Wong, William W

AbstractPurpose/ObjectivesHolmium laser enucleation of the prostate (HoLEP) is commonly performed in patients with significant bladder outlet obstruction. However, there are few reports on the toxicity of external beam irradiation (RT) for prostate cancer in patients after prior HoLEP. In this study, we evaluate the side effects and treatment outcomes of RT after HoLEP.Materials/MethodsEighteen patients who had HoLEP and subsequently received RT for prostate cancer were included. Data collected included patient and disease characteristics, urinary function, and radiation dose. Acute and late urinary (GU) and gastrointestinal (GI) side effects were evaluated. Disease control and survival rates were calculated using Kaplan–Meier method.ResultsMedian follow‐up was 18 months (range: 4–46 months). Median prostate volume was 107 ml before HoLEP and 24 ml after HoLEP. Median International Prostate Symptom Score (IPSS) was 17 (range: 5–32) before HoLEP. Median decline in IPSS score after HoLEP was 7 (range: −2–21). On uroflow study, peak flow rate, and post‐void residual were significantly improved after HoLEP. After radiation, peak flow rate and average flow rate showed a decline but remained significantly improved compared to pre‐HoLEP measurements. Maximum acute Common Terminology Criteria for Adverse Events (CTCAE) adverse events were 12 grade 1 and 3 grade 2 for GU, and 3 grade 1 for GI, respectively. Maximum late adverse events were 13 grade 1 and 2 grade 2 for GU, and all grade 0 for GI, respectively. At last follow‐up, there were 8 grade 1 and 1 grade 2 late GU, and 3 grade 1 late GI adverse events, respectively. There was no significant increase in urinary incontinence after RT compared to before RT. The 18‐month biochemical control, local control, distant control rates were 78%, 94%, and 80%, respectively.ConclusionsPatients who received RT as definitive treatment for prostate cancer after prior HoLEP had low risk of serious acute and late side effects. HoLEP can be safely performed and should be considered in patients with significant bladder outlet obstruction and large prostate volume before RT.

Abstract Background Radium (Ra)‐223 is an established treatment option for patients with metastatic castrate‐resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP‐ribose polymerase inhibitors and platinum‐based therapies. This study aims to evaluate mCRPC response to Ra‐223 stratified by tumor genomics. Methods This is a retrospective study of mCRPC patients who received Ra‐223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate‐specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression‐free survival (PFS) and overall survival (OS) from time of first radium treatment. Results One hundred and twenty‐seven mCRPC patients treated with Ra‐223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra‐223 treatment was 61.0 and 68.6 years, respectively. Seventy‐nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2‐ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2‐ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0−NR) versus 26.8 months (95% CI 20.9−35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28−NR) versus 9.0 months (95% CI 7.3−11.1) and a lower OS 13.9 months (95% CI 5.2−NR) versus 26.5 months (95% CI 19.8−33.8). Conclusions Among mCRPC patients treated with Ra‐223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2‐ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra‐223.