Metastatic Prostate Adenocarcinoma Research Articles

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 <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

METASTATIC PROSTATIC ADENOCARCINOMA IN THE ORAL CAVITY: CASE REPORT

Metastasis to the oral cavity represents a challenging diagnosis, because it often clinically mimics reactive hyperplastic lesions and even primary malignancies. About 90% of cancer-related deaths are direct outcomes of metastatic disease. This study reports a clinical case of a 72-year-old male with a 3.5-cm asymptomatic nodule on the hard palate with unknown duration. The patient's medical records included a prostatic adenocarcinoma diagnosed 4 years before, treated with radiotherapy. No radiographic alterations were detected. Differential diagnosis included malignant tumors of salivary glands or metastasis from prostate cancer. An incisional biopsy was performed and the specimen was sent to histopathologic analysis. The final diagnosis was metastatic prostatic adenocarcinoma. The patient did not return for his results and died 3 weeks later. Despite being considered a rare event, metastasis to the oral cavity must be included in the differential diagnosis, especially for patients with a history of cancer. Metastasis to the oral cavity represents a challenging diagnosis, because it often clinically mimics reactive hyperplastic lesions and even primary malignancies. About 90% of cancer-related deaths are direct outcomes of metastatic disease. This study reports a clinical case of a 72-year-old male with a 3.5-cm asymptomatic nodule on the hard palate with unknown duration. The patient's medical records included a prostatic adenocarcinoma diagnosed 4 years before, treated with radiotherapy. No radiographic alterations were detected. Differential diagnosis included malignant tumors of salivary glands or metastasis from prostate cancer. An incisional biopsy was performed and the specimen was sent to histopathologic analysis. The final diagnosis was metastatic prostatic adenocarcinoma. The patient did not return for his results and died 3 weeks later. Despite being considered a rare event, metastasis to the oral cavity must be included in the differential diagnosis, especially for patients with a history of cancer.

Molecular and pathological subtypes related to prostate cancer disparities and disease outcomes in African American and European American patients.

Prostate cancer (PCa) disproportionately affects African American (AA) men, yet present biomarkers do not address the observed racial disparity. The objective of this study was to identify biomarkers with potential benefits to AA PCa patients. Differentially expressed genes (DEG) analysis coupled with gene set enrichment analysis (GSEA) and leading-edge genes analysis showed that the keratin family of genes, including KRT8, KRT15, KRT19, KRT34, and KRT80, constituted the single most prominent family of genes enriched in AA compared to European American (EA) PCa cell lines. In PCa patients (TCGA and MSKCC patient cohorts), KRT8, KRT15, and KRT19 expression were relatively higher in AA than in EA patients. The differences in the expression of KRT15 and KRT19, but not KRT8, were enhanced by Gleason score and ERG fusion status; in low Gleason (Gleason ≤ 6 [TCGA cohort] and Gleason ≤ 7 [MSKCC cohort]), the expression of KRT15 and KRT19 was significantly (p ≤ 0.05) higher in AA than in EA patients. Survival analysis revealed that high expression of KRT15 and KRT19 was associated with increased risk of biochemical recurrence in low Gleason category patients in the TCGA patient cohort. Interestingly, KRT15 and KRT19 expression were also associated with an increased risk of death in the metastatic prostate adenocarcinoma cohort, suggesting the potential to predict the risks of disease recurrence and death in the low Gleason category and advanced disease conditions respectively. Gene set enrichment analysis revealed known oncogenic gene signatures, including KRAS and ERBB2, to be enriched in patients expressing high KRT15 and KRT19. Furthermore, high KRT15 and KRT19 were linked to the basal and LumA PCa subtypes, which are associated with poor postoperative androgen deprivation therapy (ADT) response compared to the LumB subtype. Taken together, the present study identifies genes with high expression in AA than in EA PCa. The identified genes are linked to oncogenic gene signatures, including KRAS and ERBB2, and to basal and LumA PCa subtypes that are associated with poor postoperative ADT response. This study, therefore, reveals biomarkers with the potential to address biomarker bias in PCa risk stratification and/or prognosis.

Abstract 510: Molecular subtypes related to prostate cancer disparities and disease outcome in African American and European American patients

Abstract Prostate cancer disproportionately affects African American (AAM) men, yet present biomarkers do not factor in prostate cancer racial disparity. The objective of this study was to identify biomarkers with potential benefits to AAM prostate cancer patients. Differentially expressed genes (DEG) analysis coupled with gene set enrichment analysis (GSEA) and leading-edge genes analysis showed that the keratin family of genes, including KRT8, KRT15, KRT19, KRT34, and KRT80, constituted the single most prominent family of genes enriched in AAM compared to European American (EAM) prostate cancer cell lines. In prostate cancer patients (TCGA and MSKCC patient cohorts), only KRT8, KRT15, and KRT19 expression were relatively higher in AAM than in EAM. The differences in the expression of KRT15 and KRT19, but not KRT8, were enhanced by Gleason score and ERG fusion status; in low Gleason (Gleason ≤ 6 [TCGA cohort] and Gleason ≤ 7 [MSKCC cohort]), the expression of KRT15 and KRT19 was significantly (p ≤ 0.05) higher in AAM than in EAM patients. Survival analysis revealed that high expression of KRT15 and KRT19 was associated with increased risk of biochemical recurrence in low Gleason category patients in the TCGA patient cohort. Interestingly, KRT15 and KRT19 expression was associated with an increased risk of death in the metastatic prostate adenocarcinoma (SU2C/PCF Dream Team, PNAS 2019) cohort, suggesting the potential to predict the risks of disease recurrence and death in the low Gleason category and advanced disease conditions respectively. Gene set enrichment analysis revealed known oncogenic gene signatures, including KRAS and ERBB2, to be enriched in patients expressing high KRT15 and KRT19. Furthermore, high KRT15 and KRT19 were linked to the basal and LumA prostate cancer subtypes associated with poor postoperative androgen deprivation therapy (ADT) response compared to the LumB subtype. Taken together, the present study identifies genes with high expression in AAM than in EAM prostate cancer. The identified genes are linked to oncogenic gene signatures, including KRAS and ERBB2, and to basal and LumA prostate cancer subtypes that are associated with poor postoperative ADT response. The study, therefore, reveals biomarkers with the potential to address biomarker bias in prostate cancer diagnosis and/or prognosis. Future studies would explore the diagnostic and/or prognostic potential of identified markers in prostate cancer tissue samples. Citation Format: Joakin Opeli Mori, Jason White, Balasubramanyam Karanam, Clayton Yates, Honghe Wang. Molecular subtypes related to prostate cancer disparities and disease outcome in African American and European American patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 510.

Abstract 653: Molecular pathology of metastatic prostatic adenocarcinoma treated with bipolar androgen therapy (BAT) reveals a correlation between MYC mRNA and protein

Abstract Molecular analysis of tissue samples from metastatic cancer lesions can improve our understanding of drug response and resistance. Since prostate cancer cells initially require androgen signaling through the androgen receptor (AR) for proliferation, the treatment of metastatic prostate cancer involves surgical or chemical castration. While most patients respond initially, nearly all develop acquired resistance to combined androgen blockade using both first and second line agents. This resistance is often related to overexpression of AR, which is frequently driven by AR gene amplification. In some patients, this increased AR appears to render tumor cells sensitive to high dose androgens in a manner that paradoxically inhibits their growth. Bipolar Androgen Therapy (BAT) was introduced several years ago at our institution in which patients with castration resistant prostate cancer (CRPC) are treated intermittently with high dose testosterone. Prior clinical trials have shown that BAT can produce biochemical and objective responses, and may re-sensitize prostate cancer to subsequent second generation AR inhibitors. To define the mechanism(s) by which BAT results in tumor regression, we performed a clinical trial (NCT03554317) for patients with CRPC that included biopsies of soft tissue metastases before BAT and after 3 cycles of BAT (C4D1). Up to four tissue cores were taken per biopsy with two cores for formalin fixation and paraffin embedding (FFPE) and the others snap frozen. Histologically viable tumor cells were present for both the pretreatment and C4D1 time points for 24 of the 42 enrolled patients. The FFPE samples were stained for H&E and by IHC for AR, MYC and Ki67. MYC and Ki67 IHC stained slides were subjected to quantitative image analysis using HALO software (Indica Labs). Adequate frozen tumor tissue was available for laser capture microdissection and adequate amounts of RNA were obtained from 15 patients with paired pretreatment and C4D1 biopsies. RNAseq libraries were prepared using the NuGEN Ovation RNA-Seq System V2 and barcoded libraries were sequenced to an average depth of > 100 million reads per sample on an Illumina NovaSeq. Gene expression values were obtained with RSEM using Star aligner with GRCh38 (human). When comparing the C4D1 samples to the pretreatment samples, there were marked decreases in tumor MYC protein levels in approximately half of the treated patients, which was associated with decreased Ki67, decreased tumor volume, and prolonged progression-free survival on BAT. Using an image analysis computed H-SCORE for MYC, there was a strong correlation between MYC protein levels and MYC mRNA using RNAseq (r=0.81, p = 2.3 x 10-7). This indicates that MYC protein levels correlate with MYC mRNA and that reductions of MYC protein by BAT are likely related to reductions of MYC mRNA in clinical metastatic tissue samples. Citation Format: Carolina Gomes Alexandre, Tracy Jones, Jessica L. Hicks, John T. Isaacs, Anuj Gupta, Alyza Skaist, Laura Sena, Jennifer Meyers, Emmanuel Antonarakis, Mark Markowski, Samuel Denmeade, Srinivasan Yegnasubramanian, Angelo Michael De Marzo. Molecular pathology of metastatic prostatic adenocarcinoma treated with bipolar androgen therapy (BAT) reveals a correlation between MYC mRNA and protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 653.

Purple urine bag syndrome: a perplexing finding in a urethral catheter related urinary tract infection

The appearance of purple coloured urine within the Urethral Catheter-Urine Bag system is often frightening to patients and their relatives and gets health care givers perplexed. The purple colour is said to be a by-product of chemical transformation of indole to indigo or indirubin, or a mixture of the two. Both Indigo and Indirubin are derivatives of colonic bacterial metabolism of dietary Tryptophan using either the Sulphatase or Phosphate enzymes or both. It is seen in chronically ill patients with chronic constipation and on long standing urethral catheterisation. The organisms commonly cultured from such purplish urine are Escherichia coli, proteus mirabilis, klebsiella pneumoniae and Enterobacter species. We reported such a case in a 98-year old paraplegic male patient with a histologically proven metastatic prostate adenocarcinoma and chronic constipation. The urine and catheter tip culture yielded klebsiella specie. We wrote to draw attention to its occurrence and highlight a simple method of its treatment.

Ocular complications with the use of radium-223: a case series

BackgroundRadium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient’s second course of radium-223.Case presentationsWe present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema.ConclusionsDocumentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation’s potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.

An unusual presentation of metastatic prostatic adenocarcinoma: a case report

An unusual presentation of metastatic prostatic adenocarcinoma: a case report

Neurocryptococcosis and leptomeningeal carcinomatosis in metastatic prostate adenocarcinoma: differential diagnoses or overlapping symptoms?

Acute headaches with red flags in patients with cancer may indicate metastasis or infection. This report describes a case of acute headache with red flags in a patient with metastatic prostate adenocarcinoma who presented a positive latex fixation test without pleocytosis in cerebrospinal fluid (CSF) analysis. Antifungal treatment was initiated based on the test's high accuracy combined with the patient’s clinical condition and radiological impression of infectious meningitis, although we could not exclude associated secondary neoplastic involvement. Clinical improvement was first observed on D4 of treatment. On D14, CSF examination revealed therapeutic efficacy but positive oncotic cytology. The patient subsequently had new episodes of headache with warning signs and magnetic resonance imaging showed leptomeningeal carcinomatosis. Although neurocryptococcosis and leptomeningeal carcinomatosis are rare neurological complications, they may coexist with overlapping symptoms.

68Ga-PSMA-11 PET/CT Initial Staging in Black and White South African Males with ISUP Grade Group 1 and 2 Prostate Adenocarcinoma.

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design

Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. Janssen-Cilag, Ipsen, Sanofi, and the French Government.

Detecting Neuroendocrine Prostate Cancer Through Tissue-Informed Cell-Free DNA Methylation Analysis.

Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to noninvasively detect NEPC. We first performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors, identified differentially methylated regions between NEPC and CR-PRAD, and built a model to predict the presence of NEPC (termed NEPC Risk Score). We then performed MeDIP-seq on cell-free DNA (cfDNA) from two independent cohorts of men with NEPC or CR-PRAD and assessed the accuracy of the model to predict the presence NEPC. The test cohort comprised cfDNA samples from 48 men, 9 with NEPC and 39 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 4.3 × 10-7) and discriminated between NEPC and CR-PRAD with high accuracy (AUROC 0.96). The optimal NEPC Risk Score cutoff demonstrated 100% sensitivity and 90% specificity for detecting NEPC. The independent, multi-institutional validation cohort included cfDNA from 53 men, including 12 with NEPC and 41 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 7.5×10-12) and perfectly discriminated NEPC from CR-PRAD (AUROC 1.0). Applying the predefined NEPC Risk Score cutoff to the validation cohort resulted in 100% sensitivity and 95% specificity for detecting NEPC. Tissue-informed cfDNA methylation analysis is a promising approach for noninvasive detection of NEPC in men with advanced prostate cancer.

A phase 1b clinical trial of cabozantinib (CABO) and abiraterone (ABI) with checkpoint inhibitor immunotherapy (CPI) in metastatic hormone-sensitive prostate cancer (mHSPC) (CABIOS Trial).

TPS214 Background: Multiple systemic therapies have resulted in improved overall survival (OS) for mHSPC, including several AR-targeted agents (ARTA) and docetaxel chemotherapy. However, patients (pts) with high volume de novo metastatic prostate cancer still only have an OS of approximately 50 months. Thus, more effective combination strategies for initial treatment of mHSPC are urgently needed. CABO, a multi-tyrosine kinase inhibitor (including MET, VEGFR-1, -2,-3, AXL) has shown synergy with ABI as well as with CPI in preclinical studies. CABO and ABI have demonstrated an acceptable safety profile in metastatic castration resistant prostate cancer (mCRPC) (Choudhury et al Prostate 2018), and CABO and atezolizumab (ATEZO) in combination have showed a promising efficacy signal and manageable safety profile in mCRPC (COSMIC-021, NCT03170960; Agarwal ESMO 2021). The phase 3 CONTACT-02 trial (NCT04446117) is randomizing mCRPC pts to either CABO and ATEZO or a second generation ARTA. Given the robust preclinical and emerging clinical data for the use of both CABO and CPI therapy in advanced prostate cancer and the need to optimize therapy earlier in the course of disease, in the present trial we intend to evaluate the safety and tolerability of ABI, CABO, and CPI in mHSPC. Methods: CABIOS (NCT04477512) is a phase Ib, single center, open label trial of ABI, CABO and the CPI nivolumab (NIVO), an anti-PD-1 monoclonal antibody, in pts with mHSPC. Key inclusion criteria include histologically or cytologically confirmed metastatic prostate adenocarcinoma without neuroendocrine/small cell differentiation and radiographic evidence of metastatic disease. Ongoing androgen deprivation (ADT) within 12 weeks of study start is allowed. Key exclusion criteria include evidence of castration resistance, prior treatment with second-generation androgen receptor inhibitors, CYP17 inhibitors, CABO, or checkpoint inhibitor immunotherapy (anti-PD-1/PD-L1, CTLA-4), active autoimmune disease, and ongoing treatment with systemic corticosteroids daily. The primary objective of the trial is evaluation of the safety and tolerability of this combination therapy in the trial population; the primary endpoint is the frequency of dose-limiting toxicities (DLTs) as measured by CTCAE v5.0. The study will employ a 3 + 3 design evaluating ABI 1,000 mg once daily with prednisone 5 mg daily, NIVO 480 mg IV every 4 weeks, and a CABO starting dose of 20 mg once daily at dose level 1 (DL1). If 0 of 3 pts at DL1 experience a DLT, 3 pts will be enrolled at DL2 with CABO 40 mg once daily. If 1 of 3 pts at DL1 experience a DLT, 3 additional pts will be enrolled at DL1. If 0 of 3 pts experience a DLT at DL2, the study will move to a recommended phase 2 dose (RP2D) expansion cohort. Total sample size of approximately 20 pts is expected depending on DLT frequencies. Enrollment is ongoing. Clinical trial information: NCT04477512.

Risk Stratification of Prostatic Adenocarcinoma Metastatic to the Lymph Nodes.

The pathologic nodal staging of prostatic adenocarcinoma is binary for regional lymph nodes. Stages pN0 and pN1 indicate the absence or presence of regional nodal metastasis, respectively, whereas patients with metastasis to nonregional lymph nodes are staged as pM1a. To determine the risk of recurrence of pN1 prostatic adenocarcinoma patients based on the extent of nodal tumor burden. We retrospectively reviewed pN1 patients with prostatic adenocarcinoma managed with radical prostatectomy seen between 2011 and 2019. Kaplan-Meier and Cox regression analyses were performed to compare disease-free survival. Ninety-six patients were included (median [interquartile range] age, 62 years [57-67 years]; 70 of 96 [73%] White). On univariate analysis, age >65 years (P = .008), ≥2 positive regional lymph nodes (P < .001), and a maximum size of the tumor deposit ≥2 mm (P = .004) were significantly associated with an unfavorable outcome. Controlling for age, stage, metastatic deposit size, margin status, and the presence of extranodal extension, patients with ≥2 positive regional lymph nodes were 3.03 times more likely (95% confidence interval, 1.39-6.60; P = .005) to have an unfavorable outcome. Patients with pN1M1a stage showed a disease-free survival similar to that of pN1M0 patients, after controlling for the number of positive regional lymph nodes (P = .36). Overall, pN1 patients with ≥2 positive regional lymph nodes are 3 times more likely to have an unfavorable outcome. The results suggest a benefit in further stratifying patients with metastatic prostatic adenocarcinoma to the lymph nodes into prognostically significant risk categories that could help the treating clinicians tailor subsequent patient follow-up and therapy.

Assessment of Utility of Immunohistochemical Marker Prostein for Evaluation of Primary and Metastatic Prostatic Carcinomas

Background: To assess utility of immunohistochemical marker prostein for evaluation of primary and metastatic prostatic carcinomas.Methods:Fifty- six samples of clinically suspected carcinoma prostate was included. Immunohistochemistry (IHC) was performed for assessment of Prostein (P501S). The intensity of positivity was scored from 0 to 3 as follows: score 0 = non-stained; score 1 = weak; score 2 = moderate; and score 3 = strong. The percentage of positively stained cells for each staining intensity was estimated in the respective lesions.Results:Age group 18-28 years comprised of 6 patients, 28-38 years had 12, 38- 48 years had 16 and &gt;48 years had 22 cases. Type of cases were normal prostatic epithelium in 11, benign prostate hyperplasia in 23, HGPIN in 10, primary prostatic adenocarcinoma in 7 and metastatic prostatic adenocarcinoma in 5 cases. Prostein expression was seen in 100% in normal prostatic epithelium with intensity score of 1.8-2.1, benign prostate hyperplasia having 2-2.7, HGPIN with 2-2.3, primary prostatic adenocarcinoma having 1-1.6 and metastatic prostatic adenocarcinoma with 0.8-1.4 intensity score. Conclusion:Prostein is a new prostate specific marker which showed 100% sensitivity and specificity to identify normal and prostatic lesions.

Facility-Level Variation in Use of Locoregional Therapy for Metastatic Prostate Cancer.

We sought to understand patient- and institution-level factors associated with use of locoregional therapy for newly diagnosed metastatic prostate cancer in the era before the availability of evidence supporting its efficacy. We queried the National Cancer Database to identify patients diagnosed with metastatic prostate adenocarcinoma (stage M1) between 2004 and 2017. We assessed patient factors associated with definitive local therapy with radiotherapy or radical prostatectomy using multilevel logistic regression accounting for clustering within institutions. We further characterized trends in facility-level use and examined institutional factors associated with utilization. We identified 35,933 patients with M1 prostate cancer at 1,188 facilities. A total of 4,146 patients (11.5%) received local therapy for M1 disease (radiation therapy in 3,378 and radical prostatectomy in 768). Use of local treatment was concentrated among a smaller number of facilities: 50% of all local therapy was delivered at 161 facilities (14% of total). At the patient level, uninsured status (OR 0.62, 95% CI 0.49-0.79, p <0.01) and high comorbidity (Charlson-Deyo score, OR 0.39, 95% CI 0.26-0.6, p <0.01) were associated with lower odds of local therapy. High-utilizing facilities (top quartile) were more commonly community centers (OR 1.76, 95% CI 10.7-2.95, p <0.01) and differed by geographic region (South Atlantic vs West South Central region: OR 0.48, 95% CI 0.25-0.88, p=0.02). In the period before locoregional therapy was supported by clinical practice guidelines, locoregional therapy use varied significantly at the facility level and was driven by a smaller number of high-utilizing facilities. These findings can contextualize expected increase in the use of local therapy for metastatic prostate cancer.