RESUMO
OBJECTIVES: Cryoablation for prostate cancer is typically performed under general anaesthesia. We explore the safety, feasibility and costs of in-office MRI-targeted prostate partial gland cryoablation (PGC) under local anaesthesia. We hypothesise that an office-based procedure under local anaesthesia may yield greater patient convenience and lower health costs with similar outcomes to a general anaesthesia approach. DESIGN/PARTICIPANTS/SETTING/INTERVENTIONS: Retrospective study of men diagnosed with clinically significant prostate cancer (grade group (GG) ≥2) who elected to undergo in-office PGC under local anaesthesia. MAIN OUTCOME MEASURES: A total of 55 men with GG ≥2 prostate cancer underwent PGC under local anaesthesia, and 35 of 43 men (81.4%) who attained ≥6 months of follow-up post-treatment underwent MRI-targeted surveillance biopsy. We used MRI findings and targeted biopsy to characterise post-PGC oncological outcomes. Complications were categorised using Common Terminology Criteria for Adverse Events (CTCAE). Expanded Prostate Cancer Index-Clinical Practice was used to characterise urinary and sexual function scores at baseline, 4 and 9 months post-PGC. Time-driven activity-based costing was used to determine healthcare costs of in-office PGC. RESULTS: Five (9.1%) men experienced CTCAE score 3 adverse events. Urinary and sexual function did not change significantly from baseline to 4 months (p=0.20 and p=0.08, respectively) and 9 months (p=0.23 and p=0.67, respectively). Twenty-two men (62.9%) had no cancer or GG1 and 13 (37.1%) men had GG≥2 on post-PGC biopsy. Moreover, the median cost of in-office PGC was US$4,463.05 (range US$4,087.19-US7,238.16) with disposables comprising 69% of the cost. CONCLUSIONS: In-office PGC is feasible under local anaesthesia with favourable functional outcome preservation and adverse events profile at significantly lower costs compared with a general anaesthesia approach.
RESUMO
PURPOSE: For men with an elevated prostate-specific antigen (PSA), there is a strong evidence for prostate MRI to assess the risk of clinically significant prostate cancer (CSPC) and guide targeted-biopsy interventions. Prostate MRI is assessed using the Prostate Imaging-Reporting and Data System (PI-RADS), which is scored from 1 to 5. Equivocal or suspicious findings (PI-RADS 3-5) are recommended for subsequent targeted biopsy, for which the risk of infection and sepsis is increasing. However, PI-RADS was developed primarily in men of European descent. We sought to elucidate PI-RADS and MRI-targeted biopsy outcomes in Asian men, a rapidly growing population in the USA, Europe, Australia and internationally. MATERIALS AND METHODS: A prospective cohort of 544 men with elevated PSA without a diagnosis of prostate cancer who underwent MRI-targeted biopsy at our institution from January 2012 to December 2018 was analyzed. We categorized the cohort by self-designated race then used a validated algorithm which uses surname lists to identify a total of 78 (14%) Asian-Americans. The primary outcome was the likelihood of diagnosing CSPC (Gleason grade group >1) in Asian-Americans versus non-Asian-Americans. Multivariable logistic regression was used to determine the association of demographic and other characteristics with CSPC. RESULTS: Overall, MRI-targeted biopsy identified CSPC in 17% of Asian-American men versus 39% of non-Asian-American men (p<0.001). Notably for PI-RADS 3, only 6% of Asian-Americans versus 15% of others were diagnosed with CSPC. In adjusted analyses, Asian-American men were less likely to be diagnosed on MRI-targeted biopsy with CSPC (OR 0.30, 95% CI 0.14 to 0.65, p=0.002) and indolent prostate cancer (OR 0.37, 95% CI 0.15 to 0.91, p=0.030) than other races. Regardless of race those who were biopsy naïve were more likely (OR 2.25, 95% CI 1.45 to 3.49, p<0.001) to be diagnosed with CSPC. CONCLUSION: We found that PI-RADS underperforms in Asian-American men. For instance, only 2 of 35 (6%) Asian-American men with PI-RADS 3 were diagnosed with CSPC on MRI targeted biopsy. This has significant implications for overuse of diagnostic and image-guided interventional approaches in Asian-Americans, given the increasing risk of infectious complications from biopsy. Additional validation studies are needed to confirm our findings.
RESUMO
PURPOSE: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. PATIENTS AND METHODS: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic prostate cancer and at least one: small-cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; or elevated serum neuroendocrine markers. The primary endpoint was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed. RESULTS: Median PSA was 1.13 ng/mL (0.01-514.2), number of prior therapies was 3, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3-13). Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption. CONCLUSIONS: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib.