Handoo Rhee

Adverse effects of androgen-deprivation therapy in prostate cancer and their management

To provide an up‐to‐date summary of current literature on the management of adverse effects of androgen‐deprivation therapy (ADT).

68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. EVIDENCE ACQUISITION Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. EVIDENCE SYNTHESIS Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. CONCLUSIONS 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.

Metabolic Syndrome and Prostate Cancer: a Review of Complex Interplay Amongst Various Endocrine Factors in the Pathophysiology and Progression of Prostate Cancer

The human prostate gland is an endocrine organ where dysregulation of various hormonal factors may play a pivotal role in the pathogenesis of prostate cancer. There is emerging epidemiological data to support the role of components of metabolic syndrome, namely, obesity, hypercholesterolaemia, diabetes and hyperinsulinaemia on the development and/or the progression of prostate cancer. Although the exact mechanisms behind the relationship between metabolic syndrome and prostate cancer remain largely unknown, various in vitro and animal experiments of metabolic syndrome models have been shown to promote survival, mitogenesis, metastasis and treatment resistance pathways, through various adaptive responses such as intracellular steroidogenesis and lipogenesis. Also, in a large proportion of men with metabolic syndrome, alteration in levels of hormones such as testosterone, leptin and adiponectin has been shown to contribute towards the aggression of prostate cancer. Whilst the exact bio-pathophysiological mechanisms between metabolic syndrome and prostate cancer are yet to be fully elucidated, medications that target specific components of metabolic syndrome have further provided evidence for the inter-relationship between metabolic syndrome, its components and prostate cancer. Emerging in vitro and molecular data is likely to bring us closer to utilizing this knowledge to target particular cancer survival pathways and improving outcomes for men with prostate cancer.

Using prostate specific membrane antigen (PSMA) expression in clear cell renal cell carcinoma for imaging advanced disease

Prostate specific membrane antigen (PSMA) is a 750 amino acid, type II transmembrane glycoprotein that has been shown to be over-expressed in both prostate cancer cells and the vasculature of solid tumours.1 Also known as folate dehydrolase, glutamate carboxypeptidase II or N-acetyl-L-aspartyl-L-glutamate peptidase I,2 PSMA has numerous metabolic roles and high levels of expression have been associated with tumour aggressiveness and malignant potential of prostate cancer cells...

Lower urinary tract imaging in pelvic fracture: an 11-year review of genitourinary complications and clinical outcomes

Diagnostic cysto‐urethrogram (CUG) is accepted as the standard of imaging for lower urinary tract (LUT) injuries in patients with pelvic fracture. This study evaluates the prevalence of LUT trauma and adequacy of diagnostic CUG in the initial assessment of patients with pelvic fractures.

Imaging tumour thrombus of clear cell renal cell carcinoma: FDG PET or PSMA PET? Direct in vivo comparison of two technologies

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal malignancy in adults.1 The disease is usually radiologically imaged with computed tomography (CT) or magnetic resonance imaging (MRI) for diagnosis, staging, treatment planning and follow up. Recently, functional studies targeting glucose or folate metabolism with fludeoxyglucose (FDG) or prostate specific membrane antigen (PSMA) binding ligands respectively have been reported to be used to stage the disease.2 Positron emission tomography (PET) using PSMA ligand detected larger number of lesions in comparison to conventional imaging modalities such as CT in a small prospective clinical trial.3 In this project, we directly compared the findings from FDG and PSMA PET in a patient with metastatic ccRCC. We assessed ex-vivo tumour characteristics to explain these findings.

Case Report: Spontaneous Hemorrhage of a Rare Renal Tumor in the Native Kidney of a Renal Transplant Recipient

Renal cancers are some of the most common solid organ malignancies found during follow-up of patients who have undergone renal transplantation (RT). In this case report, we describe a life-threatening spontaneous hemorrhage of a rare subtype of renal cell carcinoma in the native kidney of a 27-year-old man, 4 years after RT. After fluid resuscitation and stabilization, the patient underwent emergent open radical nephrectomy with the final histopathology reporting T1bN0Mx mucinous tubular and spindle cell (MTSC) carcinoma. This case report highlights the need to consider an underlying malignancy in patients who presents with spontaneous hemorrhage of native kidneys after RT.

MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA

planar scintigraphies was carried out by a twin head gamma camera (Siemens, ECAM and Symbia S) and indirect body contouring. Additionally, we subsequently performed SPECT/CT of the abdomen und inguinal regions using a twin-head hybrid camera system (Siemens Symbia T and Symbia Intevo). Imaging data of both modalities were prospectively evaluated by two experienced physicians in consensus reading in 52 groins of 26 patients with this tumor entity. RESULTS: A total of 71 SLNs in 37 groins were identified by planar scintigraphy. Non-visualization was observed in 15 (28.8%) inguinal basins using planar scans. 82 SLNs in 42 groins were detected by SPECT/CT (non-visualization in 10 (19.2%) groins). SPECT/CT revealed 8 inguinal hotspots as shown by planar imaging in 7 groins as false positive. 19 inguinal SLNs in 16 groins were missed on planar imaging and could be detected by SPECT/CT only. In contrast to 2D planar scintigraphy, SPECT/CT allowed to determine the precise anatomical localization of the SLNs in all 42 groins. CONCLUSIONS: SPECT/CT is capable of detecting SLNs missed by planar imaging, it reduces the number of false positive findings and shows the morphological location of SLNs more accurately. If available, SPECT/CT should be used for preoperative SLN imaging in penile cancer patients with non-palpable inguinal lymph node status.

PNFBA-08 NOVEL IN VITRO ORGANOID TECHNOLOGY TO FACILITATE A PRECISION MEDICINE APPROACH IN THE MANAGEMENT OF MEN WITH BIOCHEMICAL RECURRENCE OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Precision medicine aims to provide the right treatment for the right patient at the right time with treatment directed on the basis of the targetable tumoral aberrations rather than just a traditional histologic subtype. However to facilitate this approach, clinicians require patient derived samples. Prostate cancer is challenging to culture in vitro. Recent development of novel organoid in vitro culture technology has led to the development of multiple new in vitro prostate cancer cell line models. We aim to apply organoid culture technology to develop novel in vitro prostate cancer cell line models and propagate patient derived samples to allow drug testing and next generation sequencing as part of a precision medicine approach to early recurrent prostate cancer. METHODS: Patient derived metastatic tissue samples were collected as part of a larger clinical trial. These were digested in Type II Collagenase (Gibco) for 2 hours and seeded directly onto Collagen Type I coated plates in novel media. Samples were cultured in vitro for a minimum of 2 weeks prior to validation. PSA ELISA (GenWay Biotech) of conditioned media along with RT-qPCR comparison of various gene products of interest between cultured patient samples and established prostate cancer cell lines was performed. In vitro samples were subsequently utilised for therapeutic screening. RESULTS: A total of 5 patient samples were available for culture with histologically proven metastatic prostate cancer. Tissue from a 67 year old male with biochemical recurrence of prostate cancer following retro-pubic radical prostatectomy was obtained fresh at time of salvage lymph node dissection (PSA was 1.5 ng/ml). Tissue was successfully cultured for a minimum of 4 weeks prior to validation. PSA ELISA of conditioned media was positive. RT-qPCR confirmed expression of Prostate specific genes PSA, AR, FKBP5 and TMPRSS. Drug screen revealed a marked response to Docetaxel, Cabazitaxel and Enzalutamide and minimal effect to Bicalutamide. CONCLUSIONS: We have successfully cultured patient derived samples for precision medicine. Further therapeutic screening and next generation sequencing of derived cultures is ongoing in order to potentially inform therapeutic strategies. Organoid in vitro culture technology could provide a vital stepping stone towards precision medicine in the future, involving the rapid generation of patient specific in vitro models for therapeutic screening to guide individualized treatment.

Liposaccharides: Utilisation for peptide delivery and for enhancing synthetic peptide immunogenicity.

A user friendly, reliable delivery system is essential for the success of peptide-based drugs. Currently, there are many peptides and proteins that have the potential to be developed as new medicines. However, a lack of oral absorption and poor in vivo stability are major hurdles that must first be overcome, before any of these peptides or proteins will reach the clinic.