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Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

ABSTRACT: PURPOSE:Prostate circulating tumor cells escape into peripheral blood and enter bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease and existing detection methods rely on epithelial markers with low specificity and sensitivity. We used multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy. MATERIALS AND METHODS:Bone marrow was harvested from 208 clinically localized cases, 16 controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic cases. Samples were evaluated at 4 centers with 4 distinct platforms using antibody enrichment with the AdnaTest (Qiagen®) or VERSA (versatile exclusion based rare sample analysis), or whole sample interrogation with the RareCyte platform (Seattle, Washington) or HD-SCA (high definition single cell assay) using traditional epithelial markers and prostate specific markers. We investigated the sensitivity and specificity of these markers by evaluating expression levels in control and metastatic cases. RESULTS:EpCAM, NKX3.1 and AR were nonspecifically expressed in controls and in most samples using AdnaTest with no relation to perioperative variables. Only 1 patient with localized disease showed positive results for the prostate specific marker PSA. With the VERSA platform no localized case demonstrated disseminated tumor cells. With the RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor cell. CONCLUSIONS:Evaluation across multiple platforms revealed that epithelial markers are nonspecific in bone marrow and, thus, not suitable for disseminated tumor cell detection. Using prostate specific markers disseminated tumor cells were typically not detected in patients with localized prostate cancer.

SUBMITTER: Chalfin HJ

PROVIDER: S-EPMC5964005 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

Chalfin Heather J HJ Glavaris Stephanie A SA Malihi Paymaneh D PD Sperger Jamie M JM Gorin Michael A MA Lu Changxue C Goodwin C Rory CR Chen Yan Y Caruso Emily A EA Dumpit Ruth R Kuhn Peter P Lang Joshua M JM Nelson Peter S PS Luo Jun J Pienta Kenneth J KJ

The Journal of urology 20180112 6

<h4>Purpose</h4>Prostate circulating tumor cells escape into peripheral blood and enter bone marrow as disseminated tumor cells, representing an early step before conventionally detectable metastasis. It is unclear how frequently this occurs in localized disease and existing detection methods rely on epithelial markers with low specificity and sensitivity. We used multiple methodologies of disseminated tumor cell detection in bone marrow harvested at radical prostatectomy.<h4>Materials and metho ...[more]

PMID: 29339080

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Project description:BackgroundThe effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.MethodsFrom November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.ResultsDuring the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.ConclusionsAmong men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Project description:BackgroundSeveral studies have investigated the relationship between experience measured by caseload and oncological outcomes, economics, and access to care for prostate cancer care. Oncological outcomes have been limited to biochemical failure after radical prostatectomy. Questions remain regarding the more definitive measures of outcomes and their relationship with caseload.MethodsThe National Cancer Database was used to investigate the outcomes of radical prostatectomy in the United States. With overall survival (OS) as the primary outcome, the relationship between the facility annual caseload (FAC) for all prostate cancer encounters and the facility annual surgical caseload (FASC) for those requiring radical prostatectomy was examined with a Cox proportional hazards model. Four volume groups were defined by caseload: <50th percentile (volume group 1 [VG1]), 50th to 74th percentiles (volume group 2 [VG2]), 75th to 89th percentiles (volume group 3 [VG3]), and ≥90th percentile (volume group 4 [VG4]). By FAC/FASC, 11%/8%, 17%/18%, 25%/26%, and 47%/49% of patients were treated in VG1 through VG4, respectively.ResultsBetween 2004 and 2014, 488,389 patients underwent radical prostatectomy. At a median follow-up of 60.75 months, the median OS was not reached. There was a significant OS benefit as the caseload increased. For FAC, the adjusted OS difference between VG1 and VG4 at 90th percentile survivorship reached 13.2 months (hazard ratio [HR], 1.30; 95% CI, 1.23-1.36; P < .0001). For FASC, this was 11.3 months (HR, 1.25; 95% CI, 1.192-1.321; P < .0001).ConclusionsThere is a statistically significant OS advantage from performing radical prostatectomy at a facility with a high annual caseload. Caseload measured by all prostate cancer encounters is a better predictor of favorable outcomes than the number of surgeries performed at a facility.Lay summaryAn in-depth analysis of 488,389 cases of radical prostatectomy performed in more than 1000 facilities over a 10-year period showed better survival when surgery was performed in facilities with more experience and greater caseload. A survival difference of up to 13 months was observed when comparing patients treated at less experienced versus more experienced centers. Experience across all stages of prostate cancer was a stronger predictor of survival outcome than just the number of surgeries performed.

Project description:Accurate estimation of recurrence risk is needed for optimal treatment of clinically localized prostate cancer (PCa) patients. We combined classical clinicopathological predictors of biochemical recurrence (BCR) and molecular markers into a new risk score for predicting BCR after radical prostatectomy (RP). A retrospective study which included 122 PCa patients who attended our department between 2000 and 2007 was conducted. Total RNA was isolated from formalin-fixed paraffin embedded PCa tissue. Gene expression patterns were analyzed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in an independent retrospective series of 101 patients with ≥ 10 years follow-up who underwent RP for clinically localized PCa. Univariate and multivariate logistic regression analysis were used to identify individual predictors of BCR. A risk score (RS) for predicting BCR including clinicopathological and gene expression data was developed and Kaplan-Meier curves were generated. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. In a median follow-up of 120 months (range 3-190), 37 patients developed BCR (36.6%). Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A set of 41 genes were validated by quantitative PCR. Regression analysis showed that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion and positive margins were independent prognostic factors of BCR. A RS generated using these gene expression and clinicopathological variables was able to discriminate between two groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, p<0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the two genes of the model were not found. In conclusion, identification of new gene expression patterns associated with a high probability of BCR in clinically localized PCa patients treated with RP, and their combination with clinicopathological variables in a robust, easy-to-use and reliable classifier may contribute to improve PCa risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.

Project description:BackgroundThe minimum volume standard is 100 robot-assisted radical prostatectomy (RARP) procedures per hospital in the Netherlands, so patients have to be referred to high-volume surgical centers for RARP. During preoperative work-up, prostate biopsies taken elsewhere are reassessed, with upgrading or downgrading of the initial Gleason grade group a possible consequence.ObjectiveTo determine if prostate biopsy reassessment leads to adjustment of the surgical plan regarding a nerve-sparing approach and extended pelvic lymph node dissection (ePLND) during RARP.Design setting and participantsFor 125 men who were referred to the Prosper prostate center at Canisius Wilhelmina Hospital (CWH) in the Netherlands between 2013 and 2016, results for the initial assessment of prostate biopsy by a local uropathologist were compared to results for biopsy reassessment by dedicated uropathologists at CWH.Results and limitationsThe pathologists reached agreement in 80% of the cases. In cases for which there was disagreement (n = 25), biopsy revision involved upgrading of the initial grade group in 68% and downgrading in 32%. Biopsy reassessment led to a change in surgical plan in ten cases (8%). As a result of upgrading, ePLND was performed in three patients (2%). ePLND was omitted in one patient (1%) because of downgrading. For three patients (2%) a non-nerve-sparing procedure was planned after upgrading of the initial grade group. For four patients (3%), a unilateral nerve-sparing procedure was performed after downgrading.ConclusionsThis study shows that there is large interobserver agreement between uropathologists in the assessment of Gleason grade group in prostate biopsy specimens. Reassessment rarely leads to a change in surgical plan regarding the indication for a nerve-sparing approach and ePLND. Therefore, reassessment of prostate biopsy before radical prostatectomy can be omitted when the initial pathological assessment was performed by a dedicated uropathologist.Patient summaryReassessment of the initial prostate biopsy specimen for patients referred to a specialist center for robot-assisted removal of the prostate rarely influences surgical planning and can be omitted.

Project description:Background and objectiveProstate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP).MethodsTaking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications.ResultsPercentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05).ConclusionGNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker.

Project description:ImportanceThe cost-effectiveness of different surgical techniques for radical prostatectomy remains a subject of debate. Emergence of recent critical clinical data and changes in surgical equipment costs due to their shared use by different clinical specialties necessitate an updated cost-effectiveness analysis in a centralized, largely government-funded health care system such as the UK National Health Service (NHS).ObjectiveTo compare robotic-assisted radical prostatectomy (RARP) with open radical prostatectomy (ORP) and laparoscopic-assisted radical prostatectomy (LRP) using contemporary data on clinical outcomes, costs, and surgical volumes in the UK.Design, setting, and participantsThis economic analysis used a Markov model developed to compare the cost-effectiveness of RARP, LRP, and ORP to treat localized prostate cancer. The model was constructed from the perspective of the UK NHS. The model simulated 65-year-old men who underwent radical prostatectomy for localized prostate cancer and were followed up for a 10-year period. Data were analyzed from May 1, 2020, to July 31, 2021.ExposuresRobotic-assisted radical prostatectomy, LRP, and ORP.Main outcomes and measuresQuality-adjusted life-years (QALYs), costs (direct medical costs and costs outside the NHS), and incremental cost-effectiveness ratios (ICERs).ResultsCompared with LRP, RARP cost £1785 (US $2350) less and had 0.24 more QALYs gained; thus, RARP was a dominant option compared with LRP. Compared with ORP, RARP had 0.12 more QALYs gained but cost £526 (US $693) more during the 10-year time frame, resulting in an ICER of £4293 (US $5653)/QALY. Because the ICER was below the £30 000 (US $39 503) willingness-to-pay threshold, RARP was more cost-effective than ORP in the UK. The most sensitive variable influencing the cost-effectiveness of RARP was the lower risk of biochemical recurrence (BCR). Scenario analysis indicated RARP would remain more cost-effective than ORP as long as the BCR hazard ratios comparing RARP vs ORP were less than 0.99.Conclusions and relevanceThese findings suggest that in the UK, RARP has an ICER lower than the willingness-to-pay threshold and thus is likely a cost-effective surgical treatment option for patients with localized prostate cancer compared with ORP and LRP. The results were mainly driven by the lower risk of BCR for RARP. These findings may differ in other health care settings where different thresholds and costs may apply.

Dataset Information

Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

Publications

Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow of Patients with Localized Disease Undergoing Radical Prostatectomy across Multiple Rare Cell Detection Platforms.

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