Genetics of neuroendocrine prostate cancer: recent progress in genetic understanding is translating into therapeutic opportunities.

PURPOSE OF REVIEW: Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype of prostate cancer with extremely aggressive clinical behaviour and very limited data regarding treatment options. This review is intended to relay new research advances in the understanding of the genetic and epigenetic aberrations underlying NEPC development and to review new targeted therapeutic options developed based on NEPC genetics. RECENT FINDINGS: Multiple genomic alterations and epigenetic regulators have been identified in NEPC development. Among these are amplifications of oncogenic transcriptional factors, changes in expression of cell surface markers and epigenetic alterations. This in turn has facilitated a number of new targeted therapies for NEPC that act via different mechanisms including catalytic inhibitors, immune-modulators and epigenetic modifiers. These targeted therapies are now being studied in different phases of clinical trials with some preliminary results showing efficacy. SUMMARY: NEPC is a highly aggressive malignancy with currently lack of effective treatments. Considerable challenges still remains to improve clinical outcomes in NEPC; however, ongoing trials exploiting novel genetic and epigenetic alterations hold promise for patients suffering from this aggressive disease.

A comparison between 68Ga-labeled prostate-specific membrane antigen-PET/CT and multiparametric MRI for excluding regional metastases prior to radical prostatectomy.

OBJECTIVES: To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). MATERIALS AND METHODS: A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10 mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. RESULTS: Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively. CONCLUSIONS: PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

Comparison of Partial and Radical Laparascopic Nephrectomy: Perioperative and Oncologic Outcomes for Clinical T2 Renal Cell Carcinoma.

INTRODUCTION: Nephron-sparing surgery has emerged as the treatment of choice for small renal masses. However, its role in larger tumors remains controversial. In this study, we compare the outcomes of laparoscopic partial nephrectomy (LPN) vs those of laparoscopic radical nephrectomy (LRN) for T2 renal tumors. MATERIALS AND METHODS: Thirteen patients who had LPN and 16 patients who had LRN for T2 renal tumors were retrospectively analyzed for preoperative factors (age, gender, comorbidities, hemoglobin, and creatinine levels and estimated glomerular filtration rate [eGFR]), operative and perioperative characteristics (tumor characteristics, operative time [OT], warm ischemia time [WIT], estimated blood loss [EBL], length of stay [LOS], and postoperative complications), histopathologic results, and follow-up data (eGFR and recurrences). RESULTS: Tumor size was comparable between groups; however, tumors in the LRN group were more endophytic, central, and closer to the collecting system. There were no cases of positive surgical margins. Median OT was 160 minutes vs 230 minutes (p = 0.0029) and EBL was 25 mL vs 100 mL ([p = 0.0027], LRN vs LPN). Median WIT in the LPN group was 27 minutes, with three zero ischemias. Minor postoperative complications (≤Clavien-Dindo III) were noted in 6.25% and 23% (LRN vs LPN). Median LOS was 4.56 and 5.77 days (LRN vs LPN), respectively. Mean postsurgery eGFR was significantly lower for the LRN group (54.5 cc/[min ·1.73 m2] vs 76.3 cc/[min ·1.73 m2], p = 0.019). Within mean follow-up of 44.5 months, one tumor recurrence in the contra lateral kidney was observed in the LPN group and two cases of metastasis in the LRN group. CONCLUSIONS: We show that LPN is technically feasible for T2 tumors, with acceptable intra- and perioperative outcomes. Furthermore, our results show a significant advantage in preservation of renal function for LPN without compromising oncologic results. Taken together, we believe that LPN should be considered for larger tumors based on technical feasibility rather than only tumor size.