Objective To compare the long-term outcome of arti®cial urinary sphincter (AUS) implantation in patients after prostatectomy, with and with no history of previous irradiation. Patients and methods The study included 98 men (mean age 68 years) with urinary incontinence after prostatectomy for prostate cancer (85 radical, 13 transurethral resection) who had an AUS implanted. Twenty-two of the patients had received adjuvant external beam irradiation before AUS implantation. Over a mean (range) follow-up of 46 (5±118) months, the complication and surgical revision rates were recorded and compared between irradiated and unirradiated patients. The two groups were also compared for the resolution of incontinence and satisfaction, assessed using a questionnaire. Results Overall, surgical revision was equally common in irradiated (36%) and unirradiated (24%) patients.After activating the AUS, urethral atrophy, infection and erosion requiring surgical revision were more common in irradiated patients (41% vs 11%; P<0.05); 70% of patients reported a signi®cant improvement in continence, regardless of previous irradiation. Patient satisfaction remained high, with >80% of patients stating that they would undergo surgery again and/or recommend it to others, despite previous irradiation and/or the need for surgical revision. Conclusions Despite higher complication and surgical revision rates in patients who have an AUS implanted and have a history of previous irradiation, the longterm continence and patient satisfaction appear not to be adversely affected.
Background: Intermediate and high-risk prostate cancer patients are candidates for radiotherapy (RT). Evidence has shown that the presence of circulating tumor cells (CTCs) correlates with poor overall survival for patients with metastatic prostate cancer. CTCs have been reported as a better earlier predictor of treatment response than evaluation of prostate-specific antigen (PAS). The aim of our study was to identify and quantify circulating tumor cells from the peripheral blood of patients enrolled in two randomized Phase II radiotherapy clinical trials (BLaStM, NCT02307058 and CoMBINe, NCT02997709). Moreover, we investigated the genomic profiling of single CTCs using 10X Genomics to explore prognostic factors. Design/Methods: CTCs were successfully harvested and enumerated from more than 215 patients and 500 blood samples using a microfilter system, the Circulogix FaCTChecker, and the cells of interest enriched onto CyteCatch slides. Circulating tumor cells were visualized by staining, identified and quantified for epithelial and prostate specific markers. The number of single CTCs, CTC clusters and their sum were recorded. Unfixed CTCs were enriched from whole blood from 13 prostate cancer patients at high risk of metastasis (median age of 63.5 years and median CTC value of 12 (range 0-42)) using The Parsortix™ Cell Separation System (ANGLE Inc.), a microfluidic-based platform able to capture and harvest CTCs, and single-cell RNA sequencing was then performed with Chromium (10X Genomics) and Illumina NGS sequencing technologies. Initial bioinformatic and data analysis was performed by the Biostatistics and Bioinformatics Shared Resource (BBSR) at SCCC. Subsequent principal component analysis (PCA) and gene set enrichment analysis (GSEA) were performed. Meanwhile, patient demographic and disease characteristic variables (PSA, Gleason Score (GS), T stage, % tumor in biopsies, age, race/ethnicity) were also collected and compared. Results: Single CTCs or CTC clusters were evident in over 70% of patients analyzed using Immunofluorescence staining, with a median number of 30 (range 0-346). CTC transcriptomes at the single cell level was performed using the 10X platform, and principal component analysis discovered 16 distinct cell clusters of differential gene signatures within these cells in a t-SNE plot. Gene ontology analysis found some of these cell clusters contain differential expression pathways such as mTOR signaling (p=5.82E-05), EIF2 signaling (p=7.90E-05) and regulation of eIF4 and p70S6K signaling (p= 1.04E-04) which have been associated with prostate cancer. Gene Set Enrichment Analysis also identified distinct differential expression pathways in prostate CTCs comparing with non-CTCs. Conclusion: We have developed a novel pipeline to harvest CTCs and analyze transcriptomes at the single-cell level. Our results suggest that gene expression profiling of CTCs can be a promising way to explore prognostic markers for predicting radiation sensitivity and metastatic risk. Citation Format: Teresa Giret, Wensi Tao, Robert Suter, Saba Ansari, Sion Williams, Nagi Ayad, Radka Stoyanova, Brian Marples, Alan Pollack. Analysis of circulating tumor cells from prostate cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5362.
80 Background: To assess the prognostic value of percentage of positive biopsy cores (PPC) and perineural invasion (PNI) in predicting clinical outcome following radiotherapy (RT) for prostate cancer. Methods: One thousand and fifty-six patients with clinical stage T1-T3 N0 M0 prostate cancer, who had ≥ 4 biopsy cores sampled and complete biopsy core data available, were treated with either adaptive image-guided RT (median 75.6 Gy, n=387), low-dose EBRT (median 66.6 Gy, n=393), or EBRT and high-dose rate brachytherapy boost (n=276) at William Beaumont Hospital (1993-2004). Neoadjuvant and/or adjuvant androgen deprivation (AD) were given to 253 patients (24%). Multivariate cox regression analysis included PPC, gleason score, PSA, T stage, PNI, RT dose, androgen deprivation, and age. Biochemical failure (BF) was scored according to the Phoenix definition. Clinical failure (CF) was defined as any locoregional recurrence (LRR) or distant metastasis (DM). Median follow-up was 7.6 years. Results: Median cores sampled was 7, median PPC was 33%, and 18% had PNI. On univariate Cox regression, both PPC and PNI were predicators of biochemical failure and clinical failure (all P<0.05). On multivariate Cox regression, PPC, either as continuous or categorical variable, remained an independent predicator of BF, CF, DM, cause-specific survival, and overall survival (all P<0.05). PPC of >50% was associated with significantly higher DM (HR 4.01, 95% CI 1.86-8.61), and its independent predicative value remained significant whether AD was given or not (all P<0.05). Combining ≤50% vs ≥50% PPC with NCCN risk group stratification demonstrated added prognostic value of DM for intermediate-risk (HR 5.44, 95% CI 1.78-16.6) and high-risk groups (HR 4.39, 95% CI 1.70-2.84), with or without AD (all P<0.05). On multivariate Cox regression, PNI was an independent predicator of LRR only (HR 2.51, 95% CI 1.18-5.33). Conclusions: PPC is an independent and powerful predicator of DM for intermediate- and high-risk prostate cancer, regardless the use of AD. It should be considered for risk stratification and when designing for future trials testing adjuvant treatment after definitive RT for prostate cancer. No significant financial relationships to disclose.
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