Detection Of High-risk Prostate Cancer Research Articles

The Value of SUVmax of Gallium-68-PSMA PET/CT in Newly Diagnosed Prostate Cancer

OBJECTIVES: To evaluate the correlation between the intensity of prostate specific membrane antigen (PSMA) expression by Gallium-68-PSMA positron emission tomography/computer tomography (Ga-68-PSMA PET/ CT) and the D’Amico risk classification of newly diagnosed prostate cancer patients. MATERIALS AND METHODS: Retrospective reviews of 61 newly diagnosed prostate cancer patients, who underwent Ga-68-PSMA PET/CT between September 2017 and November 2021. Data of maximum standard uptake value (SUV max) of prostate tissue was collected. The correlation between SUV maximum value and D’Amico risk classification, as well as Gleason score (GS) grade group and prostate specific antigen (PSA) level, was evaluated. For the data analysis, the Kruskal-Wallis test, Pearson correlation, and receiver operating characteristic curve (ROC curve) analysis were carried out. RESULTS: Most of the patients (50 patients, 82%) were in the high risk D’Amico risk classification. The mean SUVmax values of the primary tumor for all patients were 15.7 ± 10.5. The SUVmax values for low and intermediate-risk patients (9.5 ± 4.76) were significantly lower than those of high-risk patients (17.06 ± 10.93) (p-value 0.013). A positive correlation was found between SUVmax values and the GS grade group (p-value 0.025), while there was a low correlation between PSA level and SUVmax values. The cutoff SUVmax value of 8.3 showed a sensitivity (84%) and specificity (63.6%) for the detection of high-risk prostate cancer. CONCLUSION: PSMA expression in primary tumors is significantly higher in patients with higher GS grade groups and high-risk D’Amico staging, but it is not correlated with PSA level. Ga-68-PSMA PET/CT can be used to screen high-risk prostate cancer patients and potentially help in an individualized treatment decision.

Abstract 3383: Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer

Abstract Prostate cancer is one of the most common cancers in men. The disease is largely indolent in nature and treatment of low-risk prostate cancer is not always necessary. However, a fraction of the patients will progress to aggressive disease which accounts for most of the cancer related mortality. Detection methods accurately differentiating between high- and low-risk patients for lethal prostate cancer is a critical need and currently, prostate biopsies and subsequent histopathology and molecular profiling are the most definitive way to differentiate between these two patient populations. But biopsies are invasive procedures associated with significant morbidity. Hence, there exists a critical need to develop non-invasive and highly sensitive diagnostic biomarkers to avoid unnecessary biopsies. Here, we propose to develop a novel biomarker panel which constitutes of a class of RNA molecules called circular RNA (circRNA) to be detected in liquid biopsies. Circular RNAs are covalently closed RNA structures, which are resistant to degradation by exoribonucleases because of the absence of free termini in their nucleotide chain. Due to their increased stability compared to their linear counterparts, circRNAs are ideal candidates for biomarkers, especially in non-invasive liquid biopsies. Using MiOncoCirc, a circRNA compendium from >2,000 primary and metastatic cancer tissues representing 40 cancer types, we first identified 9 circRNAs that are specifically expressed in prostate adenocarcinoma (PRAD) compared to all other cancer types. Next, we examined if these candidates are differentially expressed between PRAD and normal prostate tissues. Based on higher levels of expression which were statistically significant in the PRAD compared to normal prostate tissues, we promoted 4 circRNAs to our biomarker panel. In addition, our panel also includes 2 circRNAs that we predicted to arise from PRAD specific lncRNAs. To study the expression of the novel 6-circRNA biomarker expression in high-risk prostate cancer patients we developed a capture-based RNA sequencing assay. For the initial round we used this assay to test our pilot post-DRE patient urine sample EDRN cohort and detected expression of the prostate cancer-specific circRNAs in a subset of these post-DRE urine samples. We are in the process of expanding our test cohort which will also contain additional clinical annotations such as Gleason score. Post cohort assembly we intend to run our 6-circRNA capture assay on these samples to determine whether the expression levels of candidate circRNAs are correlated with disease stage and other clinical parameters. Our results will facilitate the rapid development of a diagnostic test using non-invasive urine samples for the early detection of high-risk prostate cancer. Citation Format: Palak Shah, Pushpinder Bawa, Lanbo Xiao, Yelena Kleyman, Josh Vo, Saravana M. Dhanasekaran, Jason Brown, Nicolette Loeding, Alexander Koons, Javed Siddiqui, Xuhong Cao, Arul M. Chinnaiyan. Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer [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 3383.

Urinary biomarkers of prostate cancer.

The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

A positive real‐time elastography is an independent marker for detection of high‐risk prostate cancers in the primary biopsy setting

To evaluate the performance of real-time elastography (RTE) in an initial biopsy setting. In the period from February 2011 to June 2012, 127 consecutive patients were included in the study. We used a Hitachi Preirus with Hi-RTE module, a prostate end-fire transrectal probe was used for RTE and for targeted biopsies, and a simultaneous biplane probe was used for the standard systematic biopsies. The peripheral zone of the prostate was divided into six regions, and each biopsy obtained was referred to a specific region. All patients were first examined with RTE and, if cancer was suspected, targeted biopsies were taken. A standard systematic 10-core biopsy was then taken in all patients. In all, 64 (50%) patients were diagnosed with prostate cancer in the initial biopsy setting. Three patients were diagnosed solely on RTE-targeted biopsies, 31 were found only in systematic biopsies, and 30 were correctly diagnosed with both methods. In the RTE-positive group there was a significantly higher frequency of positive cores, a lower prostate volume, a higher Gleason score, and a higher fraction of cancer tissue in each core. In a multiple regression model RTE was an independent marker for high-risk cancer. The sensitivity of 42% for all prostate cancers increased to 60% for high-grade prostate cancers. Similarly, the negative predictive value increased from 79% to 97%. An additional eight patients were diagnosed with prostate cancer during the study period. A positive RTE is an independent marker for detection of high-risk prostate cancer, and a negative RTE argues against such. RTE with targeted biopsies cannot replace systematic biopsies, but provides valuable additional information about the tumours.

New experimental markers for early detection of high-risk prostate cancer: role of cell–cell adhesion and cell migration

Today's treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual field of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively. For therapeutic interventions it is important to distinguish between harmless and aggressive disease in an early stage. Therefore the subject of this review is limited to markers associated with those functional processes, which discriminate early stage aggressive, metastatic cancer from harmless disease. Important processes in this respect are: altered cell adhesion and cellular migration. E-cadherin, N-cadherin, beta-catenin, integrins, focal adhesion kinase, connexins and matrix metalloproteinases all appear promising biological markers associated with the early stage metastatic process in prostate cancer. Here we discuss their potential to become valid biological markers based on literature data. Thus far, none of these markers proved to be a valid individual marker by itself due to prostate cancer heterogeneity and transient expression. Analyzing a combination of the potential markers discussed in this review is expected to be a better approach toward discriminating high- from low-risk tumors in an early stage of prostate cancer.