Adenocarcinoma Of The Prostate Research Articles

Prostate Type Malignancies Arising in Ovarian Teratomas - A Report of Two Patients.

The identification of benign prostatic tissue within ovarian and testicular mature teratomas is an unusual occurrence. While a few documented reports exist in the literature regarding the emergence of benign prostatic tissue within teratomas, the occurrence of prostatic-type adenocarcinoma in a mature ovarian teratoma is an exceptionally rare phenomenon. To date, only two prior reports have documented such instances, and no tumors have been previously reported with prostate-type tissue with morphologically two different malignancies. We outline our experience with two tumors involving prostatic-type carcinoma, both arising in ovarian mature teratomas. Microscopic examination of the first tumor revealed small areas of infiltrative atypical glandular proliferation within the mature teratoma. In the second tumor, prostate-type tissue exhibited a low-grade basal cell carcinoma. Additionally, adjacent minute foci of adenocarcinoma of the prostate (Gleason score 3 + 4 = 7, <5% pattern 4) were identified. Goblet cell adenocarcinoma of appendiceal type was also evident in the latter tumor. In both tumors, immunostains (NKX3.1, PSA) were performed to establish the prostatic origin of these atypical glands and PIN4 was performed to document the absence of basal cell in the atypical glands. On clinical follow-up, both patients have no signs of recurrence at 14 and 11 months after the surgery. Further reports on such neoplasms would contribute to a better understanding of the prognosis and management of such occurrences.

Utility of 64Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on 68Ga-PSMA-11 PET/CT.

Despite a high detection rate of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative 68Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog 64Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of 64Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal 68Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal 68Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. 64Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of 64Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4-11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28-2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). 64Cu-SAR-BBN PET-avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16-0.82). Patients were followed up for a median of 10 mo (IQR, 9-12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: 64Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.

Clinical-Grade Validation of an Autofluorescence Virtual Staining System With Human Experts and a Deep Learning System for Prostate Cancer

The tissue diagnosis of adenocarcinoma and intraductal carcinoma of the prostate includes Gleason grading of tumor morphology on the hematoxylin and eosin stain and immunohistochemistry markers on the prostatic intraepithelial neoplasia-4 stain (CK5/6, P63, and AMACR). In this work, we create an automated system for producing both virtual hematoxylin and eosin and prostatic intraepithelial neoplasia-4 immunohistochemistry stains from unstained prostate tissue using a high-throughput hyperspectral fluorescence microscope and artificial intelligence and machine learning. We demonstrate that the virtual stainer models can produce high-quality images suitable for diagnosis by genitourinary pathologists. Specifically, we validate our system through extensive human review and computational analysis, using a previously validated Gleason scoring model, and an expert panel, on a large data set of test slides. This study extends our previous work on virtual staining from autofluorescence, demonstrates the clinical utility of this technology for prostate cancer, and exemplifies a rigorous standard of qualitative and quantitative evaluation for digital pathology.

MpMRI features of mucinous prostate cancer: two case reports

BackgroundMucinous adenocarcinoma of the prostate (MACP) is one of the rarest variants of prostatic neoplasm, with more aggressive behavior than non-mucinous prostatic cancer. Previous studies suggested that these tumors exhibit different imaging magnetic resonance imaging (MRI) features compared with those of non-mucinous adenocarcinoma of the prostate upon which the conventional PIRADS v2.1 is based. To the best of our knowledge, this case series is the first to describe the multiparametric magnetic resonance imaging features of the MACP.ResultsWe presented two cases of biopsy proven mucinous adenocarcinoma of the prostate studied with multiparametric MRI. In both cases, diagnosis was late because of the different MRI features of MACP than those of the more common adenocarcinoma of the prostate. In both mpMRI, MACP appears to be hyperintense on T2WI, there was not a significant decrease in diffusivity in ADC maps and it exhibits early enhancement in DCE-MRI; the septa resulted in hypointense on T2WI compared to the PZConclusionsAccording to our experience, the conventional PIRADS v2.1 score is not suitable for mucinous prostate adenocarcinoma. MACP appears to be hyperintense on T2WI, has a lower ADC value, and exhibits early enhancement in DCE-MRI; the septa are usually hypointense on T2WI compared to the PZ. It is imperative for radiologists and urologists to be cognizant of this rare variant of prostate cancer to promptly identify and diagnose it, thereby preventing any diagnostic delays.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Prostate cancer with elevated free prostate-specific antigen density: A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide, and prostate-specific antigen (PSA) is often used in clinical practice to screen for prostate cancer. Normal total PSA (tPSA) level initially excludes prostate cancer. Here, we report a case of prostate cancer with elevated free PSA density (fPSAD). CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy, and the postoperative pathological results showed acinar adenocarcinoma of the prostate. The patient is currently undergoing endocrine chemotherapy. CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

Genomic profile of Japanese patients with rare ductal adenocarcinoma of the prostate has high grade and poor prognostic aspects.

e17046 Background: Ductal adenocarcinoma (DAC) is a rare subtype of prostate cancer with unknown etiology and poor prognosis. Genomic profile analysis using next-generation sequencing has the potential to elucidate the pathogenesis of rare cancers. To date, some studies have investigated the genetic profile of the DAC genotype; however, no definitive findings have been obtained due to the small number of patients and limited geographic coverage. The discovery of novel prognostic biomarkers and identification of new pharmacotherapeutic targets for DAC are currently of research interest. The aim of this study is to analyze the genomic profile of DAC in a Japanese population and to summarize its features. Methods: Clinical and histopathological records from our three hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens containing a DAC component in the past 10 years. Twenty-eight patients diagnosed with DAC of the prostate were identified, of whom 15 were eligible for genomic profile analysis and 10 patients (66.7%) had the pure type. Genomic evaluation was performed using either the FoundationOne CDx or PleSSision testing platform. Results: At least one genomic alteration occurred in 14 patients (93.3%), and the most frequently mutated gene was tumor suppressor protein p53 ( TP53), which was found in seven cases (46.7%). Additionally, five cases (33.3%) had mutations in retinoblastoma transcriptional corepressor 1 ( RB1), and all these patients had the pure type. Four cases had both TP53 and RB1 alterations, and most of these possessed the pure type and had PSA levels of less than 4.0. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 20.0%) and Wnt-β/catenin pathway (n = 6; 40.0%) was comparable, but alterations in the DNA damage repair (DDR) pathway were few (n=1; 6.7%). None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions: We found that the Japanese cohort with DAC has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1, and few DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of DAC, and further accumulation of cases is considered important.

#710 Rare manifestation of minimal change disease associated with prostate cancer

Abstract Background and Aims Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome as part of the paraneoplastic syndrome occurs in 11% of cases and is most often associated with membranous glomerulopathy. The association of minimal change disease (MCD) and prostate cancer is extremely rare, where only one case has been described in the available literature. Method We present the case of a 77-year-old patient who was admitted to the Transplantation-Nephrology Department of the University Hospital Martin with 3rd degree acute kidney injury and anasarca with fully developed nephrotic syndrome. Results During hospitalization, there was a gradual elevation of renal parameters and oliguria with the need for hemodialysis treatment. However, as part of the oncological screening, the level of prostate specific antigen was elevated (10.69 ng/l) with subsequent biopsy confirmed adenocarcinoma of the prostate in stage IIB (pT1cN0M0). Renal biopsy was performed with the finding of MCD, in light microscopy without pathological findings, with fully vital, normocellular glomeruli, without interstitial fibrosis and tubular damage, immunofluorescence without significant findings, in the electron microscope, pedicel podocyte fusions were present. Despite the generally valid recommendations for the treatment of prostate cancer of the given stage and age of the patient (follow-up), antiandrogen therapy was started in cooperation with the urologist along with the treatment of MCD with corticosteroids at a dose of 1 mg/kg. The patient experienced a significant improvement in renal parameters with the onset of diuresis without the need for dialysis treatment. Conclusion In the reported case, we describe a rare form of MCD associated with prostate cancer and a rare manifestation in the form of renal failure and the need for dialysis treatment with subsequent complete restitution of renal functions after KS treatment and antiandrogen treatment of the underlying oncological disease.

Body mass weighted prostate-specific antigen levels, new markers to predict locally advanced prostate cancer after prostatectomy.

Prostate-specific antigen (PSA) remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or body mass index (BMI), instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy. We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results. A total of 174 patients were diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N = 165) were considered to have localized disease on preoperative multiparameter magnetic resonance imaging. After prostatectomy, 73% (N = 127) of the patients remained in the localized disease group (group A) and 27% (N = 47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in group B (16.9 vs 11.2 ng/dL; p = 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA × body weight and PSA × BMI, a statistically significant difference emerged between the two groups ( p = 0.0198 in PSA × BW; p = 0.0110 in PSA × BMI). The body mass-weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.

Peritoneal Carcinosis, An Atypical Metastatic Site in Prostate Adenocarcinoma: A Case Report

Adenocarcinoma of the prostate is the second most common malignant tumour. It can spread in three ways: locally, via the lymphatic system or through the bloodstream. Diffuse peritoneal carcinosis is a rare entity during the evolution of prostate adenocarcinoma and only a few cases have been reported in the literature. This case report presents a patient with synchronous metastatic prostatic adenocarcinoma with peritoneal carcinosis. This case highlights the rarity of this type of prostate adenocarcinoma metastasis.

Inflammatory Patterns in the Prostate Gland and Serum Cytokine Activities in Primary Adenocarcinoma of the Prostate in Port Harcourt, Nigeria

Introduction: Chronic inflammation and pro-inflammatory cytokines such as (1L-6 and TNF-α) have been implicated in prostate carcinogenesis and metastasis. This study aims to evaluate serum concentrations of IL-6 and TNF-α, and to determine their association with clinicopathological patterns of prostate cancer in affected patients. Materials and Methods: Ninety (90) patients with histologically diagnosed prostate cancer (PCa), treated at the Urology Division of the University of Port Harcourt Teaching Hospital (UPTH), Nigeria were involved in this study. The enzyme-linked immunosorbent assay (ELISA) technique was used to assay cytokines (IL-6 and TNF-α), and serum PSA. Gleason Scores were categorized as well differentiated (GS of ≤ 6), moderately differentiated (GS = 7), and poorly differentiated (GS 8-10). Results were analyzed with IBM SPSS version 20.0. Pearson’s correlation test was used to determine the correlation between the cytokines (IL-6 and TNF-α) and Gleason Scores. Results: The modal age group with PCa was 60-69 years. The mean age of patients was 68.788.26 years, and the mean serum PSA 93.2478pg/ml. Serum levels of IL-6 and TNF-α were 8.0pg/ml, 11.2pg/ml and (27.0±26.4pg/ml) respectively. Forty-six subjects had poorly differentiated PCa (GS 8-10); 17 moderately differentiated (GS 7); and 27 well differentiated (GS ≤ 6). Mean serum levels of IL-6, TNF-α and PSA (113.1ng/ml) were raised and found highest in those with poorly differentiated PCa. Conclusion: The observed correlation was positive but weak. The patients might have commenced undeclared anti-inflammatory drugs that depressed inflammation. However, a larger sample size would probably confirm the prognostic value of IL-6 and TNF-α in PCa subjects.

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40Gy in 5 fractions given every-other-day and 27Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Saddle Pulmonary Embolus Treated With Bilateral Emergent Aspiration Pulmonary Thrombectomy

A 77 year old man with recurrent lower extremity thrombosis presented with acute onset shortness of breath and new onset hypoxemia three days after prostatectomy for adenocarcinoma of the prostate. He had been off anticoagulation during the perioperative period. In addition to his new diagnosis of prostate cancer he also had a remote history of treated non-invasive melanoma. Based on this presentation he was at high risk of developing thromboembolic disease. Computed tomography angiogram (CTA) of his chest confirmed a large saddle pulmonary embolus, echocardiogram was positive for new right ventricular wall motion dyskinesis and lower extremity ultrasound revealed bilateral acute and chronic deep vein thrombosis. Given his high bleeding risk, hypoxia and elevated troponin I, he underwent emergent successful aspiration pulmonary thrombectomy. This case is of interest to hospitalists and intesivists as it provides an overview of the current invasive management of pulmonary embolus in the acute setting when systemic anticoagulation is contraindicated. Emergent Aspiration Pulmonary Thrombectomy can restore pulmonary artery flow and cardiopulmonary hemodynamics. A collaborative team based approach that involves the emergency department, intensive care unit, interventional teams and hospitalists is favored.

Diffused Pulmonary Uptake of Tc-99m Methylene Diphosphonate Bone Scan in Patient with Prostate Cancer without Blood Test and Correlative/Cross-Sectional Imaging Abnormalities: A Case Report

Introduction: Bone scan using Tc-99m methylene diphosphonate (MDP) is a commonly used procedure for evaluating bone metastasis in cancer patients. Extra-osseous pulmonary uptake in bone scans is mostly an incidental finding and occurs in a multitude of disorders. Clinicians should be alert to any findings on clinical or complementary diagnostic tools. We presented a case of prostate cancer male patients who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan without any blood test and correlative/cross-sectional imaging abnormality Case Presentation: An 80-year-old male with adenocarcinoma of the prostate with a Gleason score of 6 (3+3). The PSA level was 0.009. The patient had a history of recurrent atrial fibrillation (AF), postural dizziness, HTN, Gout, and chronic renal failure, but all of these comorbidities were under control. The patient underwent a bone scan to annually check for the presence of bone metastases. Three hours after administering 740 MBq Tc-99m MDP intravenously. The reports didn’t show any increased uptake that would indicate metastases in the bones. Instead, diffuse bilateral pulmonary uptake and a mild increase in cardiac uptake were present. On the same day, a computed tomography (CT) scan of the thorax revealed 3 micro-nodules in the right upper lung that were described as benign lesions, and a chest X-ray confirmed normal results. The patient’s laboratory results were within normal range, and there were no clinical lung symptoms or complaints. Considering the patient history of persistent AF, chronic renal failure, and a complaint of postural dizziness, the bone scan finding may indicate involvement of amyloidosis. The relationship between amyloidosis and cancer was also widely noted. Conclusions: Tc-99m MDP may play a role in evaluating amyloidosis involvement in an uncommon place such as the lungs. Future research should focus on analyzing diagnostic options in the patient’s condition in this situation. Keywords: cancer, diffused pulmonary uptake, amyloidosis, bone scan

Abstract 1049: Prevalence of KDM6A expression loss in human cancer: A tissue microarray study on 6,560 cancers from 114 different tumor types

Abstract KDM6A, also known as UTX (ubiquitously transcribed X chromosome tetratricopeptide repeat protein) is an epigenetic regulator constituting a critical part of the COMPASS-like complex. KDM6A mutations occur commonly in cancer. These are of interest because KDM6A loss results in a dependency on EZH2, a potential therapeutic target. Most data on KDM6A have been obtained by next generation sequencing (NGS). However, since most KDM6A mutations are truncating and KDM6A is located on the X chromosome, many mutations result in a complete expression loss which can be detected by immunohistochemistry (IHC). To learn more on the prevalence of KDM6A expression loss and its role in cancer, a tissue microarray containing 6,560 samples from 114 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, KDM6A staining was rather ubiquitously seen in nuclei. In cancer, KDM6A staining was considered weak (1+) in 581 (11.2%), moderate in 1,927 (37%), and strong in 2,362 (45.4%) of 5,206 interpretable tumors. A complete loss of KDM6A staining occurred in 336 (6.5%) of tumors. At least one case with a complete KDM6A expression loss was observed in 51 of 114 tumor categories. KDM6A staining was most commonly lost in different categories of urothelial carcinomas (19.5-39.2%), squamous cell carcinomas of the esophagus (27.1%), hepatocellular carcinoma (18.4%), gastric carcinoma (3.2-12.5%), papillary renal cell carcinoma (9.5%), adenocarcinoma of the prostate (5.9-9.4%), chromophobe renal cell carcinoma (8.9%), Ewing sarcoma (8.3%), pheochromocytoma (8.3%), and metastatic malignant melanoma (8%). A KDM6A expression loss in less than 8% of cases was observed in 32 further tumor entities. KDM6A expression loss was more than twice as frequent in tumors from male (8.4% of 2,526) than in tumors from female patients (3.9% of 2,024; p&amp;lt;0.0001). It is concluded that KDM6A IHC is a suitable method for the detection of truncating KDM6A mutations, especially in males. These make up for about 2/3 of all KDM6A mutations and may exert specific biological effects than differ from the various KDM6A missense mutations known to also occur. Citation Format: Florian Viehweger, Natalia Gorbokon, Maximilian Lennartz, Viktor Reiswich, Florian Lutz, Till Krech, Andreas M. Luebke, Claudia Hube-Magg, Guido Sauter, Ronald Simon, Stefan Steurer, Andreas H. Marx, Christian Bernreuther, Martina Kluth, Sarah Minner. Prevalence of KDM6A expression loss in human cancer: A tissue microarray study on 6,560 cancers from 114 different tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1049.

Relation between Delay Time to Surgical Treatment of Prostate Cancer and Disease Recurrence Risk

Introduction: There is no consensus in the literature on a reasonable delay time from diagnosis to radical prostatectomy (RP) surgery, without worsening the prognosis. Objective: To evaluate the influence of the delay on the risk of disease recurrence in patients with acinar adenocarcinoma of the prostate treated with RP. Method: Four hundred and twelve patients undergoing RP were retrospectively evaluated. Of these, 172 were excluded due to incomplete data and another 28 due to preoperative staging as high-risk prostate cancer (PSA &gt; 10 ng/mL or Gleason score on biopsy &gt; 7). Pre-and postoperative stagings were compared and survival analysis was performed using the Kaplan-Meier method to investigate the influence of time on discordance between pre- and postoperative stagings. Results: For the 212 patients of the sample, the average time from diagnosis to RP was 176.1 ± 120.2 days (median 145.5 days), ranging from 29 to a maximum of 798 days. The Kaplan-Meier curve indicated that the cancer worsened the longer the delay between diagnosis and surgery. Patients undergoing surgery within 60 days had an approximately 95% probability of not increasing the initial risk of recurrence. This number fell to 80%, 70% and 50% in patients operated on up to 100, 120 and 180 days, respectively. Conclusion: Delay in performing RP represents a continuous risk of relapse. The ideal time for RP is up to 60 days from prostate biopsy, as the probability of upstaging is less than 5% in this period.

The prognostic value of ductal adenocarcinoma of the prostate in patients with advanced prostate cancer treated with abiraterone acetate.

167 Background: Previous studies have indicated that ductal adenocarcinoma of the prostate (DA) is associated with adverse prognosis in patients with localized prostate cancer (PCa). However, the clinical significance of DA in advanced PCa remains largely ambiguous. This study endeavors to investigate the relationship between the existence of DA in prostate biopsy specimens and treatment outcomes among patients with advanced PCa receiving abiraterone acetate (AA) therapy. Methods: We retrospectively analyzed data from 440 patients with advanced PCa who received AA at either the metastatic hormone-sensitive (mHSPC, N=123) or castration-resistant PCa (mCRPC, N=317) stage. The presence of DA and its proportion was evaluated based on prostate biopsy specimens. Kaplan-Meier curves and COX regression were used to evaluate the predictive significance of DA on AA efficacy, including PSA response, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS). Results: In aggregate, DA was detected in 35/440 (8.0%) patients, with 13/440 (3.0%) and 22/440 (5.0%) men harboring DA&lt;5% and ≥5%, respectively, in the total tumors. The overall PSA response rate in the entire cohort was 302/440 (68.6%), and it was comparable for people with and without DA, with both groups having a response rate of 68.6%. Of note, compared with patients without DA, men with DA have significantly longer median PSA-PFS (mPSA-PFS, 12.1- vs. 25.0-Mo, P=0.005) and median rPFS (mrPFS, 19.8 vs. 38.2-Mo, P=0.034). Subgroup analysis based on DA proportion further revealed that in comparison with PCa without DA, DA≥5% was an indicator of favorable PSA-PFS (HR, 95%CI: 0.28, 0.14-0.56, p&lt;0.001) and rPFS (HR, 95%CI: 0.35, 0.18-0.72, p=0.004), while DA&lt;5% was not. In multivariate COX regression analysis, after adjusting by clinicopathological factors, including mCRPC/mHSPC stage, ISUP grading, metastatic burden, pain score and pretreatment hemoglobin, alkaline phosphatase, and lactate dehydrogenase, DA≥5% was still independently associated with better therapeutic efficacy of AA treatment (PSA-PFS: HR, 95%CI: 0.36, 0.17-0.74, p&lt;0.001; rPFS: HR, 95%CI: 0.47, 0.23-0.96, p=0.040). Conclusions: A DA proportion ≥5% in the tumor is related to improved treatment efficacy for individuals with advanced PCa receiving AA. Thus, in the pathological diagnosis of PCa, it is necessary to routinely report the presence and proportion of DA in order to aid with treatment decision-making.

Construction and validation of a prognostic nomogram for ductal adenocarcinoma of the prostate: A population-based study.

This study aimed to establish and validate a nomogram for ductal adenocarcinoma of the prostate (DAC) to accurately predict the prognosis of DAC patients. The data of 834 patients with confirmed DAC were obtained from the Surveillance, Epidemiology, and End Results database. The cases were randomly assigned to the training and internal validation cohorts. Data from patients attending our institution as an external validation cohort (n = 35). Nomogram and web-based dynamic nomogram were constructed based on Cox regression analysis, and their prediction accuracy was evaluated by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis. Multivariate analyses identified age, T-stage, N-stage, M-stage, surgery, lymph node dissection, Gleason score, and PSA as independent prognostic factors for overall survival. The C-index and calibration curves demonstrate the good discriminative performance of the prediction model. The area under the curve further confirmed the accuracy of the nomogram in predicting survival. In addition, the area under the curve and decision curve analysis were better than the 7th tumor-node-metastasis staging system. The Kaplan-Meier curves of the nomogram-based risk groups showed significant differences (P < .001). We constructed and validated the first nomogram to predict patients with DAC.

Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study

Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. None.

Carboplatin and Etoposide for the Treatment of Metastatic Prostate Cancer with or without Neuroendocrine Features: A French Single-Center Experience.

Chemotherapy using carboplatin and etoposide (CE) is frequently pragmatically proposed to treat metastatic prostate cancer (mPC), both primary small-cell neuroendocrine (PSC-NE) carcinoma and adenocarcinoma with or without neuroendocrine (NE) marker elevation. However, the real benefit of CE is poorly reported in the recent therapeutic context. We retrospectively analyzed the efficacy and tolerance of CE chemotherapy in these three different groups of mPC patients. Efficacy endpoints included radiological response, progression-free survival (PFS), and overall survival (OS), as well as PSA response and PFS2/PFS1 ratio in patients with adenocarcinoma. Sixty-nine patients were included in this single-center study (N = 18 with PSC-NE carcinoma and 51 with adenocarcinoma with (N = 18) or without (N = 33) NE marker elevation). Patients with adenocarcinoma were highly pretreated with next-generation hormonal agents (NHAs) and taxanes. In patients with adenocarcinoma, a PSA response ≥50% was observed in six patients (15.8%), four of whom had NE marker elevation. The radiological response was higher in PSC-NE and tended to be higher in adenocarcinoma when NE marker elevation was present. Comparing patients with adenocarcinoma with vs. without NE marker elevation, the median PFS was 3.7 and 2.1 months and the median OS was 7.7 and 4.7 months, respectively. Overall, 62.3% of patients experienced grade 3-4 adverse events (mainly hematological), and three treatment-related deaths were recorded. Reports of the clinical results of CE suggest that we should not mix PSC-NE and castration-resistant adenocarcinoma of the prostate. In patients with heavily pretreated adenocarcinoma, the benefit/risk ratio of CE chemotherapy seems unfavorable due to poor response and high toxicity.