups. Both groups reported high levels of satisfaction with their healthcare experiences in all domains of patient-physician rapport, empathy and communication. There were no significant differences between groups in PEPPI (p = 0.68), CAT (p = 0.39) and CARE (p = 0.66) scores, at baseline and 4 weeks. Ninety-three per cent of patients who received the PCR understood the report while 90% felt the report added to their understanding of their PCa. Regarding patient knowledge, the PCR group had significantly more correct answers on GGG and ECE as compared with the standard report group at baseline and 4 weeks (p < 0.001 and 0.001, respectively). Our findings demonstrate that PC pathology reports improve patient knowledge and understanding of their PCa that is retained for at least 4 weeks after initial receipt of results.

(283) Evaluating The Impact of Prior Prostate Cancer Hormonal Therapy on Satisfaction Rates in Post Implantation of Inflatable Penile Prosthesis

Abstract Introduction Androgen deprivation therapy (ADT), a vital treatment modality for prostate cancer, effectively reduces androgens (testosterone &amp; dihydrotestosterone) through inhibiting its production or blocking its action, thereby impeding the growth and even causing shrinkage of prostate cancer cells. It has been utilized in the treatment of early-stage, recurrent, and metastatic cases of prostate cancer. Common side effects were hot flashes, fatigue, decreased bone density, mood changes, decrease libido and sexual dysfunction. Inflatable penile prosthesis (IPP) implantation has already emerged as a highly successful treatment option, garnering significant satisfaction rates among the general population with erectile dysfunction (ED) and specifically in prostate cancer patients who underwent radical prostatectomy (RP) or radiation therapy (XRT). Nevertheless, there remains a dearth of literature examining satisfaction rates specifically in patients with hormonal therapy history post-IPP implantation Objective Our study aims to comprehensively evaluate patient satisfaction rates post IPP implantation for ED, in relation to their ADT status for prostate cancer. Methods A retrospective chart review from our institutional database was conducted to identify 529 patients who underwent IPP at our institution by a single surgeon from 2017 to 2022. Eligible patients for inclusion included those with histological confirmation of prostate cancer treated by RP or XRT with or without hormonal therapy, followed by IPP implantation for ED, and had completed the 11-item Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) validated questionnaire with data available for review. All EDITS questionnaires were administered at least 6 months from operative date or later. Eligible patients were screened for placement into one of two groups depending on their ADT status. To prevent crossover confounding; patients with history of other types of hormonal therapy for non prostate cancer patients were excluded. Results A total of 96 patients were included and categorized into group 1 (ADT, n=30) and group 2 (No ADT, n=66). All patients' demographics were summarised in Table 1. The study revealed notable results regarding the impact of ADT on post IPP satisfaction rates which exhibited a significantly lower EDITS score compared to group 2 (P= 0.034) (Figure 1). Furthermore, group 1 showed no significant changes in post IPP satisfaction with relation to type of prostate cancer treatment offered. While group 2 demonstrated a significantly higher EDITS score post IPP in RP patients compared to XRT, which aligns with the reported literature. Conclusions Our initial findings suggest that despite IPP implantation for managing erectile dysfunction, which is expected to yield high satisfaction rates compared to other available treatment options, Yet the previous or ongoing history of androgen deprivation therapy continues to influence such patients' satisfaction. These observations provide valuable insights; however, further investigation on a larger scale is essential to validate these trends. Additionally, it is crucial to offer proper counseling to these patients regarding the expected outcomes to assist them in making informed decisions regarding the management of their ED. Lastly, the routine use of validated questionnaires has demonstrated significant value in quantifying device and sexual satisfaction following IPP implantation and should be considered as an integral evaluation tool. Disclosure No.

Evaluation of AR, AR-V7, and p160 family as biomarkers for prostate cancer: insights into the clinical significance and disease progression

PurposeTo assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression.MethodsThe study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints.ResultsThe AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001).ConclusionUpregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.

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.

PSMA PET/CT and mpMRI discrepancies in prostate cancer detection with whole-mount histopathology gold standard.

284 Background: Multiparametric MRI (mpMRI) and PSMA-PET are complementary imaging modalities used in the pre-surgical evaluation of patients with prostate cancer (PCa). The aim of this study was to evaluate the imaging and pathology parameters associated with PSMA-PET and mpMRI disagreement with each other and with gold standard histopathology. Methods: Patients undergoing radical prostatectomy (RP) with pre-surgical PSMA-PET and mpMRI were screened for inclusion in this retrospective analysis. Patients had the imaging scans done &lt;3 months from each other, and whole mount histopathology (WMHP) slides available. Two nuclear medicine physicians and 2 radiologists independently contoured PCa lesions on PSMA-PET and mpMRI, respectively. A consensus read was done with a third reader for each modality, and a majority rule was applied (2:1). Quantitative measures were extracted on a lesion-basis (SUVmean, SUVmax, tumor volume). A PET/MRI fusion was obtained, and agreement/disagreement was assessed visually, based on the overlapping lesion contours. WMHP slides were used to establish the disagreement of imaging-identified lesions with the gold standard pathology. Independent samples t-test and one-way ANOVA were used to assess group differences. Univariable and multivariable logistic regression models were used to assess the association of clinical, pathological, and imaging variables with PSMA-PET and mpMRI agreement/disagreement with each other and with pathology. Results: The cohort included 114 patients, and 175 pathology lesions were identified (ISUP 3, n=22; ISUP&gt;3, n=153). mpMRI and PSMA PET identified 138 and 170 lesions, respectively. Sensitivity for ISUP&gt;3 lesions was 79% and 87% for mpMRI and PSMA-PET, respectively. 115/153 (76%) ISUP&gt; 3 lesions were correctly identified, and 14/153 (9%) were missed by both imaging modalities, respectively. 5/153 (3%) were correctly identified by mpMRI and missed by PSMA-PET, 17/153 (11%) were correctly identified by PSMA-PET and missed by mpMRI. Lesion’s ISUP grade group and size on pathology were significantly lower in mpMRI- compared to mpMRI+ and in PET- compared to PET+ lesions. SUVmax and SUVmean were significantly higher in PET+/MRI+ than PET+/MRI- lesions. Lesion’s ISUP grade group and size were significantly correlated to PSMA-PET and mpMRI agreement, whereas PSMA-PET metrics were not. Logistic regression model showed that lesions with lower ISUP, smaller size, and lack of aggressive prostate cancer features on pathology (cribriform pattern and intraductal carcinoma) have higher likelihood of being missed by PET and mpMRI and of PET/MRI disagreement. Conclusions: Higher SUVmax, SUVmean, and tumor volume on PSMA-PET were associated with a TP finding on PSMA-PET, higher ISUP grade group and size on pathology were associated with a TP finding on both PSMA-PET and mpMRI, and with agreement between PSMA-PET and mpMRI.

A randomized phase II trial of neoadjuvant chemokine modulation in patients with localized prostate cancer undergoing radical prostatectomy.

340 Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). A high intra-tumoral CD8+ T lymphocyte density is associated with improved survival post-RP,1 suggesting possible clinical benefit from neoadjuvant chemokine modulation (CKM).2,3 We present the interim results of a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP were randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (Arm A: rintatolimod + aspirin + IFN-α: “Complete CKM regimen”) vs CKM doublet (Arm B: rintatolimod + aspirin) vs no CKM (Arm C). Methods: Thirty patients (10 per arm) are to be enrolled to assess CD8+ T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations represent secondary endpoints. Correlative blood studies analyzed the pre- vs post-CKM changes in Granzyme B (GrB; marker of effector/cytotoxic function in CD8+ T cells and FoxP3 (Treg marker) in CD4+ T cells. Results: The trial has enrolled 11 patients thus far (N=5 Arm A, 3 Arm B, 3 Arm C). There were no clinicopathological differences between the groups. Eight patients (on Arms A and B) were analyzed for changes in cytotoxic T cell numbers (CTL-D: GrB+CD8+ T-cells) in the blood. In Arm A, the mean pre-CKM CTL-D was 35.5% (±23.2%) and post-CKM was 47.7% (± 32.5%), while in Arm B, respectively, 37.9% (±22.2%) vs 37.1% (± 21.6%). These changes were reflected in the increased CTL/Treg markers in the post-treatment samples of patients on Arm A. These data indicate the ability of the “complete CKM regimen” (Arm A) to selectively enhance the CTL effector function in circulating CD8+ T cells, without enhancing the Treg markers. CKM regimen was well tolerated with no Grade 3 or above adverse events (AEs). Conclusions: In this interim analysis, treatment in all arms was feasible and safe. CTL-D and CTL-D/Treg in Arm A (“complete CKM”) shows an increasing trend over the course of CKM treatment. The levels of CTL-D in the resected prostate tissues are being currently evaluated. The study continues recruiting patients. 1. Yang, Y et al (PMID 33085799). 2. Muthuswamy, R et al (PMID 27199259). 3. Theodoraki, MN et al (PMID 29853604). Clinical trial information: NCT03899987 .

Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature.

Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with "carcinoid-like" features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.

Abstract A006: Cancer origin tracing and timing in two high risk prostate cancers using multisample whole genome analysis: Potential clinical value

Abstract Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Understanding the evolution of an individual PrCa through serial analysis in space and time may be more important than identifying actionable targets for therapy from single samples as in current practice. The most prominent recent example of this is our recent evolution-based discovery of subclone eradication in a metastatic PrCa, with subsequent identification of a novel method to compare eradicated and resistant subclones to better resolve actionable targets for therapy. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question. We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones. In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, five years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, three years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance identification of key drivers. Evolutionary analysis’ potential impact on therapy selection appears positive in these pilot cases. Taken together with our recent discovery that solid tumor subclones can be eradicated, and that comparison of eradicated and resistant subclones could guide therapy, we believe the case for embarking on clinical trials testing evolutionary-analysis informed PrCa care is compelling. PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value. Citation Format: Anssi Nurminen, Serafiina Jaatinen, Sinja Taavitsainen, Gunilla Högnäs, Tom Lesluyes, Naser Ansari-Pour, Teemu Tolonen, Kerstin Haase, Antti Koskenalho, Matti Kankainen, Juho Jasu, Hanna Rauhala, Jenni Kesäniemi, Tiia Nikupaavola, Paula Kujala, Irina Rinta-Kiikka, Jarno Riikonen, Antti Kaipia, Teemu Murtola, Teuvo L. Tammela, Tapio Visakorpi, Matti Nykter, David C. Wedge, Peter Van Loo, G. Steven Bova. Cancer origin tracing and timing in two high risk prostate cancers using multisample whole genome analysis: Potential clinical value [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A006.

Size of lymph-node metastases in prostate cancer patients undergoing radical prostatectomy: implication for imaging and oncologic follow-up of 2705 lymph-node positive patients

BackgroundDespite modern imaging modalities, lymph-node staging before radical prostatectomy (RP) remains challenging in patients with prostate cancer (PCa). The visibility of lymph-node metastases (LNMs) is critically influenced by their size.ObjectiveThis study aims to describe the distribution of maximal tumor diameters (i.e., size) in LNMs of pN1-PCa at RP and its consequences on visibility in preoperative imaging and oncological outcomes.Design, setting, and participantsA total of 2705 consecutive patients with pN1-PCa at RP, harboring a cumulative 7510 LNMs, were analyzed. Descriptive and multivariable analyses addressed the risk of micrometastases (MM)-only disease and the visibility of LNMs. Kaplan–Meier curves and Cox analyses were used for biochemical recurrence-free survival (BCRFS) stratified for MM-only disease.ResultsThe median LNM size was 4.5mm (interquartile range (IQR): 2.0–9.0 mm). Of 7510 LNMs, 1966 (26%) were MM (≤ 2mm). On preoperative imaging, 526 patients (19%) showed suspicious findings (PSMA-PET/CT: 169/344, 49%). In multivariable analysis, prostate-specific antigen (PSA) (OR 0.98), age (OR 1.01), a Gleason score greater than 7 at biopsy (OR 0.73), percentage of positive cores at biopsy (OR 0.36), and neoadjuvant treatment (OR 0.51) emerged as independent predictors for less MM-only disease (p < 0.05). Patients with MM-only disease compared to those harboring larger LNMs had a longer BCRFS (median 60 versus 29 months, p < 0.0001).ConclusionOverall, 26% of LNMs were MM (≤ 2mm). Adverse clinical parameters were inversely associated with MM at RP. Consequently, PSMA-PET/CT did not detect a substantial proportion of LNMs. LNM size and count are relevant for prognosis.

High expression of Trop2 is associated with aggressive localized prostate cancer and is a candidate urinary biomarker

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.