Outcome Of Prostate Cancer Patients Research Articles

Outcomes Following Proton Therapy for the Treatment of Prostate Cancer: Efficacy and Toxicity Results from 2 Prospective Single Institution Cohorts

To report the outcomes of prostate cancer patients treated with definitive proton therapy at a single institution. The study population is the combination of two prospective single institution cohorts aimed at evaluating the efficacy and toxicity outcomes of prostate cancer patients treated with proton therapy. For this analysis, outcomes are presented according to NCCN risk group. Eligible patients had a non-pretreated prostate cancer with at least one year of follow-up following treatment. Results are presented as numbers and percentages and survival rates are computed using Kaplan Meier methods, using the end of radiotherapy as start date. Events for biochemical progression free survival (bPFS) are death, clinical or biochemical progression or salvage treatment. Events for clinical PFS (cPFS) are death, clinical progression or salvage treatment. From 2006 to 2015, 1869 prostate cancer patients were treated using proton therapy in these two cohorts, out of which 1628 (87%) had sufficient follow-up for inclusion in the present analysis (low-risk [LR]: n=516, 31.7%, intermediate risk [IR]: n=978, 60%, high-risk [HR]: n=134, 8.2%). Proton therapy delivered a median dose of 76 (range 75.6-78) cobalt gray equivalent (CGE) in 2 CGE fractions according to risk group. Pelvic lymph nodes were not treated. Hormonal therapy was mostly used for IR (56.7%) and HR (96.3%) patients. The median follow-up was 4.1 years for the entire cohort and 4.4, 4.1 and 3.1 years for LR, IR, and HR patients, respectively. Two/five-year overall survival rates were 100%/98.0%, 99.2%/95.9% and 99.2%/87.0% for LR, IR, and HR, respectively (p=0.004 for the differences between groups). Forty-four patients had died, of which 20 (45%) had died due to prostate cancer (5-years prostate cancer specific survival of 98% with no difference between groups, p=0.1). Two/five-year bPFS rates were 99.6%/95.7%, 97.9%/92.3% and 98.4%/80.7% for LR, IR, and HR, respectively (p=0.0001 for the differences between groups). Two/five-year cPFS rates were 99.8%/95.9%, 98.6%/92.7% and 98.0%/78.0% for LR, IR, and HR, respectively (p=0.0001 for the differences between groups). Acute grade 2+ genitourinary and gastrointestinal toxicity occurred in 39.4% (n=641) and 5.2% (n=85) of the entire cohort, with only 2 grade 3 GU and no grade 3 GI toxicity. Two/five-year cumulative incidence of late grade 2+ GU and GI toxicity, defined as occurring 90 days or more after treatment, was 10.4%/15.9% and 8.3%/10.6%, respectively. Late grade 3 and 4 GU toxicity occurred in 0.6% (n=9) and 0.1% (n=1) of patients, respectively. Late grade 3 and 4 GI toxicity occured in 0.6% (n=10) and 0.1% (n=1) of patients, respectively. This prospective single institution cohort of prostate cancer patients treated with proton therapy combined demonstrates the efficacy and safety of this treatment approach. These results need to be confirmed with a longer follow-up and compared with competing treatment options.

Weekly Integral Dose and Use of Lipid Lowering Drugs Are Associated With Worsening of Functional Outcomes in Prostate Cancer Patients Treated With IMRT

IMRT allows the delivery of highly conformal doses to target, but increases body integral dose due to irradiation of a larger volume of tissue at lower doses. We previously showed that higher weekly integral pelvic dose (weekID) was associated with adverse functional outcomes at RT end in patients (pts) with localized prostate cancer treated with IMRT (RO 2016). This analysis aimed to model worsening of functional and nonfunctional items from EORTC QLQ-C30, all plausibly related to fatigue. Patients from two prospective multicentric trials were evaluated, involving either conventional (78 Gy, 2 Gy/Fr) or hypo-fractionated (HF) (60-75.2 Gy, 2.35-3 Gy/Fr) RT alone, without lymph node irradiation. Collected clinical factors were: comorbidities, drugs, hormone therapies, previous surgeries, smoking, age, BMI. Integral dose was calculated as the product of mean body dose and body volume. WeekID was used to properly consider different fractionations. Worsening (RT end vs baseline) of EORTC QLQ-C30 scores in Physical/Role/Social Functioning scales and Fatigue was evaluated: 2 point worsening was considered for subscales including >2 items, 1 point worsening for 2 items subscales. Outcome measures for the analysis were defined as worsening in at least 2 (Wrs2) or 3 (Wrs3) subscales. Models incorporating weekID and clinical factors were developed using multivariable logistic regression (MVL). Complete data for 254 pts were available. The table summarizes the cohorts. The MVL for Wrs2 included weekID (OR = 1.05, continuous variable) and use of lipid lowering drugs (LLD, OR = 1.5). Calibration was good: slope = 1.01 (Rˆ2 = 0.80) in the development cohort and 1.05 (Rˆ2 = 0.90) in the validation dataset. The model for Wrs3 included the same factors (weekID OR = 1.06 and LLD OR = 2.3) with calibration slopes of 1.05 (Rˆ2 = 0.96) and 0.72 (Rˆ2 = 0.70), in the development and validation cohorts, respectively. Worsening of functional and non-functional quality of life symptoms was significantly associated with use of lipid lowering drugs and weekID, suggesting a higher impairment effect of hypofractionation in the acute phase (possible fraction size related inflammatory response or effect on blood cell counts). The effect of lipid lowering drugs is interesting, as they were found to be a risk factor for urinary toxicity in a large population (Palorini R&O 2016). These drugs are usually prescribed for vasculopathies: the present result thus bolsters the clue that pts with potential microangiopathic disease exhibit a possible enhanced sensitivity to RT-induced damage.

The outcome of prostate cancer patients treated with curative intent strongly depends on survival after metastatic progression

BackgroundFive-year survival in patients with localized prostate cancer (PCa) is nearly 100%, but metastatic disease still remains incurable. Clinical management of metastatic patients has become increasingly complex as novel therapeutic strategies have emerged. This study aims at evaluating the impact of the first metastatic progression on the outcome of PCa patients treated with curative intent.MethodsThe analysis was conducted using data of 913 cases of localized PCa diagnosed between 2000 and 2014. All patients were treated with curative surgery (N = 382) or radiotherapy (N = 531) with or without adjuvant therapy. All metastases were radiologically documented. The prognostic impact of the first site of metastasis on metastasis-free survival (MFS) and PCa-specific survival (PCaSS) was investigated by univariate and multivariate analyses.ResultsOne hundred and thirty-six (14.9%) patients developed a metastatic hormone-sensitive PCa and had a median PCaSS of 50.4 months after first metastatic progression. Bone (N = 50, 36.8%) and LN or locoregional (N = 52, 38.2%) metastases occurred more frequently with a median PCaSS of 39.7 and 137 months respectively (p < 0.0001). Seven patients developed visceral metastasis only (5.1%; liver, lung, brain) and 27 (19.9%) concurrent metastases; this last group was associated with the worst survival with a median value of only 17 months. Thus, each subgroup exhibited a survival after metastasis significantly different from each other. In multivariate analysis the site of the first metastasis was an independent prognostic factor for PCaSS along with Gleason score at diagnosis. The correlation between survival and first site of metastasis was confirmed separately for each therapy subgroup. Median metastasis-free survival from primary diagnosis to first metastasis was not correlated with the first site of metastasis.ConclusionsIn non-metastatic PCa patients treated with curative intent, the PCa-specific survival time depends on the time after metastatic progression rather than the time from diagnosis to metastasis. Moreover, the site of first metastasis is an independent prognostic factor for PCaSS. Our data confirm that the first metastatic event may confer a differential prognostic impact and may help in identifying patient at high risk of death supporting the treatment-decision making process following metastatic progression.

Reduced number of CD169+ macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients.

BackgroundTumor‐derived antigens are captured by CD169+ (SIGLEC1+) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti‐tumor immune response. Reduced CD169 expression in pre‐metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.MethodsCD169 expression was measured with immunohistochemistry in metastasis‐free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA‐relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan‐Meier survival‐ and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre‐metastatic LNs draining either highly metastatic MatLyLu‐ or poorly metastatic AT1‐tumors.ResultsIn patients with low CD169 immunostaining in metastasis‐free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining (P < 0.001). CD169 expression in regional LNs was not associated with PSA‐relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre‐metastatic regional LNs compared with rats with poorly metastatic tumors.ConclusionLow expression of CD169 in metastasis‐free regional LNs indicates a reduced anti‐tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.

801P - Effect of sequence on outcome of prostate cancer patients: retrospective study of a French cohort

801P - Effect of sequence on outcome of prostate cancer patients: retrospective study of a French cohort

Long-term oncological outcomes in patients with limited nodal disease undergoing radical prostatectomy and pelvic lymph node dissection without adjuvant treatment.

This study aimed at analysing long-term oncologic outcomes in prostate cancer patients with limited nodal disease (1-2 positive lymph nodes) without adjuvant therapy after radical prostatectomy (RP). We retrospectively analysed data of 209 pN1 patients who underwent RP between January 1998 and 2010 with one (160) or two (49) histologically proven positive lymph nodes (LNs) without adjuvant treatment. Biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival (CSS) were reported. In multivariable regression analyses further prognosticators of oncologic outcome in these patients were analysed. Median follow-up was 60.2months. There was no significant difference in oncologic outcome between patients with one and two positive LNs. 73.1% (76.7%) of patients with one (two) positive LNs had biochemical recurrence during the follow-up period, 20.0% (25.6%) developed metastasis and 8.1% (6.1%) died of their disease. The only factors significantly associated with oncologic outcome in multivariable analysis were Gleason score and pT-stage. Patients with limited nodal disease (1-2 positive LNs) without adjuvant therapy showed favourable CSS-rates above 94% after 5years. A subgroup of these patients (37%) remained metastasis-free without need of salvage treatment.

Heterogeneity of Outcomes in D'Amico Intermediate-Risk Prostate Cancer Patients after Radical Prostatectomy: Influence of Primary and Secondary Gleason Score

Aim: The aim of this study was to clarify and examine the outcomes of prostate cancer patients classified as intermediate risk (IR) using the D'Amico risk classification system, specifically focusing on the influence of primary and secondary biopsy Gleason score (BGS). Patients and Methods: An institutional review board-approved database of robotic-assisted radical prostatectomies performed after 2006 was stratified by standard D'Amico criteria. IR patients were then sub-stratified by BGS. Pathologic and intermediate-term biochemical disease-free survival (BDFS) outcomes were analyzed. Results: Overall, 1,090 patients were classified as D'Amico low-risk, 896 as IR, and 240 as high-risk. Of the 896 IR patients, 63 had BGS 6, 630 were 3 + 4 = 7, and 203 4 + 3 = 7. Among IR patients, as the BGS increased, there was an increasing likelihood of extracapsular extension (21, 28, and 38%, respectively; p = 0.005), positive surgical margins (14, 26, 31%; p = 0.048), and worse 3-year BDFS (96, 94, 88%; p = 0.01). Multivariable logistic regression and Cox regression analyses confirmed differences among IR groups. Conclusion: D'Amico IR patients demonstrate significant heterogeneity in both pathologic outcomes and BDFS. IR patients with a BGS of 6 appear to have similar intermediate-term BDFS as low-risk patients. An increasing BGS from 3 + 3 to 3 + 4 to 4 + 3 results in a higher likelihood of locally-advanced disease and intermediate-term biochemical failure.

Long-term Oncologic Outcomes of Robotic-assisted Radical Prostatectomy by a Single Surgeon

The aim of the study was to evaluate the long-term oncology outcomes of prostate cancer patients receiving robotic-assisted radical prostatectomy (RARP). We retrospectively evaluated 111 patients with clinically-localized prostate cancer receiving RARP with a mean follow-up of 103.43 months. The 5-year BCRFS and 8-year BCRFS among low-, intermediate-, and high-risk patients were 95.5% vs. 77.1% vs. 53.7% and 95.5% vs. 61.2% vs. 48.1% (p=0.000). The median time to BCR in these three groups was 122.5, 98.0, and 79.2 months. Regarding postoperative factors, positive lymph node (HR=3.748, 95% CI=1.407-9.984), pathology Gleason score (HR=1.507, 95%CI=1.010-2.248), and postoperative nadir PSA <0.003 ng/ml (HR=0.058, 95%CI=0.020-0.166) were independent risk factors for BCR. D'Amico risk classification was effective at predicting biochemical recurrence in patients receiving RARP. Furthermore, postoperative risk factors such as metastatic lymph node, pathology Gleason score, and nadir PSA <0.003 ng/ml were independent predictors of biochemical recurrence.

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

Background:Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers.Methods:Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy.Results:TOPK knockdown did not alter radiation response in normal tissues, but significantly enhanced radiosensitivity in cancer cells. This result was recapitulated in TOPK knockout cells and with the TOPK inhibitor, OTS964. TOPK depletion altered the G1/S transition and G2/M arrest in response to radiation. Furthermore, TOPK depletion increased chromosomal aberrations, multinucleation and apoptotic cell death after irradiation. These results suggest a possible role for TOPK in the radiation-induced DNA damage checkpoints. These findings have clinical relevance, as elevated TOPK protein expression was associated with poorer clinical outcomes in prostate cancer patients treated with radical radiotherapy.Conclusions:This study demonstrates that TOPK disruption may cause tumour-specific radiosensitisation in multiple different tumour types.

Abstract 557: SPOP mutant subclass prediction and its impact on prostate cancer prognosis

Abstract SPOP mutations define a distinct and key molecular class of prostate cancer, but there is no signature to identify SPOP mutant subclass based on transcriptional data, and its impact on prognosis and clinical outcomes of prostate cancer patients is unknown. We developed the SPOP mutant transcriptional signature with high sensitivity and specificity based on transcriptional data. After we predicted SPOP mutant subclass from a large cohort project with transcriptional signature, we studied its association with clinicopathologic variables and prognosis in prostate cancer patients. On univariate analysis, SPOP mutant subclass was associated with lower preoperative serum prostate-specific antigen, extraprostatic extension and older patients (p&amp;lt;0.05). On multivariate analysis, SPOP mutant subclass was associated with metastasis (p&amp;lt;0.05). Combined SPOP mutant status and CAPRA-S models have slightly better prediction for metastasis. On Kaplan-Meier analysis, we found the significant association of SPOP mutant subclass with better patient outcomes of metastasis, and patients without radiation therapy with even better metastatic outcomes. The SPOP mutant subclass could be predicted by using our SPOP mutant signature purely based on transcriptional data. Clinical and prognosis difference were found among SPOP mutant subclass. Citation Format: Deli Liu. SPOP mutant subclass prediction and its impact on prostate cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 557. doi:10.1158/1538-7445.AM2017-557

Optimum Tools for Predicting Clinical Outcomes in Prostate Cancer Patients Undergoing Radical Prostatectomy: A Systematic Review of Prognostic Accuracy and Validity.

Prostate cancer is a heterogeneous disease whose therapies frequently have adverse effects. Informed patient counseling regarding likely clinical outcomes is therefore important. In this systematic review we aimed to identify all external validations of tools that are used to predict clinical outcomes in patients undergoing radical prostatectomy and evaluate which are optimum for clinical implementation. PubMed and EMBASE were searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, radical prostatectomy, and prognosis. Titles and abstracts were screened and relevant studies were advanced to full-text review. Reference lists were reviewed for further studies. The Centre for Evidence Based Medicine prognostic tool was used for critical appraisal. Seventy-three studies externally validated 13 pre- and 41 postoperative tools for the prediction of biochemical recurrence (BCR), aggressive BCR, metastasis, and prostate cancer-specific mortality (PCSM). Recommendations for clinical implementation were made on the basis of accuracy, cohort sizes, and consistency. The accuracy of recommended tools ranged from 68% to 79% and 72% to 92% among the largest validation cohorts for pre- and postoperative tools. For preoperative prognosis we recommended the Cancer of the Prostate Risk Assessment (CAPRA) and Stephenson nomograms for BCR, the CAPRA nomogram for aggressive BCR as well as metastasis, and the D'Amico criteria for PCSM. For postoperative prognosis we recommended the CAPRA-Surgery (CAPRA-S), Stephenson, Kattan, Duke prostate cancer (DPC), and the Suardi nomograms for the prediction of BCR, the DPC nomogram for aggressive BCR, the CAPRA-S and Eggener nomograms for metastasis, and the Eggener nomogram for PCSM. Use of these tools should help clinicians deliver accurate, evidence-based counseling to patients undergoing prostatectomy.

Tools for predicting patient-reported outcomes in prostate cancer patients undergoing radical prostatectomy: a systematic review of prognostic accuracy and validity.

Radical prostatectomy is a common surgical procedure performed to treat prostate cancer. Patient-reported outcomes after surgery include urinary incontinence, erectile dysfunction, decreased quality of life and psychological effects. Predictive tools to assess the likelihood of an individual experiencing various patient-reported outcomes have been developed to aid decision-making when selecting treatment. A systematic review was undertaken to identify all papers describing tools for the prediction of patient-reported outcome measures in men with prostate cancer treated with radical prostatectomy. To be eligible for inclusion, papers had to provide a summary measure of accuracy. PubMed and EMBASE were searched from July 2007. Title/abstract screening, and full-text review were undertaken by two reviewers, while data extraction and critical appraisal was performed by a single reviewer. The search strategy identified 3217 potential studies, of which 191 progressed to full-text review and 14 were included. From these studies, 27 tools in total were identified, of which 18 predicted urinary symptoms, six predicted erectile function and one predicted freedom from a group of three outcomes ('trifecta') (biochemical recurrence, incontinence and erectile dysfunction). On the basis of tool accuracy (>70%) and external validation, two tools predicting incontinence and two tools predicting erectile dysfunction are ready for implementation. A small number of tools for the prediction of patient-reported outcomes following radical prostatectomy have been developed. Four tools were found to have adequate accuracy and validation and are ready for implementation for the prediction of urinary incontinence and erectile dysfunction.

Accounting for improved prostate cancer mortality outcomes in Haitian men: A histological analysis.

e16557 Background: In a previous wide-ranging study on the outcomes of prostate cancer patients at a safety-net hospital, we discovered significantly improved mortality outcomes for Haitian Creole prostate cancer patients compared to all other languages spoken, including black English speakers, with p = 0.017 [Rand, AE, et al., Clin Genitourin Cancer. (6):455-60 (2014)]. In order to assess any molecular indications that could be contributing to this finding, we performed a histological analysis of prostate cancer specimens, comparing black English-speaking patients to Haitian Creole patients. Methods: We sampled prostatectomies from 34 black English-speaking patients and 38 black Haitian Creole-speaking patients, taken between December 2011 and June 2015. In addition to primary and secondary Gleason scores, extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and perineural invasion (PNI), we observed any small amounts of grade 5 tissue present for the tertiary Gleason score. Finally, we analyzed the presence of acute and chronic inflammation and inflammatory severity. A chi square analysis was used to compare the categories between the Haitian and non-Haitian sets, with a probability less than 0.05 considered statistically significant. Results: While the null hypothesis was confirmed for primary, secondary, and total Gleason scores, 23.7% of the Haitian samples had a tertiary Gleason score of 5, compared to only 6.3% of non-Haitian samples (p = 0.046). The two populations exhibited similar rates of EPE (p = 0.719), SVI (p = 0.884), and PNI (p = 0.597), with no LVI apparent in any sample. No significant trends were noted in acute vs. chronic inflammation (p = 0.402) or severity of inflammation (p = 0.601). Conclusions: Samples taken from Haitian Creole-speaking patients had a significantly higher rate of grade 5 tertiary Gleason tissue than the non-Haitian patient samples. The presence of a tertiary Gleason score indicates a higher risk of metastasis, yet the Haitian samples do not reveal a greater rate of extraprostatic invasion. Further studies investigating underlying health factors among Haitian patients might be useful in accounting for improved patient outcomes.

(P033) Do Sociodemographic Factors and Comorbidities Significantly Influence Outcome in Prostate Cancer Patients Treated With External Beam Radiation Therapy?

(P033) Do Sociodemographic Factors and Comorbidities Significantly Influence Outcome in Prostate Cancer Patients Treated With External Beam Radiation Therapy?

The role of whole-lesion apparent diffusion coefficient analysis for predicting outcomes of prostate cancer patients on active surveillance.

To explore the role of whole-lesion apparent diffusion coefficient (ADC) analysis for predicting outcomes in prostate cancer patients on active surveillance. This study included 72 prostate cancer patients who underwent MRI-ultrasound fusion-targeted biopsy at the initiation of active surveillance, had a visible MRI lesion in the region of tumor on biopsy, and underwent 3T baseline and follow-up MRI examinations separated by at least one year. Thirty of the patients also underwent an additional MRI-ultrasound fusion-targeted biopsy after the follow-up MRI. Whole-lesion ADC metrics and lesion volumes were computed from 3D whole-lesion volumes-of-interest placed on lesions on the baseline and follow-up ADC maps. The percent change in lesion volume on the ADC map between the serial examinations was computed. Statistical analysis included unpaired t tests, ROC analysis, and Fisher's exact test. Baseline mean ADC, ADC0-10th-percentile, ADC10-25th-percentile, and ADC25-50th-percentile were all significantly lower in lesions exhibiting≥50% growth on the ADC map compared with remaining lesions (all P≤0.007), with strongest difference between lesions with and without≥50% growth observed for ADC0-10th-percentile (585±308 vs. 911±336; P=0.001). ADC0-10th-percentile achieved highest performance for predicting≥50% growth (AUC=0.754). Mean percent change in tumor volume on the ADC map was 62.3%±26.9% in patients with GS≥3+4 on follow-up biopsy compared with 3.6%±64.6% in remaining patients (P=0.050). Our preliminary results suggest a role for 3D whole-lesion ADC analysis in prostate cancer active surveillance.

Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients.

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34–19.80) and 12.83 (95% CI: 2.16–26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.

PD47-11 OPTIMUM TOOLS FOR PREDICTING CLINICAL OUTCOMES IN PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY: A SYSTEMATIC REVIEW OF PROGNOSTIC ACCURACY AND VALIDITY

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2017PD47-11 OPTIMUM TOOLS FOR PREDICTING CLINICAL OUTCOMES IN PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY: A SYSTEMATIC REVIEW OF PROGNOSTIC ACCURACY AND VALIDITY Jared Campbell, Elspeth Raymond, Michael O'Callaghan, Andrew Vincent, Kerri Beckmann, David Roder, Sue Evans, John McNeil, Jeremy Millar, John Zalcberg, Martin Borg, and Kim Moretti Jared CampbellJared Campbell More articles by this author , Elspeth RaymondElspeth Raymond More articles by this author , Michael O'CallaghanMichael O'Callaghan More articles by this author , Andrew VincentAndrew Vincent More articles by this author , Kerri BeckmannKerri Beckmann More articles by this author , David RoderDavid Roder More articles by this author , Sue EvansSue Evans More articles by this author , John McNeilJohn McNeil More articles by this author , Jeremy MillarJeremy Millar More articles by this author , John ZalcbergJohn Zalcberg More articles by this author , Martin BorgMartin Borg More articles by this author , and Kim MorettiKim Moretti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2371AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer progresses slowly, but its therapies often have adverse effects. Informed patient counselling regarding clinical outcomes is therefore important. The objective of this study was to identify all external validations of tools that predict clinical outcomes in prostate cancer patients undergoing radical prostatectomy, and evaluate which are optimum for clinical implementation. METHODS PubMed and Embase were systematically searched from 2007 to 2016. Search terms related to the inclusion criteria: prostate cancer, clinical outcomes, radical prostatectomy and prognosis. Titles/abstracts were screened and relevant studies were advanced to full-text review. The references of full-texts were reviewed for further studies. The Centre for Evidence-Based Medicine prognostic study tool was used for critical appraisal and the online tool Covidence was used for data extraction. RESULTS Seventy-three studies externally validated 41 post- and 13 pre-operative tools for the prediction of biochemical recurrence (BCR), aggressive BCR, metastasis, and prostate cancer specific mortality (PCSM). Recommendations for clinical implementation were made based on accuracy, cohort sizes, number of validations, and consistency. The accuracy of recommended tools ranged from 72-92% and 68-79% amongst the largest validation cohorts for post- and pre-operative tools, respectively. For post-operative prognosis we recommend the CAPRA-S, Stephenson, Kattan, DPC and the Suardi nomograms for the prediction of BCR, the DPC nomogram for aggressive BCR, the CAPRA-S and Eggener nomograms for metastasis, and the Eggener nomogram for PCSM. For pre-operative prognosis we recommend the CAPRA and Stephenson nomograms for BCR, the D′Amico criteria for aggressive BCR, the CAPRA nomogram for metastasis, and the D′Amico criteria for PCSM. CONCLUSIONS We identified all tools that can be used to predict clinical outcomes for prostate cancer patients undergoing radical prostatectomy. While many were inaccurate or not well validated, we recommend the best available tools to help clinicians give patients accurate predictions. Use of these tools should help clinicians deliver accurate, evidence based counselling to patients undergoing radical prostatectomy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e900 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jared Campbell More articles by this author Elspeth Raymond More articles by this author Michael O'Callaghan More articles by this author Andrew Vincent More articles by this author Kerri Beckmann More articles by this author David Roder More articles by this author Sue Evans More articles by this author John McNeil More articles by this author Jeremy Millar More articles by this author John Zalcberg More articles by this author Martin Borg More articles by this author Kim Moretti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP47-12 IMPACT OF PROXIMITY TO NCI- AND NCCN-DESIGNATED CANCER CENTERS ON OUTCOMES FOR PATIENTS WITH PROSTATE CANCER UNDERGOING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV1 Apr 2017MP47-12 IMPACT OF PROXIMITY TO NCI- AND NCCN-DESIGNATED CANCER CENTERS ON OUTCOMES FOR PATIENTS WITH PROSTATE CANCER UNDERGOING RADICAL PROSTATECTOMY Cameron Ghaffary, Zhigang Duan, Brian Chapin, Tamer Dafashy, Christopher Kosareck, Karim Chamie, Simon Kim, Thomas Ahlering, John Davis, Sharon Giordano, and Stephen Williams Cameron GhaffaryCameron Ghaffary More articles by this author , Zhigang DuanZhigang Duan More articles by this author , Brian ChapinBrian Chapin More articles by this author , Tamer DafashyTamer Dafashy More articles by this author , Christopher KosareckChristopher Kosareck More articles by this author , Karim ChamieKarim Chamie More articles by this author , Simon KimSimon Kim More articles by this author , Thomas AhleringThomas Ahlering More articles by this author , John DavisJohn Davis More articles by this author , Sharon GiordanoSharon Giordano More articles by this author , and Stephen WilliamsStephen Williams More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1472AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). METHODS A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs RESULTS Patients with proximity to =2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p<0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p=0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. CONCLUSIONS Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e632-e633 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Cameron Ghaffary More articles by this author Zhigang Duan More articles by this author Brian Chapin More articles by this author Tamer Dafashy More articles by this author Christopher Kosareck More articles by this author Karim Chamie More articles by this author Simon Kim More articles by this author Thomas Ahlering More articles by this author John Davis More articles by this author Sharon Giordano More articles by this author Stephen Williams More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Tools for Predicting Clinical and Patient-reported Outcomes in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Systematic Review of Prognostic Accuracy and Validity.

Androgen deprivation therapy (ADT) can result in a range of adverse symptoms that reduce patients' quality of life. Careful patient counseling on the likely clinical outcomes and adverse effects is therefore vital. The present systematic review was undertaken to identify and characterize all the tools used for the prediction of clinical and patient-reported outcome measures (PROMs) in patients with prostate cancer undergoing ADT. PubMed and EMBASE were systematically searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, PROMs, ADT, and prognosis. Titles and abstracts were reviewed to find relevant studies, which were advanced to full-text review. The reference lists were screened for additional studies. The Centre for Evidence Based Medicine critical appraisal of prognostic studies tool was applied. The search strategy identified 8755 studies. Of the 8755 studies, 22 on clinical outcomes were identified. However, no studies of PROMs were found. Nine tools could be used to predict clinical outcomes in treatment-naive patients and 10 in patients with recurrence. The Japan Cancer of the Prostate Risk Assessment (J-CAPRA) nomogram was the best performing and validated tool for the prediction of clinical outcomes in treatment-naive patients, and the Chi and Shamash prognostic indexes have been validated for use in patients with castration-resistant disease in different clinical contexts. Using the J-CAPRA nomogram should help clinicians deliver accurate, evidence-based counseling to patients undergoing primary ADT. A strong need exists for primary studies that derive and validate tools for the prediction of PROMs in patients undergoing ADT under any circumstance because these are currently absent from the literature.

Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms.

Background: Prostate cancer (PCa) is a critical health burden, impacting the morbidity and mortality of millions of men around the world. Most of the patients with PCa have their disease at first sensitive to androgen deprivation treatments, but later they develop resistance to therapy and eventually die of metastatic castration-resistant prostate cancer (CRPC). Although the newly developed anti-androgen therapies are effectively alleviating symptoms and prolonging lives of patients, there are still no curable treatments for CRPC. Recently, statistical studies have shown that the chronic use of aspirin might be significantly associated with better outcomes in PCa patients. Through this review, we aim to identify the different proposed molecular mechanisms relating aspirin to the pathobiology of PCa neoplasms, with a major focus on basic research done in this context.Methods: Articles were retrieved via online database searching of PubMed and MEDLINE between 1946 and September 2016. Keywords and combinations related to PCa and aspirin were used to perform the search. s of the articles were studied by two independent reviewers and then data extraction was performed on the relevant articles that met our review objectives.Results: Aspirin, a non-steroidal anti-inflammatory drug (NSAID), affects the proliferation, apoptosis, resistance and metastasis of PCa cell lines, through both COX-dependent and COX-independent mechanisms. It also lowers levels of the PCa diagnostic marker prostate specific antigen (PSA), suggesting that clinicians need to at least be aware if their patients are using Aspirin chronically.Conclusion: This review strongly warrants further consideration of the signaling cascades activated by aspirin, which may lead to new knowledge that might be applied to improve diagnosis, prognosis and treatment of PCa.