Organ-confined Disease Research Articles

Cribriform morphology predicts upstaging after radical prostatectomy in patients with Gleason score 3 + 4 = 7 prostate cancer at transrectal ultrasound (TRUS)-guided needle biopsy.

Selected patients with transrectal ultrasound (TRUS)-guided biopsies containing Gleason score 3 + 4 = 7 prostate cancer (PCa) may be considered candidates for active surveillance (AS). The purpose of this study was to determine if there are features that predict PCa upstaging and/or upgrading after radical prostatectomy (RP) in patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsies. We searched our institution's database for patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy who underwent subsequent RP between January 2010 and January 2015. Two blinded genitourinary pathologists independently reviewed and assessed the following on biopsies: (a) nuclear size, nucleolar size and distribution of macronucleoli of PCa, which were subjectively graded using a semi-quantitative scale from 1 to 3, and (b) PCa with cribriform morphology and the size of cribriform disease. Patient age, serum prostate-specific antigen (PSA) and PSA density (PSAD) were also recorded. The Gleason score and stage (presence or absence of organ-confined disease (OCD)) were retrieved from RP reports. Comparisons were performed between groups using the chi-square test and Spearman correlation. One hundred and four patients were identified to have met inclusion criteria. The mean age was 63 (±6.1) years. Mean PSA and PSAD at diagnosis were 7.5 (±4.2) and 0.25 (±0.15) ng/mL, respectively. Gleason scores were upgraded to greater than 3 + 4 = 7 in 26.9 % (28/104) of patients, and 44.2 % (46/104) of patients had no OCD after RP. There was no correlation between age, PSA, PSAD or percent of biopsies with Gleason pattern 4 for either Gleason score upgrading or absence of OCD at the time of RP (p > 0.05). Thirty patients had cribriform morphology on TRUS-guided biopsy of which 60 % (18/30) had no OCD at RP (p = 0.04) while 36.7 % (11/30) were upgraded to Gleason score ≥3 + 4 = 7 after RP (p = 0.15). There was no association between nuclear size, nucleolar size and/or distribution of macronucleoli with upgrading and/or absence of OCD (p > 0.05). The size of cribriform pattern was not associated with the absence of OCD (p = 0.43) or Gleason score upgrade (p = 0.28). A proportion of patients with Gleason score 3 + 4 = 7 PCa at needle biopsy do not have OCD or are upgraded to higher Gleason scores after RP. In our study, patients with Gleason score 3 + 4 = 7 PCa with the presence of cribriform pattern 4 had a significantly increased chance of being found to have no OCD at the time of RP. There were no clinical or pathologic parameters at the time of TRUS-guided biopsy that identified risk factors for Gleason score upgrading at RP in this study. Cribriform morphology detected on biopsy in patients with Gleason score 3 + 4 = 7 PCa is associated with tumour upstaging after RP and may be considered a contraindication to active surveillance.

Identification of pathologically favorable disease in intermediate-risk prostate cancer patients: Implications for active surveillance candidates selection.

Intermediate-risk prostate cancer (PCa) represents a heterogeneous disease, where a non-negligible proportion of patients harbor favorable pathologic characteristics and are potentially eligible for active surveillance (AS). We aimed at developing a model for the identification of pathologically favorable PCa at radical prostatectomy (RP) among intermediate-risk patients. Overall, 3,821 intermediate-risk patients treated with RP at two centers between 2005 and 2013 were identified. Pathologically favorable PCa was defined as low-grade organ-confined disease. Age, biopsy Gleason, PSA density (PSAD), and the percentage of positive cores were included in multivariable logistic regression analyses predicting favorable PCa and formed the basis for a logistic regression-based risk calculator. The internally validated discrimination and calibration of the risk calculator were quantified using 200 bootstrap resamples. Decision curve analysis (DCA) provided an estimate of the net benefit obtained using this model versus treating no one and treating everyone. Overall, 10.0% of all intermediate risk patients had favorable disease. In multivariable analyses, patients with biopsy Gleason score ≤6 had higher probability of favorable disease compared to those with higher-grade disease (P < 0.001). Similarly, age, PSAD, and percentage of positive cores were associated with the probability of favorable disease (all P ≤ 0.01). The risk calculator achieved a validated accuracy of 82.5%. The DCA showed that our prediction model is better than both treating no one and treating everyone. One out of ten intermediate-risk patients harbors favorable disease at RP. Our novel, pre-operative, validated risk calculator may help clinicians identifying patients who could be considered for conservative therapy approaches such as AS.

Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: Results from a prospective single-center study

BackgroundThe aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP). MethodsThe study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen≥0.2ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index. ResultsMean total prostate-specific antigen and mean PHI levels were 5.76ng/ml (interquartile range: 4.2–8.7) and 46.0 (35–62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were. ConclusionsPreoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed.

Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with 103Pd? Results of two prospective randomized trials.

To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients. Trial 44/20 randomized patients to 44Gy plus 90Gy (103)Pd vs. 20Gy with 115Gy (103)Pd, and the subsequent trial randomized patients to the 20Gy arm vs. 125Gy (103)Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. In 44/20 trial, 13-year BF, prostate cancer-specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02ng/mL. With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort.

Risk based neoadjuvant chemotherapy in muscle invasive bladder cancer.

Muscle invasive bladder cancer (MIBC) is an aggressive disease that frequently requires radical cystectomy (RC) to achieve durable cure rates. Surgery is most effective when performed in organ-confined disease, with the best outcomes for those patients with a pT0 result. The goals of neoadjuvant chemotherapy (NC) are to optimize surgical outcomes for a malignancy with limited adjuvant therapies and a lack of effective salvage treatments. Despite level 1 evidence demonstrating a survival benefit, the utilization of NC has been hampered by several issues, including, the inability to predict responders and the perception that NC may delay curative surgery. In this article, we review the current efforts to identify patients that are most likely to derive a benefit from NC, in order to create a risk-adapted paradigm that reserves NC for those who need it.

Long-term Oncologic Outcomes Following Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BackgroundLong-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) are limited and based largely on single-institution series. ObjectiveReport survival outcomes of patients who underwent RARC ≥5 yr ago. Design, setting, and participantsRetrospective review of the prospectively populated International Robotic Cystectomy Consortium multi-institutional database identified 743 patients with RARC performed ≥5 yr ago. Clinical, pathologic, and survival data at the latest follow-up were collected. Patients with palliative RARC were excluded. Final analysis was performed on 702 patients from 11 institutions in 6 countries. InterventionRARC. Outcome measurements and statistical analysisOutcomes of interest, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were plotted using Kaplan-Meier survival curves. A Cox proportional hazards model was used to identify factors that predicted outcomes. Results and limitationsPathologic organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21% of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18–84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC disease and SMs were associated with poorer RFS, CSS, and OS on multivariable analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs were predictors of RFS (hazard ratio: 3.20 and 2.16; p<0.001 and p<0.005, respectively). Stratified survival curves demonstrated poorer outcomes for positive SM, LN, and non-OC disease. Retrospective interrogation and lack of contemporaneous comparison groups that underwent open radical cystectomy were major limitations. ConclusionsThe largest multi-institutional series to date reported long-term survival outcomes after RARC. Patient summaryPatients who underwent robot-assisted radical cystectomy for bladder cancer have acceptable long-term survival.

The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior

BackgroundThe molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. MethodsThe expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. ResultsMiR-371 underexpression correlated with non–organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5α-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5α-dihydrotestosterone. ConclusionOur data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.

Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma.

We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2-181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper's most important limitations include its retrospective nature and its relatively small number of patients. No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function.

MP67-19 ONCOLOGICAL OUTCOMES OF TOTALLY INTRACORPOREAL ROBOT-ASSISTED RADICAL CYSTECTOMY: RESULTS FROM THE ERUS SCIENTIFIC WORKING GROUP.

ABSTRACT: INTRODUCTION AND OBJECTIVES Data on the oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC) is limited. Globally extracorporeal urinary diversion following RARC remains the most common approach despite potential advantages of a completely minimally invasive approach. We report oncological outcomes and associated prognostic factors from a multi-institutional European database focusing on the centres performing totally intracorporeal RARC. METHODS In the ERUS scientific working group database, 467 patients underwent totally intracorporeal RARC for bladder cancer between 2003 and 2014. Clinical and pathological data at the time of the latest follow-up was reviewed. Recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were the outcomes of interest and evaluated using the Kaplan Meier estimator. Multivariable Cox regression analysis was performed to identify factors associated with outcomes of interest. RESULTS Mean age was 67 years, 80% were men. 384 (82%) patients were alive at the time of the analysis. Median follow-up was 17.9 months (range 1-130 months). 87 patients (19%) had undergone surgery 3 or more years' ago. Median follow-up of patients alive was 16 months. 31% patients had pathological non organ-confined disease. Positive surgical margins were present in 5%; median lymph node yield was 18 with 19% of patients having positive lymph nodes. The 3-year RFS, CSS and OS were 73%, 75% and 73% respectively. On multivariable analysis, non-organ confined disease was found to impact RFS, CSS and OS (HR 4.0, 4.3 and 4.2 respectively) and LN positive disease was associated with poorer RFS (HR 2.1). Histopathology stage pT0 was a positive prognostic indicator associated with better RFS, CSS and OS (HR 0.15, 0.16 and 0.74 respectively). CONCLUSIONS This is the largest reported multi-institutional cohort of totally intracorporeal RARC showing acceptable medium term survival outcomes comparable to open radical cystectomy series. The ERUS scientific working group database indicates that a totally intracorporeal approach is replicable.

MP4-07 IS A THRESHOLD VOLUME OF DISEASE NECESSARY FOR GG3+4=7 PROSTATE CANCER TO METASTASIZE?

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2015MP4-07 IS A THRESHOLD VOLUME OF DISEASE NECESSARY FOR GG3+4=7 PROSTATE CANCER TO METASTASIZE? Christine Murekeyisoni, Kristopher Attwood, Shervin Badkhshan, Kurshid Guru, James Mohler, and Eric Kauffman Christine MurekeyisoniChristine Murekeyisoni More articles by this author , Kristopher AttwoodKristopher Attwood More articles by this author , Shervin BadkhshanShervin Badkhshan More articles by this author , Kurshid GuruKurshid Guru More articles by this author , James MohlerJames Mohler More articles by this author , and Eric KauffmanEric Kauffman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.150AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Treatment is typically recommended for Gleason grade (GG) 7 prostate cancer due to concern for metastasis, however only a small subset of GG3+4=7 cancers harbor metastatic potential and overtreatment is common. Clinicopathologic features of GG3+4 cancers which reliably predict metastasis would be helpful but are presently unknown. Here we test the hypothesis that a threshold volume of GG3+4 disease is necessary for metastasis. METHODS Medical records of 585 consecutive prostate cancer patients undergoing radical prostatectomy at Roswell Park Cancer Institute with GG3+4 final pathology and >1 year of follow up were reviewed. Clinicopathologic variables were tested for association with metastasis using Fisher's Exact and T-test analyses, including tumor volume expressed as percentage of the prostate gland. RESULTS Median PSA of GG3+4 prostatectomy patients was 5.5ng/dL. Most GG3+4 cancers (394, 67%) had pT2 stage, while 173 (30%) and 18 (3%) had pT3 and pT4 stage, respectively. Median GG3+4 tumor volume was 15% of the prostate. At a median follow up of 59 months, 15% of GG3+4 patients had biochemical failure, including 9 cases (2%) of metastasis. Metastasis occurred in 0% (0/304) of patients with prostatectomy tumor volume <20%, but 3% (9/281) of patients with tumor volume ≥20% (p=0.0013, Figure 1). Similarly, metastasis occurred in 0% (0/394) of patients with pT2 stage, but 5% (9/191) of patients with pT3/T4 stage (p<0.0001, Figure 1). Hence, all metastatic cases were associated with bulky prostatectomy pathology, and either pT2 stage or tumor volume <20% was 100% accurate for predicting freedom from metastasis. Metastasis was not associated with margin status (p=0.70) or PSA (p=0.086). CONCLUSIONS Low volume (<20% of the prostate), organ-confined disease appears to identify a subset of GG3+4 patients lacking metastatic potential. A threshold bulk of disease may be necessary for Gleason grade 3+4 prostate cancer to metastasize, supporting the related idea that a limited pattern 4 grade may be insufficient for metastasis. These findings have implications for less stringent follow up in GG3+4 patients after prostatectomy, and for continued investigation of active surveillance as a first-line option in patients with low volume GG3+4 on biopsy. Validation in additional GG3+4 cohorts will be valuable. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAl-Tartir T, Murekeyisoni C, Attwood K, Badkhshan S, Mehedint D, Safwat M, Guru K, Mohler J and Kauffman E (2018) Outcomes of Scheduled vs For-Cause Biopsy Regimens for Prostate Cancer Active SurveillanceJournal of Urology, VOL. 196, NO. 4, (1061-1068), Online publication date: 1-Oct-2016. Volume 193Issue 4SApril 2015Page: e29 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christine Murekeyisoni More articles by this author Kristopher Attwood More articles by this author Shervin Badkhshan More articles by this author Kurshid Guru More articles by this author James Mohler More articles by this author Eric Kauffman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP4-17 PATHOLOGIC GLEASON 8-10: DO ALL MEN DO POORLY? RESULTS FROM THE SEARCH DATABASE

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2015MP4-17 PATHOLOGIC GLEASON 8-10: DO ALL MEN DO POORLY? RESULTS FROM THE SEARCH DATABASE Sean Fischer, Ross Simon, Lauren Howard, William Aronson, Martha Terris, Christopher Kane, Christopher Amling, Matt Cooperberg, Stephen Freedland, and Adriana Vidal Sean FischerSean Fischer More articles by this author , Ross SimonRoss Simon More articles by this author , Lauren HowardLauren Howard More articles by this author , William AronsonWilliam Aronson More articles by this author , Martha TerrisMartha Terris More articles by this author , Christopher KaneChristopher Kane More articles by this author , Christopher AmlingChristopher Amling More articles by this author , Matt CooperbergMatt Cooperberg More articles by this author , Stephen FreedlandStephen Freedland More articles by this author , and Adriana VidalAdriana Vidal More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.160AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pathologic Gleason 8–10 is associated with high risk of biochemical recurrence (BCR). However, whether there are subsets of men with Gleason 8–10 who have particularly high or low BCR risk is unknown. We examined predictors for early BCR (2-years) after radical prostatectomy (RP), among patients with pathological Gleason 8–10. METHODS We identified 459 patients treated with RP with pathologic Gleason 8–10 in the SEARCH database. Patients were stratified into 5 groups based on pathological characteristics – Group 1: men with negative surgical margins and no extracapsular extension (-SM/-ECE), Group 2 (+SM/-ECE), Group 3 (-SM/+ECE), Group 4 (+SM/+ECE), and Group 5: men with seminal vesicle invasion (+SVI). BCR was defined as a single PSA greater than 0.2 ng/ml, 2 values of 0.2 ng/ml, or secondary treatment for an elevated postoperative PSA. Cox proportional hazard models were used to compare early BCR (2-years post-RP) among groups and a log-rank test was used to assess the difference between survival curves by group. RESULTS At 2-years post-RP, patients in Group 5 (+SVI) had the highest BCR risk (66%) whereas men in Group 1 (-SM/-ECE) had the lowest risk (14%, p<0.001). No significant difference in recurrence among groups 2 to 4 (∼50% recurrence, log-rank, p=0.28) was found. On multivariable analysis after adjusting for PSA, age, pathological Gleason sum, and clinical stage; Group 5 had the highest recurrence risk, Groups 2–4 were at intermediate-risk with no differences among the groups, and Group 1 had the lowest risk of recurrence. CONCLUSIONS In patients with high grade (Gleason 8–10) prostate cancer after RP, the presence of surgical margins, extracapsular extension, both surgical margins and extracapsular extension, and seminal vesicle invasion are all associated with an increased risk of early BCR. While patients with seminal vesicle invasion are at the highest risk of recurrence, the presence of any of these pathological features among patients with Gleason 8–10 may warrant adjuvant radiation. On the contrary, men with organ-confined margin negative disease have a very low risk of early BCR despite Gleason 8–10 disease. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e33 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sean Fischer More articles by this author Ross Simon More articles by this author Lauren Howard More articles by this author William Aronson More articles by this author Martha Terris More articles by this author Christopher Kane More articles by this author Christopher Amling More articles by this author Matt Cooperberg More articles by this author Stephen Freedland More articles by this author Adriana Vidal More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP17-14 UTILITY OF PREOPERATIVE 3 TESLA MULTIPARAMETRIC PELVIC PHASED-ARRAY MAGNETIC RESONANCE IMAGING IN PREDICTION OF EXTRACAPSULAR EXTENSION OF PROSTATE CANCER AND ITS IMPACT ON SURGICAL MARGIN STATUS: EXPERIENCE AT A CANADIAN TERTIARY ACADEMIC HEALTH CENTER

You have accessJournal of UrologyImaging/Radiology: Uroradiology III1 Apr 2015MP17-14 UTILITY OF PREOPERATIVE 3 TESLA MULTIPARAMETRIC PELVIC PHASED-ARRAY MAGNETIC RESONANCE IMAGING IN PREDICTION OF EXTRACAPSULAR EXTENSION OF PROSTATE CANCER AND ITS IMPACT ON SURGICAL MARGIN STATUS: EXPERIENCE AT A CANADIAN TERTIARY ACADEMIC HEALTH CENTER Jen Hoogenes, Ian Wright, Colm Boylan, and Bobby Shayegan Jen HoogenesJen Hoogenes More articles by this author , Ian WrightIan Wright More articles by this author , Colm BoylanColm Boylan More articles by this author , and Bobby ShayeganBobby Shayegan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.856AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Magnetic resonance imaging (MRI) is rapidly gaining ground in the preoperative planning for radical prostatectomy (RP). Reports of its predictive ability to detect extracapsular extension (ECE) have varied significantly in the literature. We evaluated the ability of 3 Tesla (3T) pelvic phased-array (PPA) multiparametric MRI (mpMRI) to predict ECE and its subsequent effect on surgical margin status in a patient cohort treated by a single urologic oncologist. METHODS We retrospectively evaluated 48 preoperative RP patients who underwent 3T PPA mpMRI based on clinical probability of adverse pathological features. T1- and T2-weighted sequences, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) mpMRI was used in all cases, each read by an expert genitourinary radiologist. Tumor stage based on mpMRI was compared to pathological stage. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting ECE were calculated. Positive surgical margin rates of patients with positive ECE on mpMRI were compared to those patients with negative ECE on mpMRI. RESULTS Forty-two (88%) patients were intermediate or high risk based on D'Amico criteria. The mpMRI reports predicted 19 (40%) patients to be positive for ECE, while final pathology revealed that nine of these patients were actually ECE positive, with two having positive surgical margins. Of the 29 (60%) patients who were not predicted to have ECE based on mpMRI, 14 had positive ECE on pathology, 12 of whom had positive surgical margins. Preoperative 3T PPA mpMRI using T1- and T2-weighted sequences with DWI and DCE achieved a sensitivity of only 44% and a specificity of 61% in predicting ECE on surgical pathology. The PPV and NPV were 55% and 50%, respectively. Of the patients with ECE reported on mpMRI, 11% had positive surgical margins compared to 41% of those patients without ECE on mpMRI. CONCLUSIONS At our center, the use of preoperative 3T PPA mpMRI using T1- and T2-weighted sequences with DWI and DCE in predicting pathological ECE and surgical margin status is of questionable benefit. Our findings suggest that preoperative mpMRI reports of organ-confined disease may result in closer surgical dissection and subsequent positive surgical margins, regardless of true pathological staging. As such, caution should be exercised when basing intraoperative decisions on mpMRI findings. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e181 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jen Hoogenes More articles by this author Ian Wright More articles by this author Colm Boylan More articles by this author Bobby Shayegan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Organ-sparing surgery in urology: partial cystectomy.

While radical cystectomy continues to be the gold standard for surgical management of muscle invasive bladder cancer, there has been a renewed interest in partial cystectomy as a viable treatment alternative. The purpose of this review is to summarize and discuss the recent literature regarding partial cystectomy for bladder cancer. Utilization of partial cystectomy has remained stable, at a rate of 7-10% of all cystectomies performed nationally. Additionally, recent population-based series as well as single institution cohorts have found that partial cystectomy did not compromise survival when compared to radical cystectomy. While patients may recur, those with organ-confined disease had no difference in survival following salvage cystectomy when compared to primary radical cystectomy. Current data indicate 14% of patients experience an in-hospital complication, which is a marked decrease compared to radical cystectomy. Finally, innovations in surgical technique, such as robotics, as well as the inclusion of partial cystectomy into trimodal therapy, offer exciting new frontiers in bladder cancer treatment. Once maligned, partial cystectomy now represents a standard-of-care option for management of bladder cancer. Although additional research is needed to clarify patient selection and outcomes, partial cystectomy is an important treatment option for appropriately selected patients.

Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity.

Rates of late toxicity are higher for salvage treatment of local recurrence after prior radiotherapy. We present our experience with salvage prostate brachytherapy (BT) for local recurrence after definitive external beam radiotherapy with attention to the relationship between dose and late toxicity. From 2005 to 2012, 18 patients with biopsy proven locally recurrent prostate cancer and negative staging received low-dose-rate BT with a prescribed dose of 130-144Gy. Toxicities were graded using Common Terminology Criteria for Adverse Events, version 3.0. Median followup is 31.5months (range, 12-104). International Prostate Symptom Scores peaked at 3months (median, 21/35), returning to baseline by 24months. Urinary catheterization rate was 33% (median duration, 14days; range, 1-90days). Late Grade 3/4 genitourinary toxicity occurred in 1 patient each, one of whom also had Grade 3 late gastrointestinal toxicity; urethral strictures developed in three others. These 5 patients with late toxicity had higher dose to the prostate (isodose enclosing 90% [D90] median, 151 Gy; range, 135-185 Gy) compared with those without late complications (median, 134Gy; range, 105-165; p < 0.04). Acute gastrointestinal toxicity Grade <3 occurred in 44%. Four patients (22%) experienced biochemical failure. Salvage low-dose-rate prostate BT can provide durable biochemical control. Care should be taken to select patients with higher likelihood of organ-confined disease. The goal of planning should be to treat the recurrent disease to an adequate dose with careful attention to maintain a conservative D90.

What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series

BackgroundThe risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP). Materials and methodsOverall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non–organ-confined disease, Gleason score ≥4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA)≥0.2ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics. ResultsOverall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density≥10ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001). ConclusionsAmong patients eligible for AS treated with RP, only men with Gleason score≥4+3 or non–organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.

Presence of Concomitant Non-muscle-invasive Bladder Cancer in Chinese Patients with Upper Tract Urothelial Carcinoma: Risk Factors, Characteristics, and Predictive Value.

To explore the characteristics, predictive risk factors, and prognostic effect of concomitant non-muscle-invasive bladder cancer (NMIBC) in patients with upper tract urothelial carcinoma (UTUC). We evaluated 727 consecutive UTUC patients treated with radical resection between 2000 and 2012 in a high-volume center of China. Preoperative cystoscopy was performed in all patients. Patients with previous or concomitant total cystectomy were excluded. Overall, 73 patients (10.0%) had NMIBC. Concomitant NMIBC was associated with previous bladder cancer (p=0.003), tumor located in ureter (p=0.008), multifocality (p<0.001), and preoperative renal insufficiency (p=0.023). The presence of concomitant NMIBC was predictive for lower tumor stage (p=0.019), papillary architecture (p=0.023), and organ-confined disease (pT<3 and N-, p=0.006). The median follow-up duration was 57months. The presence of concomitant NMIBC was a risk factor for bladder recurrence (p<0.001), and particularly in patients with non-muscle-invasive UTUCs, it affects cancer-specific survival (odds ratio 1.614, p=0.030) and contralateral recurrence (odds ratio, 1.907, p=0.016). Most concomitant NMIBC were found at the lateral wall or bladder neck, while most intravesical recurrences occurred near the site of surgery or posterior wall. The most common site for concomitant NMIBC was lateral wall and bladder neck, and previous bladder cancer, tumor located in ureter, tumor multifocality, and preoperative renal insufficiency were risk factors for concomitant NMIBC. The presence of concomitant NMIBC is predictive for relative better pathologic outcomes but higher rate of bladder recurrence, while the effect on postoperative survival was limited with patients early-stage UTUCs. The potential mechanisms need further investigation.

Abstract A63: A stroma-based 15 gene profile for prostate cancer suggests increased DNA methylation and senescence in the stroma of patients with poor prognosis

Abstract Biomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. Barriers to biomarker discover include the polyclonal/multifocal nature of prostate tumors and the cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment) is much less affected by these problems but exhibit hundreds of gene expression changes compared to normal stroma (1). We performed Affymetrix gene expression profiles of tumor-adjacent stroma for asymptomatic organ-confined disease with negative surgical margins. We identified a set of 115 probe sets for which the expression levels were significantly correlated with time-to-relapse following prostatectomy. Next, we compared expression in patients that chemically relapsed shortly after prostatectomy (&amp;lt; 1 year) versus patients that did not relapse in the first four years after prostatectomy. This comparison yielded 131 differentially expressed microarray probe sets. 19 probe sets (15 genes) were common between the two approaches, a significant degree of overlap (p &amp;lt; 0.0001). Using these 19 probe sets as input, we developed a PAM (Predicative Analysis of Microarrays)-based classifier by training on the expression profiles of samples containing stroma near tumor; 9 rapid relapse patient samples and 9 indolent patient samples. We then tested (validated) the classifier on array data from 47 independent samples containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. Notably of the 19 probe sets, 15 are down-regulated in poor outcome disease. Moreover of the 4 upregulated probe sets in poor outcome disease are transcripts of p53 (2) and its target genes, p21 and GADD45A. These features suggest an increased proportion of senescent cells with increased gene silencing (2,3) in the stroma, consistent with a substantially increased stressful environment in the tumor-adjacent microenvironment of of the subset of prostate cancers with poor outcome. 1. Jia, . et al. Canc. Res. 2011;71 :2476-2487. 2. Gabai, V. et al. Oncogene. 2010 ;2129 :1952-1962. 3. Banerjee, J. et al. Oncogene 2013 ; Epub., PMC accession no. 24141771. Citation Format: Zhenyu Jia, Farah Rahmatpanah, Xin Chen, Waldemar Lernhardt, Yipeng Wang, Xiao-Qin Xia, Anne Sawyers, Michael McClelland, Dan Mercola. A stroma-based 15 gene profile for prostate cancer suggests increased DNA methylation and senescence in the stroma of patients with poor prognosis. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A63. doi:10.1158/1538-7445.CHTME14-A63

Results and Outcomes of Radical Prostatectomy for Low-Risk Prostate Cancer in North African Ethnic Group

Background: Prostate cancer (PCa) is a leading cause of cancer death in the world. Indeed, its incidence is increasing with diagnoses made increasingly early thanks to the introduction of screening by prostate-specific antigen (PSA). This detection is done with most often localized stages, causes over diagnosis whose main consequence is overtreatment of the low-risk cancers that would have evolved very slowly and not aggressively without any treatment. Methods: To evaluate the pattern of treatment decisions and oncological outcomes among men aged ? 60 and ? 70 years with low-risk PCa in North African ethnic group, we examined the proportion and outcomes of men with low-risk disease treated with radical prostatectomy (RP) at our institution in the last decade. Results: Median age of the 166 men in the study cohort was 66 years. Mean serum PSA at diagnosis was 5.9 ng/mL with an average ratio of 13.77%. At diagnosis, 70.3% of our patients were symptomatic with lower urinary tract symptom (LUTS) with a suspicious digital rectal examination in 9.7% of cases. Clinical stage was T1a/b in 5.1%, T1c in 79.6% and T2a in 15.3% of the patients. All men had Gleason score (GS) 6 PCa on biopsy and all men were treated with open radical retropubic prostatectomy. Except for age, there was no difference in the clinical features of men aged 65 - 69 and ? 70 years. One hundred percent of cancers are adenocarcinomas. Final pathological review revealed organ-confined disease in 77.1% of the men, extracapsular extension (ECE) in 22%, seminal vesicle invasion (SVI) in 8.6% and lymph node involvement in 3.2%. Conclusion: The challenge lies in identifying the aggressiveness of the cancer at diagnosis, and the ability to predict the individual risk of progression, active surveillance (AS) strategy needs to be validated by long-term results, new therapy options are currently being evaluated, and we consider that RP is an adequate therapy in men with low risk of d’Amico features. World J Nephrol Urol. 2015;4(4):251-255 doi: http://dx.doi.org/10.14740/wjnu241w

Urothelial carcinoma in bladder diverticula: outcomes after radical cystectomy.

To characterize the clinical and pathologic staging of patients with urothelial carcinoma (UC) in bladder diverticula (BD) after undergoing radical cystectomy (RC) and determine the impact of UCBD on recurrence and survival. We reviewed our institutional database of patients who underwent RC for UC (1971-2009). Outcomes were compared between patients with and without UCBD. Kaplan-Meier curves estimated recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox regression evaluated associations between UCBD and survival. Inclusion criteria were met in 1991 patients. UCBD was seen in 77 (4 %) patients and occurred exclusively in men (mean age 68 ± 8.5 years). The highest pathologic stage tumor was found in the BD in 44 (57 %) of these patients. Pathologic upstaging was more common with UCBD compared with UC not in BD (48 vs. 39 %, p = 0.031). On univariate analysis, no differences in RFS or OS were observed comparing patients with or without UCBD stratified by clinically organ-confined (≤T2) and extravesical (>T2) disease. On multivariable analysis, the presence of UCBD was not associated with differences in RFS (HR 0.92, 95 % CI 0.59-1.42, p = 0.69) or OS (HR 0.98, 95 % CI 0.74-1.31, p = 0.92). Upstaging was common in patients with UCBD, observed in almost half of the patients. There were no differences in RFS or OS after RC when comparing patients with or without UC in a diverticulum stratified by stage.

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?

To evaluate if cumulative prostate cancer length (CCL) on prostate needle biopsy divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer on radical prostatectomy (RP) in patients with prostate cancer eligible for active surveillance (AS). Patients diagnosed with prostate cancer on extended (≥10 cores) biopsy with an initial prostate-specific antigen (iPSA) level of <15 ng/mL, clinical stage (cT) ≤ 2a, and highest biopsy Gleason score 3 + 3 = 6 or 3 + 4 = 7 with <3 positive cores who underwent RP were included in the study. The CCL/core and presence of insignificant cancer (organ-confined, volume <0.5 mL, Gleason score at RP ≤6) were recorded. pT2 prostate cancer with RP Gleason score ≤3 + 4 = 7 and volume <0.5 mL were categorised as low-tumour-volume organ-confined disease (LV-OCD). In all, 221 patients met the inclusion criteria: the mean age was 59 years and the median iPSA level was 4.5 ng/mL. The clinical stage was cT1 in 86% of patients; biopsy Gleason score was 3 + 3 = 6 in 67% (group 1) and 3 + 4 = 7 in 33% of patients (group 2). The maximum percentage of biopsy core involvement was <50 in 85%; the median CCL/core was 0.15 mm. Insignificant cancer was found in 27% and LV-OCD in 44% of patients. Group 2 was associated with higher number of positive cores, maximum percentage core involvement, total prostate cancer length, and CCL/core. Group 1 was more likely to have insignificant cancer (39%) or LV-OCD (54%) than group 2 (3% and 23%, respectively). Group 2 had significantly higher RP Gleason score and pathological stage. Univariate analysis of group 1 showed that the iPSA level, maximum percentage core involvement, prostate cancer length, and CCL/core were all significantly associated with insignificant cancer and LV-OCD. For group 2, the number of positive cores (1 vs 2) was also significantly associated with LV-OCD. On multivariate logistic regression analysis, maximum percentage core involvement of <50, and number of positive cores (1 vs 2) were independent predictors of insignificant cancer in group 1; biopsy Gleason score, maximum percentage core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were all independent predictors of LV-OCD in the whole population. The maximum percentage of core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were also independent predictors of LV-OCD in group 1 patients. In patients eligible for AS, a CCL/core of <0.20 mm was significantly associated with insignificant cancer and LV-OCD. However, when parameters of cancer burden were considered, CCL/core did not independently add any additional value for predicting insignificant cancer in patients with biopsy Gleason score 6. The CCL/core was an independent predictor of LV-OCD in the whole population and in group 1 patients, although the model including prostate cancer length showed slightly higher area under the receiver operating characteristic curve.