Metastatic Prostate Adenocarcinoma Research Articles

Update on the outcome of patients with metastatic prostate cancer in Kentucky: A Kentucky Cancer Registry (KCR) study.

e17121 Background: Overall survival (OS) of metastatic Prostate Cancer (mPC) in USA has improved by 3.6% during 2011–2016 compared to 2001–2005 (CDC, Oct 2020). Improvements in OS for mPC might reflect changes in clinical management, with approval of several new treatments. We aim to analyze if there is an improvement in OS of mPC in Kentucky between 2004-2011(T1) and 2012-2019(T2) and also analyze the impact of socioeconomic status as defined by Area Deprivation Index (ADI) on survival of mPC. Methods: All Kentucky male patients diagnosed between 2004 and 2019 who were > 20 years old at diagnosis with first primary of metastatic prostate adenocarcinoma were extracted from the Kentucky Cancer Registry (KCR) data. Basic demographics and survival outcomes were compared between two time periods - T1 vs T2 and by Appalachian status. Kaplan Meir (KM) and Multivariate Cox Regression (MCR) were used to examine OS. ADI is divided into three groups – bottom tertile (low deprivation-ADI 1-3, Gr 1), middle tertile (ADI 4-6, Gr 2), and top tertile (high deprivation-ADI 7-10, Gr 3). Results: A total of 2619 patients with mPC were included in this retrospective analysis, of which 69.3% were Non-Appalachian (Non-AP) and 30.7% were Appalachian (AP). Caucasians predominated in both time periods (89.2% vs 90%). T2 had a higher proportion of patients aged 50-74 years (72.5% vs 64.2%), and private insurance (31.4% vs 27.1%) compared to T1. T1 had more patients who were > 75 years (31.6% vs 24.8%), smokers (51.2% vs 47.4%), had medicare (59.6% vs 56.8%) and no insurance (4.2% vs 1.5%) compared to T2. KM showed improved OS in T2 (p < 0.0001). Non-AP had better OS compared to AP and improved more between T1 & T2. Median OS in months(95% CI) in T1 vs T2 for Non-AP was - 30(27-38) vs 58(53-69), p < 0.0001 & for AP was -34 (27-39) vs 44 (37-51), p = 0.0163. MCR showed that younger age, private insurance, being a nonsmoker, and receiving treatment, contributed to better OS. Gr 3 had higher proportion of African Americans (10.7% vs 6.5%), less private insurance (23.9% vs 39.7%) and more patients receiving no treatment (10.9% vs 7.5%) compared to Gr 1. AP Kentucky had more patients in Gr 3 (60.5% vs 39.5%) compared to Non-AP. KM showed OS had improved for all ADI groups in T2 vs T1. Within ADI groups, Gr 3 had significantly lower OS compared to Gr 1 & Gr 2 (p = 0.04) in T2. In T1, OS was not different within ADI groups. In MCR, race and ADI did not impact OS. Conclusions: OS has improved in mPC patients in Kentucky during 2012-2019, likely due to new treatments being available. There is improvement in OS in Appalachian Kentucky but numerically lower than Non-Appalachian, and worse OS in Gr 3 during 2012-2019 which could be partially due to differences in access to new treatments (or quality of care). Interestingly, race did not impact survival.

Immunogenomic Landscape of Neuroendocrine Prostate Cancer.

Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small-cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared with other prostate cancer types and SCLC. In this retrospective study, a cohort of 170 patients with 230 RNA-sequencing and 104 matched whole-exome sequencing data were analyzed. Differences in immune and stromal constituents, frequency of genomic alterations, and associations with outcomes were evaluated. In our cohort, 36% of the prostate tumors were identified as CD8+ T-cell inflamed, whereas the remaining 64% were T-cell depleted. T-cell-inflamed tumors were enriched in anti-inflammatory M2 macrophages and exhausted T cells and associated with shorter overall survival relative to T-cell-depleted tumors (HR, 2.62; P < 0.05). Among all prostate cancer types in the cohort, NEPC was identified to be the most immune depleted, wherein only 9 out of the 36 total NEPC tumors were classified as T-cell inflamed. These inflamed NEPC cases were enriched in IFN gamma signaling and PD-1 signaling compared with other NEPC tumors. Comparison of NEPC with SCLC revealed that NEPC had poor immune content and less mutations compared with SCLC, but expression of checkpoint genes PD-L1 and CTLA-4 was comparable between NEPC and SCLC. NEPC is characterized by a relatively immune-depleted tumor immune microenvironment compared with other primary and metastatic prostate adenocarcinoma except in a minority of cases. These findings may inform development of immunotherapy strategies for patients with advanced prostate cancer.

Case Report: Pulmonary Sequestration in an Adult Not A Metastasis

Introduction: Pulmonary sequestrum is a rare congenital lung anomaly defined as an area of dysplasia and nonfunctional lung tissue with abnormal systemic blood supply and various forms of venous drainage. We report the case of a 43-year-old man who was followed up for prostate adenocarcinoma with bone and lung metastases. The diagnosis of bronchopulmonary sequestration was made. Case report: The patient was 62 years old and was being followed for metastatic prostate adenocarcinoma to the bone. The frontal chest radiograph showed a poorly limited right basal opacity. Bronchial endoscopy noted an inflammatory appearance of the right lower lobar bronchus. A thoraco-abdomino-pelvic CT scan was requested as part of the extension work-up to identify a focus of intra-parenchymal condensation on the right posterior basal side vascularized by an abnormal systemic vessel emanating from the descending thoracic aorta in favor of an intra-lobar sequestration. Discussion and Conclusion: Pulmonary sequestration is a rare malformation whose diagnosis must be evoked in front of repeated infections in the same pulmonary territory, in particular the posterobasal territory. Multislice CT or MRI angiography are the examinations of choice for diagnosis and assessment. Surgical treatment remains the most important option.

Abstract 3437: Whole genome and transcriptome sequencing of a pan cancer cohort unearths novel therapeutic avenues

Abstract Whole genome sequencing (WGS) has emerged as a tool to characterize the entire genomic landscape of cancer and capture potential new targets and predictive biomarkers. Using state-of-the-art whole-genome and transcriptome sequencing (WGTS) analysis we interrogated a pan cancer cohort to nominate new treatment options. WGS was performed on 414 tumor/germline pairs from our pan cancer cohort of 355 patients, of which 103 had results of other commercial NGS assays. RNAseq data was available in 96 samples. We employed the Isabl GxT analytic platform and manually curated single base substitution (COSMIC v3) mutational signatures and structural variants (SVs). WGTS results were correlated with available clinico-pathologic data. High throughput drug screening that included PARP inhibitors and functional validation were performed in 61 matched patient-derived tumor organoids (PDTO). We found 5,129 SVs affecting at least one cancer gene in 88% of cases. High-confidence homologous recombination deficiency (HRD), determined by curation of mutational signatures and mutations/SVs affecting oncogenes and tumor suppressor genes, was detected in 8.3% of solid tumors (e.g., prostate, pancreas, ovarian, uterine, breast, gallbladder, and stomach carcinomas). HRD status included tumors with BRCA1/2 wildtype and SVs impacting BRCA1/2, RAD51, ATM and other HRD genes. CDK12-loss associated genomic instability was detected in 7 cases including 3 cases of prostate adenocarcinoma. 93 gene fusions involving cancer genes were detected including known and novel fusions of potential significance (e.g., SLC45A3::ALK in metastatic prostate adenocarcinoma, TMEM106A::BRCA1 in serious ovarian carcinoma, ESR1::EP300 in metastatic breast cancer). Some tumor cohorts demonstrated enrichment of drivers e.g., FGFR1 amplification in male breast cancer, rearrangements at the TERT locus in adrenocortical carcinoma, enrichment for repeat-mediated deletion attributed to mismatch repair (MMR) in gynecological carcinosarcoma, and SVs affecting FHIT in gastric adenocarcinoma. Drug screening of PDTO and functional testing with RAD51 immunofluorescence assay validated high-confidence HRD annotation. One example is a BRCA1/2 wildtype pancreatic adenocarcinoma with increased tandem duplications and SV (inversion) impacting BRCA2, and high-confidence HRD by our novel WGS classifier. Drug screening of the corresponding PDTO showed an enhanced response to Olaparib, in contrast to cases without HRD that did not. We have used state-of-the-art analysis of WGTS to improve the detection of targets and significant biomarkers in a pan cancer cohort, including HRD, CDK12-type genomic instability, pathogenic germline mutations and potential targetable novel fusions. A robust and clinically relevant ex vivo preclinical model allowed us to validate a WGS-based classifier that detects HRD even in cancers with wildtype BRCA1/2. Citation Format: Majd Al Assaad, Hui-Hsuan Kuo, Jones Nauseef, Max F. Levine, Gunes Gundem, Juan S. Medina-Martínez, Jyothi Manohar, Michael Sigouros, Ahmed Elsaeed, David Wilkes, Elli Papaemmanuil, Eloise Chapman, Scott T. Tagawa, Allyson Ocean, Cora N. Sternberg, Eleni Andreopoulou, Manish Shah, Andrea Sboner, Kevin Holcomb, David Nanus, Laura Martin, Olivier Elemento, Juan Miguel Mosquera. Whole genome and transcriptome sequencing of a pan cancer cohort unearths novel therapeutic avenues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3437.

Abstract 4345: Molecular pathology studies reveal PD1+ CD8 T cell density correlates with response to supraphysiological testosterone treatment in pre-treatment biopsies and MYC mRNA and protein correlate with response after treatment

Abstract While most patients with metastatic prostatic adenocarcinoma respond initially, nearly all develop resistance to multiple lines of androgen deprivation therapies. This is related to overexpression of the androgen receptor (AR), which is frequently driven by AR amplification. In some patients, increased AR renders tumor cells sensitive to high dose androgens which paradoxically inhibits their growth. Bipolar Androgen Therapy (BAT) was introduced in which patients with castration resistant prostate cancer (CRPC) are treated intermittently with high dose testosterone. This produces biochemical and objective responses, and may re-sensitize prostate cancer to subsequent second generation AR inhibitors. This study utilizes samples from a recently performed clinical trial for patients with CRPC that included sequential biopsies of soft tissue metastases before BAT and after 3 cycles of BAT and before patients were treated with nivolumab.Tumor cells were present in FFPE blocks for both the pretreatment and C4D1 time points for 24 of the patients. These FFPE samples were stained using a recently validated iterative multiplex IHC assay containing 6 antibodies including: CD3 (T cells), CD4 (Helper T Cells), CD8 (Cytotoxic T Cells), PD1 (T Cell Checkpoint), FOXP3 (T-Reg cells), and Keratin 8 (epithelial cell marker). Biopsy slides were scanned after each round of staining and whole slide scans were imported into the HALO image analysis where they underwent color deconvolution, image registration and fusion. Regions of tumor were demarcated manually, and computerized automated image analysis was used to determine cell densities for 8 cell phenotypes (total CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+Foxp3+, CD3+CD4+PD1+, CD3+CD8+PD1+, CD3+CD4+PD1-, CD3+CD8+PD1-). There was a higher density of CD3+CD8+PD1+ cells in the pretreatment biopsies of men who responded (R) (to BAT) as compared with those who did not respond (NR)(p=0.015 Wilcoxon rank-sum test; mean 92.7 [R] vs 13.9 [NR]). The difference in R vs. NR was less and not significant in the CD3+CD8+PD1- population. There was a trend towards a higher density of CD3+CD4+PD1+ cells in the pretreatment samples in responders, but less so in the CD3+CD4+PD1- population. In the C4D1 biopsies, only CD3+ total cells were significantly higher in the R vs. NR (P=0.02), but the other phenotypes were not. We conclude that increased density of CD3+C8+PD1+, but not CD3+CD8+PD1- cells was present in pre-treatment biopsies in responders as compared with non-responders to BAT. These results indicate that men who are likely to respond to high dose testosterone treatment harbor tumors that are immunologically distinct prior to treatment than those men unlikely to respond. Additional spatial analysis and comparisons with RNAseq data will be presented. Citation Format: Carolina Gomes Alexandre, Jessica Hicks, Tracy Jones, John T Isaacs, Kiara Bowers, Alyza Skist, Laura Sena, Jennifer Meyers, Emmanuel Antonarakis, David Sanin, Hanfei Qi, Samuel Denmeade, Mark Markowski, Srinivasan Yegnasubramanian, Angelo De Marzo. Molecular pathology studies reveal PD1+ CD8 T cell density correlates with response to supraphysiological testosterone treatment in pre-treatment biopsies and MYC mRNA and protein correlate with response after treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4345.

Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer.

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the activation and infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the antitumor efficacy of immunotherapies using immune checkpoint blockade (ICB), adoptive cell transfer, or agents inhibiting myeloid-derived suppressor cells. In human prostate cancer samples, Pygo2 expression was inversely correlated with the infiltration of CD8+ T cells. Analysis of the ICB clinical data showed association between high PYGO2 level and worse outcome. Together, our results highlight a potential path to improve immunotherapy using Pygo2-targeted therapy for advanced prostate cancer.

Extra-cardiac uptake of 99mTc-pyrophosphate scan leading to the diagnosis of stage IV metastatic prostatic adenocarcinoma.

Extra-cardiac uptake of 99mTc-pyrophosphate scan leading to the diagnosis of stage IV metastatic prostatic adenocarcinoma.

Genomic profiling between Hispanic Americans (HA) and non-Hispanic (NHW) with advanced prostate cancer: A retrospective analysis of tissue, liquid, and germline testing.

30 Background: Genomic testing through the employment of somatic and germline testing has become increasingly relevant in determining the prognosis and targeted therapies for advanced prostate cancer patients. Prostate cancer health disparities resulting in worse presentations and clinical outcomes have been observed in HA compared to NHW. Understanding the prevalence of different genomic alterations is paramount to bridge the gap between the two ethnic groups. Methods: This is a retrospective analysis of 190 metastatic prostate adenocarcinoma patients with 24.2% HA who presented to the University of Arizona Cancer Center from 2015 to 2022. Patients in both groups may have undergone more than one type of testing. Homologous recombination repair (HRR) included ATM, BRCA1/2, BARD1, BRIP1, CDK12, CHEK1/2, FANCA/L, HDAC2, PALB2, RAD-51B/1C/51D, or 54L. Tissue-agnostic therapy approvals are dMMR, MSI-H, TMB-High, BRAF V600E, and NTRK/RET fusion. The proportion of HA and NHW was determined, and the statistical significance of the differences was reported using Chi2 or Fisher’s Exact test. Results: 43.6%, 34.7%, and 38.9% of patients had somatic tissue, liquid, and germline testing, respectively analyzed for pathogenic variants. TMB-High &gt;10 (30% vs 3.6%, p=0.02), PD-L1 CPS&gt;5 (9.4% vs 0%, p=0.03) and TMPRSS2-ERG fusion (37.5 vs 7.8%, p=0.0009) had higher proportion in HA compared to NHW. No test showed a difference in BRCA 1/2 or another HRR deficiency actionable mutation between the two ethnicities. There were no other statistically significant differences in common mutations or variants of unknown significance among groups. Conclusions: Liquid and tissue biopsies indicated a difference in proportions for tissue-agnostic and immune-oncology therapeutic indications, being more prevalent in HA. TMPRSS2-ERG fusions have differences in PC development and progression by race and now potentially by ethnicity, as shown by our study. Our review revealed increased germline and somatic testing over time according to targeted therapies approval and guideline recommendations, although, there remains a critical need for advancing genomic sequencing efforts for underrepresented HA. The Hispanic Americans Prostate Cancer Comprehensive Genomic Profiling Study's (THAPCA-GPS) future investigations aim to delineate the pathogenetic differences between HA and NHW and may reduce healthcare disparities and improve clinical outcomes in HA patients. [Table: see text]

Enzalutamide-Induced Acute Maculopapular Rash in Treatment of Metastatic Prostate Cancer: First Case Report from a Tertiary Cancer Care Center of North India.

Enzalutamide is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013.We report a case of acute generalized exanthematous maculopapular rash induced by enzalutamide. In summary, newer androgen receptor blockers have a propensity to cause skin related adverse effects. Most common among these are apalutamide. Enzalumatamide, per se, is a safe drug and has not been associated frequently in causing maculopapular rash. Few cases has been reported. In all these cases, the drug was discontinued and 2nd line therapy was instituted. In this report, Enzalutamide was withheld for 10 days and anti-histaminics was instituted. After a full recovery, Enzalutamide was reinstituted in treatment.A 62-year-old male patient with no significant medical history, was diagnosed in March 2020 with metastatic prostatic adenocarcinoma. Baseline PSA was 456 ng/ml. PSMA PET scan showed evidence of multiple bony metastasis. He was started on Degarelix subcutaneous injection with oral abiraterone initially. PSA level showed initial decreasing trend till September 2021 followed by sudden increase. Intramuscular Injection leuprolide was started and initial responses were good followed by later rise of PSA from January. Tab Xtandi (Enzalutamide) was added to the regimen from 31.1.22. Three days after starting enzalutamide treatment, the patient experienced an acute skin reaction. It is about of the plaques covered with widespread millimetric non-follicular papules. Enzalutamide was stopped after appearance of rashes to avoid further serious adverse effects. Anti-histaminics were started. Complete resolution of skin lesions occurred within 10 days. Tab Enzalutamide was reinstituted on 11th day after stoppage and on complete resolution of skin resolutions. According to the CTCAE 5.0 criteria, these skin rash was graded as grade 2. In view of evidence in literature and clinical improvement after stoppage, the acute drug reaction was attributed to enzalutamide.Uro oncologist can be confronted with adverse skin drug reactions attributable to new therapeutic molecules. The slow resolution of symptoms seems be due to the long half-life of enzalutamide. It should not be withdrawn from therapy owing to these effects. Rather, it should be with stopped for 10-14 days. Basic treatment with anti-histaminics or topical steroids may be enough to warranty the resolution of symptoms, and the drug (Enzalutamide) can be continued thereafter.

Evaluation of Gabapentin as a Treatment of Breakthrough Cancer Pain Caused by Metastatic Prostate Adenocarcinoma.

Breakthrough Cancer Pain (BTcP) is defined as a temporary increase in pain that occurs spontaneously. The use of gabapentin is believed to be able to reduce pain complaints in patients with BTcP. However, research to support the efficacy of gabapentin in relieving pain in patients with BTcP is still limited. This study aims to determine the effectiveness of the use of gabapentin in patients with BTcP caused by metastatic prostate adenocarcinoma. The study was conducted by analytic study with a prospective approach. The subjects were all patients with metastatic prostate adenocarcinoma at Zainoel Abidin General Hospital during 2022-2023 which fulfilled inclusion and exclusion criteria (30 patients). Data analysis was performed in the form of reduction in pain scale in patients with BTcP caused by metastatic prostate adenocarcinoma using gabapentin and the combination of the opioid gabapentin with T-Test. The results showed that there was no significant difference between the reduction in posttreatment pain in patients with BTcP caused by metastatic prostate adenocarcinoma taking gabapentin alone or taking the opioid gabapentin combination, either on days 3-4 or on days 5-6 (p > 0.05). However, based on the results of the evaluation on day 3-4, it was found that gabapentin was able to reduce pain by 2.2272, whereas the combination of opioid gabapentin was only able to reduce pain by 1.916. The evaluation on days 5-6 showed that gabapentin was able to reduce pain by 4.1363 and the combination of gabapentin opioids by 3.2083. The conclusion of this research is that gabapentin is effective in the treatment of BTcP caused by metastatic prostate adenocarcinoma.

Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer.

A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and 68Gallium-DOTATATE PET-CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome. Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described. Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload. Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer. More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome. Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

Bisphosphonate related osteonecrosis of the jaws associated with denture and dentoalveolar surgery

OBJECTIVES: The aim of this article was to present and discuss the diagnosis, management, and follow-up of a patient treated with zoledronic acid because of a metastatic prostate adenocarcinoma, that developed bilateral mandibular ONJ. DISCUSSION: Biphosphonates are synthetic analogues of pyrophosphate. Two types of biphosphonates share a common phosphorus-carbonphosphorus backbone: alkylbiphosphonates, such as clodronate, etidronate … Continued

A lncRNA-immune checkpoint-related gene signature predicts metastasis-free survival in prostate adenocarcinoma.

The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease biology. However, the role of immune checkpoint genes (ICGs) in PRAD remains unclear. Univariate and multivariate analyses were used to analyze genes associated with metastasis-free survival (MFS) in The Cancer Genome Atlas (TCGA)-PRAD dataset. The expressions of ADORA2A and TNFRSF18 were detected via immunohistochemical assay and real-time fluorescence quantitative PCR (RT-PCR) assay in our in-house cohort. The expression of long non-coding RNAs (lncRNAs) AL139287.1, SLC9A3-AS1, and SNHG12 were detected via RT-PCR assay in our in-house cohort. Stepwise regression, Cox regression, and nomogram analyses were used to evaluate the prognostic role of these genes in both the TCGA dataset and in-house cohort. The "pRRophetic" R package was used to evaluate drug sensitivity in the TCGA cohort according to the gene mRNA expression level. In our study, univariate and multivariate analyses revealed that the mRNA expressions of two ICGs, ADORA2A and TNFRSF18, were independent factors affecting MFS in PRAD patients. A prognostic 2-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. The expressions of AL139287.1, SLC9A3-AS1, and SNHG12 were correlated with ADORA2A and TNFRSF18. A prognostic lncRNA-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. In addition, correlation analyses between the sensitivity of doxorubicin, erlotinib, gemcitabine, or vinorelbine and AL139287.1, SLC9A3-AS1, SNHG12, ADORA2A, and TNFRSF18 were conducted. Our results provide new targets for predicting tumor metastasis in PRAD and treating patients with metastatic PRAD.

A Fixed-Duration Immunochemotherapy Approach Combined with Ibrutinib in CLL Produces Deep and Sustained MRD Responses: 5.5-Year Results from the Icll-07 Filo Trial

Introduction In previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), the availability of targeted agents has led to research interest in achieving deep, durable remissions and improving survival outcomes. The phase II ICLL-07 (NCT02666898) trial by the French Innovative Leukemia Organization (FILO) evaluated a fixed-duration (15-month) immunochemotherapy approach (no more than 4 fludarabine/cyclophosphamide [FC]-obinutuzumab cycles). Primary analysis showed the approach was safe and 62.2% (84/135) of all patients enrolled achieved complete response (CR) with bone marrow (BM) minimal residual disease (MRD) <0.01% (Michallet et al Lancet Haematol 2019;6:e470-9). Follow-up at median 37 months from treatment start showed a persistent MRD benefit beyond end of treatment, high survival rates, and low long-term toxicity (Michallet et al Blood 2021;137:1019-23). Here we report long-term results at median 64 months from treatment start (data cut-off 20 May 2022). Methods Between 27 October 2015 and 16 May 2017, 135 previously untreated, medically fit patients with CLL were enrolled from 27 FILO centers. All received obinutuzumab 1000 mg (8 infusions over 6 cycles) plus ibrutinib (420 mg/day for 9 months). Following evaluation at D1 M9 (N=130 evaluable), those in CR with BM MRD <0.01% then continued only ibrutinib 420 mg/day for 6 additional months (I arm; n=10); otherwise, patients received 4 cycles of FC-obinutuzumab 1000 mg alongside continuing ibrutinib 420 mg/day for 6 additional months (I-FCG arm; n=115). Beyond end of treatment, patients were followed for peripheral blood (PB) MRD every 6 months, response every 3 months, progression-free/overall survival (PFS/OS), and safety. MRD was assessed by 8-color flow cytometry, using a highly sensitive (10-6) technique developed by the FILO group that enables subdivision of classical MRD <0.01% into low-level positive MRD <0.01% and undetectable MRD. Results At D1 M16, undetectable PB MRD rates were 80.0% (8/10) in the I arm and 92.5% (99/107) in the I-FCG arm. Beyond end of treatment, in the I arm the undetectable PB MRD rate decreased rapidly, and by M40 all patients had PB MRD positivity (≥0.01% or low-level positive <0.01%). In the I-FCG arm, the undetectable PB MRD rate was 76.3% (61/80) at M40, and of patients currently investigated at M64, 50/62 (80%) still had undetectable PB MRD (Figure 1). Four relapses occurred beyond end of treatment, including 2 CLL progressions (both Richter's syndrome). Throughout follow-up, no differences in undetectable PB MRD rates were apparent in the I-FCG arm according to the IGHV -mutated versus unmutated status (currently at M64: 20/27 versus 25/35, P=0.26). Overall 4-year PFS and OS rates (95% confidence intervals) were 95.5% (92% to 99 %) and 96.2% (93% to 99.5%), respectively. Of 12 deaths overall, 7 occurred beyond end of treatment, with 5 since last publication due to Richter's syndrome at M50, COVID at M50, lung cancer at M50, myelodysplastic syndrome at M60, and acute myeloid leukemia at M69. Other serious adverse events since last publication were metastatic prostate adenocarcinoma at M50 and suspicion of cerebrovascular accident at M65. Conclusion Long-term results from the ICLL-07 trial in previously untreated, medically fit patients with CLL demonstrated that that our fixed-duration (15-month) immunochemotherapy approach produced deep and sustained undetectable PB MRD responses that were correlated to PFS, without excess toxicity. These long-term MRD results remain the best to date even compared to the new targeted therapy combinations ie ibrutinib +veneteclax or obinutuzumab + venetoclax A randomized trial is needed to compare our approach with a chemotherapy-free strategy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hepar-1 Positive Prostatic Adenocarcinoma: A Case Report and Review of Literature

Abstract Introduction/Objective Poorly differentiated metastatic malignancy in patients with a history of more than one known primary tumor, such as a history of both hepatocellular and prostatic carcinoma as seen in our case, can be challenging. Both tumors are CK7/CK20 positive, and both can be reactive for hepar-1, as has been demonstrated in the current case, and rarely described in the literature. Methods/Case Report Herein we present a sixty-three-year-old male who presented for follow-up of his lower back pain in the setting of hepatocellular carcinoma. MRI of the spine was suggestive of an expansile metastatic lesion in the C2 vertebral body with extraosseous soft tissue extension resulting in moderate to severe central canal and left foraminal narrowing at C2-3. Multiple additional metastatic lesions were visualized throughout the cervical upper thoracic spine as detailed above. Vertebral body biopsy showed metastatic adenocarcinoma with sheets of neoplastic cells infiltrating the medullary spaces. The patient’s history of hepatocellular carcinoma was noted, and immunohistochemical staining for HepPar1 with appropriate control was performed and found to be diffusely reactive in the tumor cells. However, tumor cells were also positive for PSA, PSAP, and NKX3.1 (Fig-1-A-D, H&amp;E, Hepar-1, PSAP, PAP). This immunoprofile is consistent with a prostatic origin of the tumor cells, and a diagnosis of metastatic prostatic adenocarcinoma was given. Results (if a Case Study enter NA) NA. Conclusion Hepar-1 and even arginase-1 have been observed in rare subsets of prostatic acinar adenocarcinoma. Even in the setting of PSA and PSAP negative metastatic disease in patients with a history of hepatocellular carcinoma, we suggest utilizing additional stains suggestive of a prostatic origin, such as NKX3.1, and even molecular studies. This could be useful diagnostic approach to help differentiate between the two neoplasms in such patients.

PMON108 Metastatic Prostate Cancer Presenting as a Pituitary Macroadenoma: A Case Report

Abstract Introduction Prostate cancer is the most common non-skin malignancy with an increasing incidence of distant stage spread. Prostate cancer is most frequently associated with skeletal, lymph node, and pulmonary metastases. Intracranial metastases are rare, occurring in only 0.4-0.6 percent of all cases. However, silent pituitary metastases are not uncommon in autopsy reports of cancer patients, with breast and lung cancer being the most common primary origin. Here we report a rare case of metastatic prostate adenocarcinoma that was originally thought to be a pituitary macroadenoma. Clinical Case A 57-year-old male with no known history of malignancy who presented with two weeks of headaches exacerbated by leaning forward. MRI showed a 2.8×2.8×2.7 cm sellar/suprasellar mass extending into the clivus and right sphenoid sinus favored to reflect a pituitary macroadenoma. He was found to have no visual, neurological, or endocrine abnormalities on exam, in addition to normal laboratory evaluation. He subsequently underwent transnasal resection of the mass and pathology revealed metastatic prostate cancer. Postoperative studies also revealed a significantly elevated prostate specific antigen (PSA) level of 383.8 ng/mL (normal range 0-4ng/mL) and a left posterolateral prostate mass extending into the left seminal vesicle, as well as multiple osseous metastases. In retrospect, he had been found to have an elevated PSA of 49.5 ng/mL five months prior which was thought to be secondary to infection but had not yet been repeated by his primary care provider. Fortunately, he had a favorable response to androgen deprivation therapy and Abiraterone/Prednisone. His PSA level decreased to &amp;lt;0.1 ng/mL and MRI showed complete resolution of the sellar/suprasellar mass while on androgen deprivation therapy. Discussion The rarity of pituitary metastases as well as lack of specific clinical and radiological features can make it difficult to differentiate from the much more common benign pituitary adenoma. Pituitary metastases are frequently asymptomatic or can present similarly to pituitary adenomas with headaches, visual changes, or hypopituitarism. Posterior pituitary metastases have been more frequently reported than anterior, thought to be due to the larger area of contact with the adjacent dura and direct blood flow from the systemic circulation. Rapid progression of size and symptoms, age greater than 50, and presence of diabetes insipidus should all raise suspicion for pituitary metastases, regardless of oncologic history, as the differentiation between malignant and benign is imperative in determining a therapeutic plan. The overall prognosis is poor in patients with prostate cancer metastatic to the brain, with a reported mean survival of 1-3 months in untreated cases and up to 14 months in those who underwent surgery or radiotherapy. Conclusion This case reminds us of the importance of keeping malignant metastases in the differential diagnosis of sellar masses. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Metastatic prostate adenocarcinoma with neuroendocrine differentiation on 18F-FDG PET/CT, 68Ga-PSMA PET/CT and 68Ga-DOTA TATE PET/CT with injected ultra-low-activity

We report the case of a 69-year-old man with prostate cancer (PC), retroperitoneal lymph node metastases, and bone metastases, who received hormone therapy to date. The patient underwent a puncture biopsy in the third thoracic vertebra and was diagnosed with metastatic prostatic acinar adenocarcinoma with partly neuroendocrine differentiation. The patient underwent three different total-body PET/CT scans at ultra-low activities to evaluate tumor heterogeneity by multiple tracers (68Ga-PSMA PET/CT, 18F-FDG PET/CT, 68Ga-DOTA TATE PET/CT). Our case suggests that total-body PET imaging with 194-cm axial FOV using a 10×reduction in injected activity can yield images that meet diagnostic needs and that the results of multi-tracer analysis are encouraging for revealing the characteristics of each lesion.

A CASE OF PULMONARY TUMOR THROMBOEMBOLIC MICROANGIOPATHY FROM PROSTATE CARCINOMA

A CASE OF PULMONARY TUMOR THROMBOEMBOLIC MICROANGIOPATHY FROM PROSTATE CARCINOMA

S1986 Atypical Presentation of Metastatic Prostatic Adenocarcinoma as Large Bowel Obstruction

S1986 Atypical Presentation of Metastatic Prostatic Adenocarcinoma as Large Bowel Obstruction

FAMILY MATTERS: CHEST PAIN AS THE INITIAL PRESENTATION OF EARLY-ONSET METASTATIC PROSTATE CANCER

FAMILY MATTERS: CHEST PAIN AS THE INITIAL PRESENTATION OF EARLY-ONSET METASTATIC PROSTATE CANCER