Does Valproic Acid Induce Neuroendocrine Differentiation in Prostate Cancer?

Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome with Nephron-sparing Surgery in a Patient with von Hippel-Lindau.

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC

MRI-guided focal laser ablation of prostate cancer: a prospective single-arm, single-center trial with 3 years of follow-up

PURPOSEWe aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance imaging (mpMRI).METHODSFLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months.RESULTSFifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy).CONCLUSIONAfter 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications

Molecular biomarkers in the context of focal therapy for prostate cancer: Recommendations of a delphi consensus from the focal therapy society

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject

Metastatic Directed Therapy in Oligometastatic Prostate Cancer

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Reliability of Systematic and Targeted Biopsies versus Prostatectomy

Systematic Biopsy (SBx) has been and continues to be the standard staple for detecting prostate cancer. The more expensive MRI guided biopsy (MRITBx) is a better way of detecting cancer. The prostatectomy can provide an accurate condition of the prostate. The goal is to assess how reliable SBx and MRITBx are vis à vis prostatectomy. Graded Gleason scores are used for comparison. Cohen’s Kappa index and logistic regression after binarization of the graded Gleason scores are some of the methods used to achieve our goals. Machine learning methods, such as classification trees, are employed to improve predictability clinically. The Cohen’s Kappa index is 0.31 for SBx versus prostatectomy, which means a fair agreement. The index is 0.34 for MRITBx versus prostatectomy, which again means a fair agreement. A direct comparison of SBx versus prostatectomy via binarized graded scores gives sensitivity 0.83 and specificity 0.50. On the other hand, a direct comparison of MRITBx versus prostatectomy gives sensitivity 0.78 and specificity 0.67, putting MRITBx on a higher level of accuracy. The SBx and MRITBx do not yet match the findings of prostatectomy completely, but they are useful. We have developed new biomarkers, considering other pieces of information from the patients, to improve the accuracy of SBx and MRITBx. From a clinical point of view, we provide a prediction model for prostatectomy Gleason grades using classification tree methodology

Traditional and novel imaging modalities for advanced prostate cancer: A critical review

Accurate detection of metastatic prostate cancer in the setting of preoperative staging as well as posttreatment recurrence is crucial to provide patients with appropriate and timely treatment of their disease. This has traditionally been accomplished with a combination of computed tomography, magnetic resonance imaging, and bone scan. Recently, more novel imaging techniques have been developed to help improve the detection of advanced and metastatic prostate cancer. This review discusses the efficacy of the traditional imaging modalities as well as the novel imaging techniques in detecting metastatic prostate cancer. Articles discussed were gathered through a formal PubMed search