Maryland Archives

Urologic Perspective on the Current and Emerging Role of Multi-Modality Imaging and Radiogenomics

Posted by Mohummad Minhaj Siddiqui, MD | Feb 2022

Mohummad Minhaj Siddiqui, MD, Associate Professor of Surgery at the University of Maryland School of Medicine and Chief of Urology at the Baltimore VA Medical Center in Redwood, Maryland, discusses the role of precision imaging and genomics in managing localized prostate cancer. He first considers how treatment strategies will vary based on cancer aggressiveness, ranging from active surveillance in low-risk cancer to multimodal treatment in advanced and metastatic cancer. Dr. Siddiqui cites the PROMIS study which stratified risk of significant cancer based on MRI suspicion score of lesions. He points out that even at that high end of the scale, MRI identified cancers in some patients that either had insignificant or no cancer, demonstrating that imaging cannot replace biopsy. Equally important, at the low end of the scale, half of patients have cancer not shown in the scan. Dr. Siddiqui adds that while a scan may not suggest high-risk cancer, this is not the same as not having cancer. He then discusses the growth of genomic profiling in understanding genomic characteristics of prostate cancer. Genomic profiling is available for different stages of prostate cancer workup from susceptibility characterization to disease risk stratification and prediction of treatment response. The GC score in genomic characterization has similar limitations as imaging, leading to the question of whether these two modalities are capturing the same underlying issue or complementing each other. Dr. Siddiqui then describes how he uses imaging in a surgical setting for margin size and extracapsular extension at radical prostatectomy. He concludes that while it is not perfect, advanced imaging can improve risk stratification and assist with cancer staging and treatment planning. Similarly, genomics can also improve risk stratification and can reduce interventions like adjuvant radiation.

Emerging Role of PSMA Imaging

Posted by Steven P. Rowe, MD, PhD | Dec 2021

Steven P. Rowe, MD, PhD, Associate Professor of Radiology and Radiological Science at Johns Hopkins University in Baltimore, Maryland, discusses the emerging role of prostate-specific membrane antigen (PSMA) imaging. He defines PSMA as a transmembrane carboxypeptidase highly expressed in prostate cancer cells. This expression has been observed in over 95 percent of prostate cancer tumors, with a direct correlation between expression levels and tumor aggressiveness. Due to this, Dr. Rowe asserts that PSMA is an excellent target for molecular imaging of prostate cancer. Dr. Rowe displays a PSMA structure and activity diagram and explains that PSMA positron emission tomography (PET) has moderate sensitivity and very high specificity for pre-operative nodal staging, high detection efficiency for sites of biochemical recurrence (BCR), and can effectively guide focal therapy for oligometastases and is effective in selecting patients for endoradiotherapy. He then discusses each of these in more detail, highlighting data from a study that evaluated the diagnostic performance of PSMA-targeted 18F-DCFPyL PET/computerized tomography in the preoperative staging of men at high risk for harboring metastatic prostate cancer. Dr. Rowe shows data on PSMA-based therapy and points out that for patients with more widespread metastatic disease, treatment may include PSMA inhibitors such as lutetium-177. Dr. Rowe expects that lutetium-based PSMA therapy will be approved by the FDA and become part of the standard of care for patients with widespread metastatic disease. Dr. Rowe then outlines lingering questions about PSMA PET imaging, including how prognostic findings may look for different patient populations, how doctors should follow response to therapy given that decreasing androgen signaling leads to increase in PSMA expression, and what role artificial intelligence (AI) is going to play. Dr. Rowe illustrates data from the Observation vs. Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) trial results for oligometastatic disease, pointing out that patients who had all lesions visible on a PSMA scan treated had better outcomes than those who only had a subset of their PSMA-positive lesions treated. Dr. Rowe predicts that in the near term, AI will provide lesion classification, whole-body tumor burden assessments, and prognostication and decision-making based on scan findings and clinical data. In conclusion, Dr. Rowe explains that, based on existing studies, there are already multiple indications for diagnostic PSMA-based imaging, with the caveat that researchers are just starting to understand PSMA-targeted PET findings as imaging biomarkers, and currently there are still questions about the interface of PSMA PET with AI.

The Microbiome as a Mediator of Prostate Carcinogenesis

Posted by Karen Sandell Sfanos, PhD | Aug 2021

Karen Sandell Sfanos, PhD, Associate Professor of Pathology, Oncology, and Urology at Johns Hopkins University, the Sidney Kimmel Comprehensive Cancer Center, and the Brady Urological Research Institute, presents and explains the results of a study conducted in her lab on the ability of bacterial infections to cause oncogenic TMPRSS2:ERG gene fusions. She begins by looking at proliferative inflammatory atrophy (PIA), which has been proposed as a risk factor that may play a key role in the development of prostate cancer (PCa). Dr. Sfanos then discusses two Science articles on the recurrent fusion of TMPRSS2 and ETS transcription factor genes in PCa and how Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Both of these articles discuss colibactin, which comes from E. coli and breaks DNA strands through DNA alkylation. Dr. Sfanos continues by analyzing a study on acute Escherichia coli prostatitis in previously healthy young men which found that over 70% of the E. coli isolate strains in patients with prostatitis contained the colibactin gene, leading directly to the hypothesis of her own study. She studied a series of cases that had active bacterial infections in the prostate at the time of prostatectomy, finding a high frequency of ERG expression in PIA lesions undescribed in scientific literature, that ERG positive PIA lesions are often found with early invasive micro adenocarcinoma, that colibactin producing bacteria were in the infected prostates, and that colibactin induces DSB at TMPRSS2 and ERG loci. Dr. Sfanos concludes that bacterial prostatitis should be considered as a risk factor for prostate carcinogenesis and that prostate infections may contribute to other oncogenic events. Dr. Sfanos then participates in a Q&A session featuring such topics as the protective potential of some of the isolates that may not be producing colibactin, research on inhibitors, and how urologists may use this information.

Freehand Transperineal Prostate Biopsy Under Local Anesthesia

Posted by Michael A. Gorin, MD | May 2021

Michael A. Gorin, MD, a urologist with Urology Associates of Cumberland, Maryland, explains the benefits of transperineal prostate biopsy compared to the transrectal approach for prostate cancer patients. First, he discusses the complications of transrectal biopsy, specifically infection risk, and demonstrates how the transperineal approach can decrease this risk without contributing to antibiotic resistance. He then explains how transperineal biopsy aids in improved detection and cancer upgrading. Dr. Gorin goes on to review transperineal biopsy methods, including the use of the Precisionpoint Transperineal access system. Finally, he summarizes block techniques and biopsy templates for freehand transperineal prostate biopsy under local anesthesia in the outpatient setting.

The TRANSFORMER Study: Bipolar Androgen Therapy vs. Enzalutamide in Asymptomatic Men With mCRPC

Posted by Samuel R. Denmeade, MD | May 2021

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at University of California, San Diego discusses the TRANSFORMER study and bipolar androgen therapy with Samuel R. Denmeade, MD, Professor of Oncology and Urology at Johns Hopkins University and co-leader of the Prostate Cancer Program for the Johns Hopkins Kimmel Cancer Center. Dr. Denmeade presents the study results, outlines the conceptual background, and notes the benefits of bipolar androgen therapy. TRANSFORMER compared enzalutamide with bipolar androgen therapy, a treatment in which testosterone levels are oscillated between low and high levels in order to prevent the adaptation of prostate cancer cells to a low-androgen environment. Results indicate that while bipolar androgen therapy may not have superior progression free survival rates when compared with enzalutamide, it can improve patient response to enzalutamide, suggesting that further research on sequential treatment is warranted. Notably, some men undergoing bipolar androgen therapy experienced a return in sexual function and also better physical functioning which contributed to improved quality of life.