Adenocarcinoma Of The Prostate Research Articles

Abstract C090: High GLUT1 membrane expression and low PSMA membrane expression in ductal adenocarcinoma and intraductal carcinoma of the prostate

Abstract Background: Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis and can be lethal. Furthermore, previous studies linked aggressive clinical behavior and poor prognosis with discordant FDG positivity and low Prostate-specific membrane antigen (PSMA) expression. A recent study only cited a DAC patient with low 68Ga-PSMA-11 PET/CT uptake but high 18F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. IDC-P has similar cribriform pattern in the pathological structure as a mean differential diagnosis for DAC. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients. Methods: The study was conducted on 87 DAC or IDCP patients without any treatment and 97 PAC patients with a Gleason score ≥ 8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1. Results: PSMA expression in PAC tissues was significantly higher than in DAC/IDC-P tissues (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA membrane expression between DAC/IDC-P and adjacent acinar adenocarcinoma (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P tissue than in acinar adenocarcinoma tissue adjacent to DAC/IDC-P (68.6 vs 51.3, p = 0.007), but was still lower than that in PAC tissue (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in PAC (13.0 vs 6.6, p = 0.025), and in acinar adenocarcinoma adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001). Conclusions: In DAC and IDC-P tissues, PSMA membrane expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC and IDC-P cells may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism. Citation Format: Xingming Wang, Xiaomei Gao, Lin Qi, Ye Zhang, Hongling Yin, Yu Gan, Yi Cai. High GLUT1 membrane expression and low PSMA membrane expression in ductal adenocarcinoma and intraductal carcinoma of the prostate [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C090.

UTILITY OF P63 IMMUNO-EXPRESSION IN DISTINGUISHING BENIGN MIMICKER LESIONS FROM ADENOCARCINOMA PROSTATE-AN OBSERVATIONAL ANALYTICAL STUDY

In men, prostate cancer (PCA) is the second most common malignancy and is the sixth leading cause of death amongst them. Differentiation of benign mimicker lesions (BML) of the prostate from PCA can be challenging sometimes, especially when limited amount of tissue is available. Several immuno-histochemical (IHC) markers are recommended for distinguishing such lesions; which becomes expensive for the patient. The present study was planned to study the utility of P63 IHC marker for diagnosis of benign, BML and adenocarcinoma of the prostate (ACP). The present - observational and analytical study - was conducted on 50 biopsy specimens of the prostate in the Department of Pathology at IIMSR, Lucknow during the period January 2017 to September 2022. The lesions included were: 20 specimens of benign prostatic hyperplasia (BPH), 17 of BML, 3 of prostatic intraepithelial neoplasia (PIN) and 10 of PCA. In the BML group, 5 specimens of basal cell hyperplasia (BCH), 4 specimens of simple atrophy (SA), 3 specimens of post atrophic hyperplasia (PAH) and 5 specimens of adenosis were studied. In the present study, all specimens of BPH and BML are positive for P63 expression on IHC staining. In the PIN group, 2 out of 3 specimens were positive for P63. All 10 specimens of adenocarcinoma prostate were negative for P63 expression. We conclude that use of P63 IHC staining is adequate for distinguishing benign and BMLof prostate fromACPin majority of the specimens.

High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis, which were linked with discordant FDG positivity and low Prostate-Specific Membrane Antigen (PSMA) expression. A recent study only cited a DAC patient with low 68Ga-PSMA-11 PET/CT uptake but high 18F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients. The study was conducted on 87 DAC or/and IDC-P patients without any treatment and 97 PAC patients with a Gleason score ≥8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1. PSMA expression in PAC was significantly higher than in DAC/IDC-P (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA expression between DAC/IDC-P and adjacent PAC (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P than in adjacent PAC (68.6 vs 51.3, p = 0.007), but was still lower than that in pure PAC (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in pure PAC (13.0 vs 6.6, p = 0.025), and in PAC adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001). In DAC/IDC-P tissues, PSMA expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC/IDC-P may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism.

Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall.

The distinction of high-grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high-grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non-regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non-regional lymph-node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high-grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected.

Stable Therapeutic Transgenic FIX Levels for More Than 10 Years in Subjects with Severe Hemophilia B Who Received scAAV2/8-LP1-Hfixco Adeno-Associated Virus Gene Therapy

Background: Previously, we reported data from a first-in-human, dose-escalation, Phase 1 gene therapy trial demonstrating a dose-dependent increase in transgenic factor IX (FIX) expression in 10 adults with severe hemophilia B (FIX activity ≤1%). This was achieved following a single intravenous infusion of a self-complementary adeno-associated virus (scAAV) vector containing the wild-type FIX gene (codon-optimized), under the control of a synthetic liver-specific promoter and pseudotyped AAV8 capsid (scAAV2/8-LP1-hFIXco; ClinicalTrials.gov:NCT00979238). We now report durable efficacy and long-term safety over at least 10 years of follow-up in these participants. Methods: FIX activity, annualized bleeding rate (ABR), use of FIX concentrates, safety (specifically transaminitis and oncogenesis), and FIX expression kinetics were evaluated in the 10 participants following a bolus infusion of scAAV2/8-LP1-hFIXco at a dose of 2x10 11vg/kg (N=2), 6x10 11vg/kg (N=2), or 2x10 12vg/kg (N=6), between 2010 and 2012. Results: As of December 31, 2022, the median follow-up was 10.7 years (range 4-12 years). A total of 11 treatment-related adverse events occurred in 10 participants, including transient elevation of liver transaminases within 3 months of vector infusion in 4 of 6 patients treated with the high vector dose, without any recurrence. Two new serious adverse events were reported: (1) non-mucinous lung adenocarcinoma in situ, identified incidentally following a bullectomy for spontaneous pneumothorax 5 years after gene therapy in a 48-year-old participant considered not related to gene therapy following molecular studies, and (2) adenocarcinoma of the prostate in a 72-year-old participant 12 years after gene therapy. Tissue evaluation of the latter case is ongoing. No FIX inhibitors, thrombosis, persistent transaminitis or deaths were observed. Transgenic FIX expression has remained stable, with mean (±SD) FIX activity (one-stage) for the three dose cohorts of 1.7±0.9, 2.3±0.9 and 4.9±2.2 IU/dL, respectively (Figure 1). The mean and median ABR over the 10-year period following gene therapy of all 10 participants were 1.95 and 1.6 compared to 16.5 and 14, respectively, before gene therapy. This represents an 8.5-fold reduction in bleeding events (Wilcoxon signed rank test p=0.002). In the 6 high-dose participants, the ABR was 21-fold lower (mean=1.16, median 1, paired t-test, p&amp;lt;0.008). Mean and median FIX concentrate usage before gene therapy in the 10 participants were 2869 and 2526 IU/kg dropping to 945 and 274 IU/kg, respectively, over a 10-year period after gene therapy (p=0.0003). All participants developed a persistent, high-titer polyclonal anti-AAV8 capsid-specific antibody response after administration of scAAV2/8-LP1-hFIXco. Conclusion: Expression of transgenic FIX has remained stable over a period of 10 years following systemic administration of scAAV2/8-LP1-hFIXco resulting in sustained clinical benefit, with substantial reduction in ABR and FIX concentrate use.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Phase III Study of Hypofractionated, Dose Escalation Radiotherapy vs. Conventional Pelvic Radiation Therapy followed by High Dose Rate Brachytherapy Boost for High Risk Adenocarcinoma of the Prostate (PCS VI): Acute Toxicity Results

The low α\β ratio of 1.2-2 for prostate cancer (PCa) suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of lager fraction size. We have recently shown (PCS5) that high risk prostate cancer patients can safely and effectively be treated with moderate hypofractionated radiation therapy (HF-RT). To date there has been no phase-III randomized clinical-trial comparing moderately HF-RT with EBRT and HDR boost (HDRB). We are reporting the acute safety of EBRT+HDRB compared to moderate HF-RT in this phase III Canadian trial. From January 2015-June 2022, 308 high-risk localized PCa patients were randomized to receive either HF-RT or EBRT+HDRB. All patients received neo-adjuvant, concurrent, and long-term adjuvant androgen deprivation therapy (ADT). EBRT+HDRB consisted of 46 Gy in 2 Gy per fraction to the pelvis and a 15 Gy in one fraction HDR boost within 3 weeks of EBRT. HF-RT include concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate, and 45 Gy in 1.8 Gy per fraction to the pelvic lymph-nodes. Of the 308 patients, 148 received HF-RT and 144 EBRT+ HDRB. The remainder either withdrew from the study or were treated with standard (2 Gy per fraction) fractionation for technical reasons. In both intention to treat and as treated analysis, using log-Rank, there were more grade 1 or worse (G1+) acute GI and GU events and more G2+ acute GI events in the HF-RT than EBRT+HDRB. As treated analysis the acute G1+ and G2+ GI events were 92 vs 77 (60.1% vs. 53.5%; p < 0.017) and 21 vs 10 (13.7% vs. 6.9%; p = 0.052), respectively for HF-RT and EBRT + HDRB. Similarly, the G1+ acute GU events were 123 vs. 101 (80.4% vs.70.1%; p < 0.001) respectively for HF-RT and EBRT+HDRB. There were only four G3 GI and one G3 GU acute toxicities in both arms. No grade 4 toxicities were reported. This is the first study of EBRT+HDRB compared to moderate HF dose escalated RT in high-risk prostate cancer patients treated with long-term ADT and pelvic RT. Our results demonstrate that both treatment approaches are well-tolerated and that EBRT+HDRB carries less G2+ GI and G1+ GU acute toxicities.

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.

The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Heart transplantation and human immunodeficiency virus–navigating drug-drug interactions: a case report

BackgroundAntiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions.Case presentationA 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient’s immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30–35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy.ConclusionThe clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

Prostatic Metastasis Mimicking a Ligamentum Flavum Cyst in Thoracic Spine: A Case Report

A rare finding of a prostatic carcinoma metastasized in a ligamentum flavum at thoracic spine causing posterior column spinal cord compression. We reported a man with prostatic carcinoma presented with ataxic gait. Magnetic resonance imaging revealed an extradural cystic mass adjacent to the T4 intralaminar region indenting on the spinal cord. T4 posterior decompression via en bloc excision of the ligamentum flavum cyst and laminectomy was performed. Histopathology confirmed glandular tissue within the cyst wall which corresponds to prostatic adenocarcinoma cells. Two months post-operative, patient showed improvement in his muscle strength on left L2 myotome. The preoperative diagnosis is a challenge because of the ligamentum flavum cysts rarity in the thoracic spine and non-specific clinical signs and symptoms. To our best knowledge, this is the first report of metastatic adenocarcinoma of the prostate found as ligamentum flavum cysts.

Candida Prostatitis: A Review and Update

Candidiasis is a terminology that is used for a fungal infection that is caused by a yeast which is a fungus that called candida species. Some species of candida can cause infection in human beings and the commonest candida species that can infect human beings is candida Albicans. Candida normally lives upon the skin as well as inside the human body, such as the mouth, the throat, the gut, and the vagina, without causing problems. Candida can cause infections if it grows out of control or if it enters deep into the body. For example, it could cause infections in the bloodstream or internal organs like the kidney, the heart, or the brain. Candida infection can be localized to one body organ or it could be a disseminated candida infection affecting various organs. Candida infection does tend to afflict immune-supressed individuals more often in comparison with immune competent individuals. Candida prostatitis an uncommon condition which clinicians should have a high index of suspicion for because it does manifest with non-specific symptoms that tend to be associated with more common conditions of the prostate and the urinary tract. Candida infection of the prostate gland may be an isolated de novo infection or it may be associated disseminated candida infection, or it may also be associated with prostate cancer or various immune-suppression conditions. Candida infection of the prostate gland could manifest as an acute infection/inflammation of the prostate gland or a chronic inflammation of the prostate gland or it could manifest as prostatic abscess. Some of the potential manifestations of candida prostatitis and or prostatic abscess include: (a) incidental finding upon biopsy of the prostate gland or following trans-urethral resection of prostate gland or prostatectomy. ( b) patient may manifest with lower urinary tract symptoms, (c) a patient may manifest with urinary retention that may be acute or chronic, (d) a patient may manifest with raised levels of serum prostate specific antigen (PSA), € at times when digital rectal examination is undertaken on a patient who has Candida prostatitis, the prostate gland may feel benign and in the case of a candida prostatic abscess rectal examination may demonstrate bogginess in the area of the prostate with soft fluctuant feeling. (f) Eosinophil count in some cases of Candida prostatitis would tend to be normal but in some cases of candida infection of the prostate gland, there could be Eosinophilia but this would not be diagnostic of Candida infection, (g) a history of having had coital contact with an individual who has been treated for candida infection or a history of past treatment of the individual should alert all clinicians to exclude the possibility of candida prostatitis. (h) on rare occasions urine culture or culture of expressed prostatic secretions would yield a growth of Candida. Diagnosis of Candida infection or abscess of the prostate gland may be confirmed by positive culture of Candida in prostate biopsy specimen or resected or excised prostate specimen. Treatment of Candida Prostatitis / prostatic abscess does tend to entail: (a) Treatment with appropriate antifungal medicament, plus (b) Complete radiology image-guided aspiration / drainage of any abscess seen plus / minus or endoscopic deroofing trans-urethral resection of the prostate to ensure the abscess drains out completely. Because recurrence of Candida prostatitis or prostatic abscess or Candida infection elsewhere can occur, it is important for patients to have regular follow-up assessments to ensure recurrence disease does not develop and if it develops, it is diagnosed quickly in order to initiate prompt treatment. It is also important to assess all coital contacts of the patient to ascertain if they have Candida infection to enable prompt treatment of their infection. If an individual who has candida prostatitis or prostatic abscess is also found to have contemporaneous adenocarcinoma of the prostate, the carcinoma of the prostate gland should be treated appropriately based upon the Gleason Grade and the Stage of the carcinoma, the performance status and age of the individual patient based upon the national and international guidelines pertaining to prostate cancer as a separate multi-disciplinary team discussion of the patient management.

Analysis of survival and prognostic factors of clear cell adenocarcinoma of the prostate: a case–control study for a rare cancer entity

Clear cell adenocarcinoma of the prostate (CCPC) is a rare entity compared to acinar carcinoma of the prostate (APC). The survival rate and prognostic factors of CCPC are still unclear and deserve further study. We downloaded data on prostate cancer from the Surveillance, Epidemiology, and End Results database for 1975–2019. After inclusion and exclusion criteria, we compared APC and analyzed cancer-specific mortality (CSM) and overall mortality (OM) in CCPC patients and prognostic risk factors using a propensity score matching (PSM) study and multivariate Cox regression. We included 408,004 cases of APC as a control group and 130 cases of CCPC as a case group. Compared with APC patients, the incidence of CCPC was extremely low, and the median age of diagnosis was older (72.00 years vs. 69.00 years, p < 0.01). In addition, more rates were diagnosed at an earlier stage (1975–1998, 93.1% vs. 50.2%, p < 0.001), more unstaged or unknown stage ratios (87.7% vs. 42.7%, p < 0.001), and more surgical treatments (66.2% vs. 47.6%, p < 0.001), but the prognosis of CCPC patients was worse. After PSM, the median survival time of CCPC patients was shorter (57.50 month vs. 88.00 month, p < 0.01), the rate of CSM was higher (41.5% vs. 27.7%, p < 0.05), and the rate of OM was higher (99.2% vs. 90.8%, p < 0.01). In the adjusted model 2 after PSM, the CSM risk of CCPC patients reached HR 1.76 (95%CI 1.13–2.72), which was 76% higher than that of APC patients (p < 0.05). It was further found that surgical treatment might benefit CSM in CCPC patients (HR 0.39, 95%CI 0.18–0.82, p < 0.05) in Univariate analysis, but it was insignificant in further multivariate analysis. This is the first large-scale case–control report on the survival risk and prognostic factors of CCPC patients. We found that the prognosis of CCPC patients was significantly worse than that of APC. Surgery might be an effective treatment that may improve its prognosis. Clear cell adenocarcinoma, prostate, acinar carcinoma, survival rate, rare cancer, propensity score matching, case–control study.

Comedonecrosis within conventional prostatic adenocarcinoma vs. intraductal carcinoma of the prostate: their clinical significance is not comparable

It remains controversial if Gleason grade should be assigned to intraductal carcinoma of the prostate (IDC-P) and if the prognostic value of comedonecrosis associated with IDC-P is equivalent to that in conventional/invasive prostatic adenocarcinoma (CPA) as a Gleason grade 5 pattern. We herein assessed radical prostatectomy findings and postoperative outcomes in 287 patients with CPA exhibiting any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of necrosis within CPA and/or IDC-P: Cohort-1) no necrosis in CPA/IDC-P (n=179; 62.4%); Cohort-2) necrosis only in CPA (n=25; 8.7%); Cohort-3) necrosis only in IDC-P (n=62; 21.6%); and Cohort-4) necrosis in both CPA and IDC-P (n=21; 7.3%). Univariate analysis revealed patients with necrosis only in IDC-P (P<.001) or both CPA and IDC-P (P=.001) had a higher risk of progression than those with necrosis only in CPA, while the prognosis was comparable between the no necrosis group vs. the CPA only necrosis group (P=.680) or the IDC-P only necrosis group vs. the CPA/IDC-P necrosis group (P=.715). In a subgroup of patients exhibiting IDC-P (n=198), the presence of IDC-P necrosis was still associated with a significantly higher progression risk, compared with CPA necrosis only. In multivariable analysis, necrosis only in IDC-P (vs. necrosis only in CPA) showed significantly worse progression-free survival (HR=3.193, P=.003). IDC-P necrosis, as an independent predictor, was thus found to be associated with significantly worse oncologic outcomes, compared with necrosis only in CPA, and might therefore be better not to be simply considered as a grade 5 pattern.

Prostate-Specific Membrane Antigen Uptake Heterogeneity in Mixed Ductal-Acinar Adenocarcinoma of the Prostate.

Prostate-specific membrane antigen (PSMA) PET findings of mixed ductal-acinar adenocarcinoma of the prostate are rarely reported. We describe 18 F-PSMA-1007 PET/CT and delayed pelvic 18 F-PSMA-1007 PET/MRI findings in a case of prostatic mixed ductal-acinar adenocarcinoma with multiple lymph node and bone metastases. The primary tumor showed heterogeneous PSMA uptake. The metastases in the right ilium and acetabulum showed intense PSMA uptake, but the pelvic lymph node and left iliac bone metastases showed no significant PSMA uptake. Knowledge of the intraprimary and intermetastatic heterogeneity of PSMA uptake in mixed ductal-acinar adenocarcinoma of the prostate may be helpful for accurate interpretation.

Exploring the efficacy of a continuous form of the histologic grade in prostate cancer prognosis prediction.

e17105 Background: Adenocarcinoma of the prostate is the second most common type of cancer among men worldwide. The Gleason grading system remains the gold standard for evaluating the prognosis of prostate cancer by assessing the cancer morphology. However, the current discretized Gleason pattern regime limits the depiction of fine-grained histomorphological changes. We evaluated the efficacy of the algorithm-generated continuous histologic grade value in prostate cancer prognosis prediction. Methods: Whole-slide images of H&amp;E prostatectomy tissue, along with the follow-up data including new tumor event (NTE) and biochemical recurrence (BCR), were obtained for the cases diagnosed as prostate cancer during 2000-2013 from The Cancer Genome Atlas (TCGA) database. Cases with missing data were excluded, resulting in a total of 308 and 397 cases being used for the analysis of NTE and BCR, respectively. Our study utilized a deep learning-based algorithm that performs Gleason scoring as follows. First, it computes per-pixel likelihood values for each of the 4 classes: benign, Gleason 3, 4, and 5. Then, the per-pixel class with the highest likelihood value and the slide-wise ISUP grade group (GG-AI) is successively determined. We tweaked the algorithm to aggregate the likelihood-weighted Gleason grade assigned to each pixel into a continuous form of the histologic grade (c-HG). We compared the prognostic performance of c-HG with that of the original ISUP grade group in TCGA (GG) and that of algorithm-generated GG-AI in predicting the risk of NTE as well as BCR. The Cox regression analysis was conducted, setting the cases from one of three donating institutions (EJ, HC, KK) as the target, fitting the Cox model with the cases from the other institutions, and evaluating the fitted model on the target. Results: The median follow-up duration in months was 32 for NTE and 29 for BCR, respectively. The number of cases with NTE was 51, while the one with BCR was 82. The table presents the c-index values obtained from each institution for GG, GG-AI, and c-HG. Note that the number of cases in each institution is different for NTE and BCR, due to the different number of removed cases with missing data. c-HG showed the best average performance in both NTE and BCR risk predictions. It is also notable that c-HG showed a stable performance for varying institutions. Conclusions: We proposed an algorithm-based method of representing histologic grade as a continuous value, which may give better predictions in disease progression for prostate adenocarcinoma. [Table: see text]

A phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer: ARAMON study.

TPS5111 Background: Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration. In the phase 3 ARAMIS study (NCT02200614) of patients with nonmetastatic castration-resistant prostate cancer, treatment with darolutamide significantly improved metastasis-free survival and overall survival versus placebo, with a favorable safety profile. The incidences of central nervous system adverse events (AEs; e.g. falls, memory impairment, and depression) showed a ≤2% difference between the darolutamide and placebo groups. Fatigue was the only AE with an incidence of &gt; 10% for darolutamide (13.2% vs 8.3% for placebo). In a separate neuroimaging study of healthy volunteers, cerebral blood flow was not altered in patients treated with darolutamide but was significantly reduced in brain areas related to cognition in patients treated with enzalutamide. Furthermore, it is postulated that the low blood–brain barrier penetration of darolutamide may result in lower serum testosterone elevations than those seen with enzalutamide, with the potential of leading to fewer associated feminizing AEs. The objective of ARAMON (NCT05526248) is to compare the effect of darolutamide and enzalutamide monotherapy on post-treatment testosterone levels in patients with hormone-naive prostate cancer experiencing biochemical recurrence after definitive treatment for localized disease. Methods: ARAMON is a two-stage, open-label, phase 2 study of patients with histologically or cytologically confirmed adenocarcinoma of the prostate who have biochemical recurrence after radical primary prostatectomy or radiation therapy, with a prostate-specific antigen (PSA) doubling time of ≤20 months, baseline serum testosterone &gt; 150 ng/dL, and Eastern Cooperative Oncology Group performance status 0/1. During a 52-week lead-in phase, 25 patients will receive darolutamide 600 mg twice daily. If criteria based on serum testosterone increase from baseline to Week 12 are met, the study will proceed to a 52-week randomized phase in which the effects of darolutamide (600 mg twice daily, n = 20) will be compared with the effects of enzalutamide (160 mg once daily, n = 20). The primary endpoint of both phases is the change in serum testosterone level from baseline to Week 12. Secondary endpoints of the randomized phase include the change in serum testosterone levels from baseline to Weeks 24 and 52; PSA at Weeks 4, 12, 24, 36, and 52; changes in blood levels of markers for glucose, lipid metabolism, and endocrine function related to sex hormones; safety; and quality of life. Safety will be assessed through AE monitoring. The first of the 25 planned patients in the lead-in phase was enrolled on January 13, 2023. Clinical trial information: NCT05526248 .

8 - When tumor mass meets biopsy needle. the diagnostic and therapeutic challenge of ductal adenocarcinoma of the prostate: A rare case report

8 - When tumor mass meets biopsy needle. the diagnostic and therapeutic challenge of ductal adenocarcinoma of the prostate: A rare case report

Additional cycles of docetaxel in combination with androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Efficacy and feasibility analysis.

e17074 Background: Several phase III trials have assessed efficacy and safety of 6 cycles of docetaxel combined to androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). This is the current standard of care for a subgroup of patients. We aimed to assess whether treatment beyond 6 cycles of docetaxel prove to be more effective than the standard of care. Methods: We retrospectively collected data from patients with histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease treated at a large tertiary care center. All patients with mHSPC were treated in first-line with D-ADT (75 mg/m2) intravenously on the first day of each 21-day cycle. A subset of patients was treated beyond the standard of 6 cycles. Clinical and pathological variables were examined, as were treatment-related toxicities; progression free survival on D-ADT (PFS1), progression free survival on subsequent therapy (PFS2) and overall survival (OS) were calculated from start of treatment to progression or death by log-rank test. Results: Between 2015-2023 a total of 108 mHSPC patients were treated and observed for a median time of 13.8 months. Mean age was 66.2 years (range 46.9-82.7), and 75.0% had GS≥8, 65.7% a CHAARTED high-volume and 69.4% LATITUDE high risk disease. 72 pts. were treated with ≤ 6 cycles (D-ADTstand) (4.2% 1-2 cycles; 95.8 % ≥3 cycles; mean 5.2 cycles) and 36 were treated with &gt; 6 cycles docetaxel (D-ADTadd) (27.8% 7-8 cycles; 72.2% ≥9-10 cycles, mean 9.2 cycles). Frequency of toxicities did not differ in the groups. No significant differences were observed in median PFS1 (10.3 vs. 13.4 mos.) and PFS2 (6.3 vs. 6.6 mos.). Median OS in the D-ADTstand group was 39.8 mos., median OS in the D-ADTadd group was not yet reached. Conclusions: While more than 6 cycles of D-ADT in mHSPC proved to be feasible without significant additional toxicity, efficacy is not superior compared to the standard of 6 cycles. Overall survival data is not mature yet, but the benefit of more chemotherapy upfront is debatable and leverages further studies in light of the upcoming triplet combinations in mHSPC, that presumably will render doublet D-ADT obsolete in future. [Table: see text]

Characterization of Human Papilloma Virus in Prostate Cancer Patients Undergoing Radical Prostatectomy-A Prospective Study of 140 Patients.

The association between human papilloma virus (HPV) and the pathogenesis of prostate cancer (PCa) is still controversial. Existing studies often lack information about clinical risk factors, are limited by their retrospective design or only use a single detection method for HPV. A total of 140 patients undergoing radical prostatectomy (RP) for PCa at the Department of Urology, Ludwig Maximilian University of Munich, Germany, were prospectively enrolled. Knowledge of HPV and sociodemographic parameters were assessed with questionnaires. The following methods were used for HPV detection: RP specimens were tested for HPV DNA by PCR. If HPV DNA was detected, an LCD-Array hybridization technique was used for HPV subtyping, and immunohistochemical staining for p16 was performed as a surrogate marker for HPV infection. Serological titers of HPV-16 L1 antibodies were measured using an HPV-16-specific immunoassay. HPV DNA was detected in 9.3% (13/140) of RP specimens, with HPV-16 being the most predominantly detected subtype (5/13 = 39%). HPV-16 L1 antibody levels were below the limit of detection in 98% of patients (137/140). We found no significant difference between HPV PCR-positive (HPV+) and -negative (HPV-) patients in terms of HPV-16 antibody levels, history of HPV-associated diseases, level of education or marital status. Seventy-five percent of all PCa patients had never heard of HPV before. An acinar adenocarcinoma of the prostate was the most frequently detected histologic type in both HPV+ (100%) and HPV- (98%) patients (p = 0.86). HPV+ patients had fewer positive biopsy cores (3.5 vs. 5.8; p = 0.01) and a lower maximal tumor infiltration rate per core (37% vs. 57%; p = 0.03) compared to HPV- patients. However, when analyzing the whole prostate and the lymph nodes after RP, there were no significant differences in TNM stage, Gleason score or tumor volume between both groups. In a subgroup analysis of all high-risk HPV patients (n = 6), we found no significant differences in sociodemographic, clinical or histopathological parameters compared to HPV- or low-risk HPV+ patients. In our prospective study, we were not able to prove a clinically significant impact of HPV status on tumor characteristics in RP specimens. Most men with PCa had never heard of HPV, despite its proven causal association with other tumor entities.

Visualization of Intermetastatic Heterogeneity in Mixed Neuroendocrine Carcinoma-Acinar Adenocarcinoma of the Prostate by 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT.

Mixed neuroendocrine carcinoma-acinar carcinoma is an uncommon histological type of neuroendocrine prostate cancer. It has been rarely reported in de novo prostate malignancies. In this case, we present 68Ga-PSMA (prostate-specific membrane antigen), 68Ga-FAPI, and 18F-FDG PET/CT findings in the de novo form of mixed large-cell neuroendocrine carcinoma-acinar adenocarcinoma of the prostate. Different levels of radiotracer uptake were observed in different metastatic sites on 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT. This case demonstrates that the multitracer PET/CT strategy may be used for the noninvasive detection of the intermetastatic heterogeneity in metastatic neuroendocrine prostate cancer.