Clinical Stage T1c Research Articles

Impact of Prostate Weight on Probability of Positive Surgical Margins in Patients With Low-risk Prostate Cancer After Robotic-assisted Laparoscopic Radical Prostatectomy

To evaluate the impact of prostate weight (PW) on probability of positive surgical margin (PSM) in patients undergoing robotic-assisted radical prostatectomy (RARP) for low-risk prostate cancer. The cohort consisted of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6) who underwent RARP with bilateral nerve-sparing at our institution by 1 of 2 surgeons from 2003 to 2009. PW was obtained from the pathologic specimen. The association between probability of PSM and PW was assessed with univariate and multivariate logistic regression analysis. A PSM was identified in 105 patients (15.2%). Patients with PSM had significant higher prostate-specific antigen (P = .04), smaller prostates (P = .0001), higher Gleason score (P = .004), and higher pathologic stage (P < .0001). After logistic regression, we found a significant inverse relation between PSM and PW (OR 0.97%; 95% confidence interval [CI] 0.96, 0.99; P = .0003) in univariate analysis. This remained significant in the multivariate model (OR 0.98%; 95% CI 0.96, 0.99; P = .006) adjusting for age, body mass index, surgeon experience, pathologic Gleason score, and pathologic stage. In this multivariate model, the predicted probability of PSM for 25-, 50-, 100-, and 150-g prostates were 22% (95% CI 16%, 30%), 13% (95% CI 11%, 16%), 5% (95% CI 1%, 8%), and 1% (95% CI 0%, 3%), respectively. Lower PW is independently associated with higher probability of PSM in low-risk patients undergoing RARP with bilateral nerve-sparing.

Clinical characteristics and pathologic findings in patients eligible for active surveillance who underwent radical prostatectomy

ObjectiveTo analyze clinical characteristics and pathologic findings in patients eligible for active surveillance (AS) who underwent radical prostatectomy (RP). Materials and methodsWe collected data from 495 patients who underwent RP during an 8-year period. We have then selected those who would have been eligible for AS according to 2 different sets of published criteria. Group 1 used broader criteria: clinical stage ≤ T2b, Gleason score of seven or less and PSA ≤ 15 ng/ml. Group 2 used more restrictive criteria: age < 75 years, PSA < 10 ng/ml, clinical stage T1c or T2a, Gleason score of 6 or less, at least 10 biopsies available and a tumor length of less than 3 mm in 2 biopsy cores. ResultsOverall, 207 patients (41.8%) were included in group 1 and 43 (8.7%) in group 2. The median follow-up was 31 (3–108) and 32 (3–84) months in groups 1 and 2, respectively. We recorded 132 cases (63.8%) of pT2c in group 1 and 31 in group 2 (72.1%). Extracapsular extension was noted in 37 (17.9%) and 2 (4.7%) specimens from groups 1 and 2, respectively. In groups 1 and 2, a biochemical failure occurred in 47 patients (22.7%) and 6 (14%), respectively. The Gleason score at biopsy was underestimated in 54 (26%) and 9 (21%) of patients in groups 1 and 2, respectively. ConclusionOverall, 21% to 26% of patients eligible for AS had upgraded Gleason scores at prostatectomy and actually had a more significant disease with a potentially aggressive behavior. Therefore, based on criteria, certain tumors currently selected for AS may be significant and may require radical treatment.

Prediction of patient‐specific risk and percentile cohort risk of pathological stage outcome using continuous prostate‐specific antigen measurement, clinical stage and biopsy Gleason score

• To develop a '2010 Partin Nomogram' with total prostate-specific antigen (tPSA) as a continuous biomarker, in light of the fact that the current 2007 Partin Tables restrict the application of tPSA as a non-continuous biomarker by creating 'groups' for risk stratification with tPSA levels (ng/mL) of 0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0 and >10.0. • To use a 'predictiveness curve' to calculate the percentile risk of a patient among the cohort. • In all, 5730 and 1646 patients were treated with radical prostatectomy (without neoadjuvant therapy) between 2000 and 2005 at the Johns Hopkins Hospital (JHH) and University Clinic Hamburg-Eppendorf (UCHE), respectively. • Multinomial logistic regression analysis was performed to create a model for predicting the risk of the four non-ordered pathological stages, i.e. organ-confined disease (OC), extraprostatic extension (EPE), and seminal vesicle (SV+) and lymph node (LN+) involvement. • Patient-specific risk was modelled as a function of the B-spline basis of tPSA (with knots at the first, second and third quartiles), clinical stage (T1c, T2a, and T2b/T2c) and biopsy Gleason score (5-6, 3 + 4 = 7, 4 + 3 = 7, 8-10). • The '2010 Partin Nomogram' calculates patient-specific absolute risk for all four pathological outcomes (OC, EPE, SV+, LN+) given a patient's preoperative clinical stage, tPSA and biopsy Gleason score. • While having similar performance in terms of calibration and discriminatory power, this new model provides a more accurate prediction of patients' pathological stage than the 2007 Partin Tables model. • The use of 'predictiveness curves' has also made it possible to obtain the percentile risk of a patient among the cohort and to gauge the impact of risk thresholds for making decisions regarding radical prostatectomy. • The '2010 Partin Nomogram' using tPSA as a continuous biomarker together with the corresponding 'predictiveness curve' will help clinicians and patients to make improved treatment decisions.

Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a “normal” prostate specific antigen and digital rectal examination

Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a "normal" PSA (<4 ng/ml) and non-suspicious digital rectal examination (DRE) remains to be determined. We examined 203 men of European ancestry with clinical stage T1c CaP diagnosed at a "normal" PSA and 611 healthy volunteer controls. The genotypes for 17 different risk alleles were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and non-carriers (defined using best-fit genetic model) of these variants. All risk alleles were present at an increased frequency in cases with "normal" PSA values and DRE compared to controls. Amongst CaP patients, carriers of an increasing number of genetic risk factors (i.e., alleles and positive family history) were at a significantly increased risk of CaP (P-trend <0.001). Specifically, men with >10 genetic risk factors had an 11.2-fold risk (95% CI 4.3-29.2) of having the disease compared to men with ≤5 variants. There also was a higher frequency of many the variants amongst men with adverse pathologic features. A substantial proportion of biopsy-detectable CaP occurs in men with "normal" PSA levels and negative DRE. In this population, CaP risk alleles and family history are significantly associated with CaP risk and may help predict aggressive disease. Future studies are warranted to determine the utility of incorporating these variants into CaP screening programs.

An unusual case of radioactive seed migration to the vertebral venous plexus and renal artery with nerve root compromise

Purpose We report a case of prostate brachytherapy seed migration to the vertebral venous plexus and subsequently to the renal artery with corresponding dosimetry analysis describing nerve doses. Methods and Materials A 52-year-old male with low-risk prostate carcinoma (clinical stage T1c; Gleason score = 6; prostate-specific antigen level of 5.5) underwent transperineal permanent prostate seed implant. Postimplantation routine imaging had failed to locate the missing seed, but he subsequently presented with back pain and parathesia with radiation down the leg. Results CT with bony windows and MRI had located the seed in the left L5 vertebral venous plexus. Neurosurgical intervention failed to locate and remove the migrated seed. Postsurgery, the left lower limb parathesia persisted but had normal nerve conduction studies. Dose to the spinal nerve roots and nearby structures were estimated using a GEANT4 Monte Carlo simulation. Serial X-ray imaging and CT had found that the seed had further migrated to left renal hilum. Conclusions Seed migration to vertebral venous plexus is uncommon and to our knowledge this is the third reported case. Its subsequent migration to the renal hilum is most unusual. CT with bony windows or MRI are required if this is suspected. There is risk of spinal or nerve root damage and dose to these structures has to be estimated using GEANT4, although the tissue tolerance in the setting of low-dose rates are unknown and long-term followup of this patient is required.

Normalization of prostate specific antigen in patients treated with intensity modulated radiotherapy for clinically localized prostate cancer

BackgroundThe purpose of this study was to determine the expected time to prostate specific antigen (PSA) normalization with or without neoadjuvant androgen deprivation (NAAD) therapy after treatment with intensity modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer.MethodsA retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging) treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p < 0.05.ResultsFifty-six of the 133 patients received NAAD (42.1%). Thirty-one patients (23.8%) received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%). The times to serum PSA normalization < 2 ng/mL when treated with or without NAAD were 298 ± 24 and 302 ± 33 days (mean ± SEM), respectively (p > 0.05), and 303 ± 24 and 405 ± 46 days, respectively, for PSA < 1 ng/mL (p < 0.05). Stage T1 and T2 tumors had significantly increased time to PSA normalization < 1 ng/mL in comparison to Stage T3 tumors. Also, higher Gleason scores were significantly correlated with a faster time to PSA normalization < 1 ng/mL.ConclusionsUse of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA < 1 ng/mL in patients with clinically localized prostate cancer.

Total androgen-receptor gene expression inhibitor therapy (TARGET): A phase II trial of neoadjuvant SAHA (S) followed prostatectomy for patients (pts) with high-risk prostate cancer (pc).

e15133 Background: Androgen depletion (ADT) with a gonadotropin releasing hormone (GnRH) analog alone or with an anti- androgen does not ensure complete inhibition of signaling through the androgen receptor (AR). ADT with S (SAHA, suberoylanilide hydroxamic acid), an HDAC, can inhibit HSP90 resulting in loss of HSP90 binding to and degradation of client protein. HDAC inhibitors may reduce AR expression and sensitize pc cells to hormone antagonists. This phase II trial explores whether neoadjuvant ADT with S, can affect signaling through AR, increase the rate of pathologic response (p0), and determine the molecular pathways of response/resistance in pre/posttreatment blood and tissue, respectively, along with testosterone (T), its precursors, and AR target genes. Methods: Pts with newly diagnosed pc of any Gleason score were enrolled as long as they had an abnormal PSA and 1 of 3 or more cores containing ≥ 30% pc. Sixteen of 19 pts were accrued; 11 at MSKCC are reported. Each received S 400mg po daily for 6-8 weeks, bicalutamide 50mg for 4 weeks, and monthly GnRH followed by radical, laparoscopic or robotic prostatectomy. Results: Pretreatment median age was 64yrs, clinical stage T1c 6 pts [T1c-T3], Gleason score 3+4 [7-9], T 343ng/dl [140-521], and PSA 6.36ng/ml [3.87-27.64]. S was well-tolerated; 7 of 11 pts had grade 1 fatigue; 5 had grade 1 diarrhea. Post-surgical median pathologic stage was T2b (5 pts) [1-pT2+; 1-T2c; 2-T3a; 1-T3b; 1-T3bN1]. No pt achieved p0 but 10 of 11 pts achieved a PSA of <0.05 post T recovery with median durability of 87 days [17-379]. Post surgical median time to T recovery in 7 completed pts was 65.1 days [48-167]. Conclusions: The use of neoadjuvant S and a GnRH agonist as proof of concept did not result in a p0 in any of the 11 patients treated to date, however 10 pts had post surgical PSA nadirs of ≤ 0.05 which have been durable. Six additional pts are under treatment at this time. The impact on molecular and biologic markers within postsurgical tissue samples is ongoing. Supported by The Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium, and NCI P50-CA92629 SPORE in Prostate Cancer. No significant financial relationships to disclose.

Active Surveillance for Early-Stage Prostate Cancer: Defining the Triggers for Intervention

Active Surveillance for Early-Stage Prostate Cancer: Defining the Triggers for Intervention

Outcomes After Radical Prostatectomy Among Men Who Are Candidates for Active Surveillance: Results From the SEARCH Database

We sought to evaluate outcomes after radical prostatectomy among men with low-risk prostate cancer who would be candidates for active surveillance. Using the Shared Equal Access Regional Cancer Hospital (SEARCH) database of men treated with radical prostatectomy at multiple equal-access medical centers between 1988 and 2007, 398 of 2062 men (19%) met our criteria for potential active surveillance: clinical stage T1c or T2a, prostate-specific antigen (PSA) <10 ng/mL, Gleason sum ≤6, and no more than 1 or 2 positive cores on at least a sextant biopsy. We examined the risk of adverse pathology, biochemical progression, and PSA doubling time (PSADT) at the time of recurrence. We used a Cox proportional hazards model to determine the significant predictors of PSA progression. Of the men with low-risk prostate cancer, 85% had organ-confined disease, only 2% had seminal vesicle invasion, and no patient had lymph node metastasis. The 5- and 10 year PSA-free survival rates were 81% (95% CI: 76-86%) and 66% (95% CI: 54-76%). On multivariate analysis, older age (P = .005), Agent Orange exposure (P = .02), and obesity (P = .03) were all significantly associated with biochemical failure. Mean and median PSADT among men who experienced recurrence were 37 and 20 months. Only 3 patients experienced recurrence with PSADT < 9 months. Most men with low-risk prostate cancer treated with radical prostatectomy experience long-term PSA control. Those who did experience recurrence often did so with a long PSADT. Consistent with prior SEARCH database reports, older age, Agent Orange exposure, and obesity increased the risk of recurrence.

932 THERE IS NO WAY TO IDENTIFY PATIENTS WHO WILL HARBOR PT2A PROSTATE CANCER AT RADICAL PROSTATECTOMY. IMPLICATIONS FOR FOCAL THERAPIES

You have accessJournal of UrologyProstate Cancer: Localized IV1 Apr 2010932 THERE IS NO WAY TO IDENTIFY PATIENTS WHO WILL HARBOR PT2A PROSTATE CANCER AT RADICAL PROSTATECTOMY. IMPLICATIONS FOR FOCAL THERAPIES Francesco Montorsi, Alberto Briganti, Nazareno Suardi, Umberto Capitanio, Firas Abdollah, Andrea Salonia, Luigi Barbieri, Massimo Freschi, Luca Villa, Giuseppe Zanni, Marco Roscigno, and Patrizio Rigatti Francesco MontorsiFrancesco Montorsi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Firas AbdollahFiras Abdollah More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Luigi BarbieriLuigi Barbieri More articles by this author , Massimo FreschiMassimo Freschi More articles by this author , Luca VillaLuca Villa More articles by this author , Giuseppe ZanniGiuseppe Zanni More articles by this author , Marco RoscignoMarco Roscigno More articles by this author , and Patrizio RigattiPatrizio Rigatti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1748AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Focal therapies represent an emerging therapeutic option for selected patients with low risk prostate cancer. However, low risk patients often harbour multifocal, bilateral disease. The aim of this study was to evaluate the clinical characteristics of patients diagnosed with pT2a prostate cancer at radical prostatectomy (RP). METHODS The study included 3409 patients treated with RP (1988-2009) at a single tertiary referral center. All patients had complete clinical and RP data including number of positive cores and number of total cores taken at biopsy. The clinical characteristics of pT2a patients were compared to 2862 patients with either pathological T2b or T2c disease. Differences in means and proportions were evaluated using the Analysis of Variance (ANOVA) test and Chi-square test, respectively. We identified the most informative cut-off for predicting the presence of pT2a disease for PSA and percentage of positive cores. RESULTS Overall, 547 (16.0%) patients were diagnosed with pT2a prostate cancer at RP. Median PSA at diagnosis in pT2a patients was 6 ng/ml (range 0.4-48.4). Biopsy Gleason sum was 2-6, 7 and 8-10 in 81.9, 12.8 and 5.2%, respectively. Clinical stage was T1c in 68.0, T2: in 29.5 and T3 in 2.5% of pT2a patients, respectively. Median percentage of positive cores in pT2a patients was 17.6 (range: 5.6-100%). When compared to pT2/pTc men, patients with pT2a disease had slightly lower mean PSA value (7.3 vs. 8.4 ng/mL, respectively, p=0.01) and higher rates of biopsy Gleason 6 (81.9% vs. 76.2%, respectively; p=0.001). Mean percentage of positive cores at biopsy was lower in pT2a patients, as compared with pT2b/pT2c (27.9 vs. 40.1%, p<0.001). However, when applying the most significant cut-off for PSA in predicting pT2a (¡Ü4 vs >4), we found that the rate of pT2a was low even in patients with PSA ¡Ü4ng/ml (22.5 % vs 13.8%; p<0.001). Similarly, when patients were stratified according to the most informative cut-off of the percentage of positive cores (<25% vs ¡Ý25%), the rate of pT2a was only 26.5% in those patients with % positive cores <25% (vs 9.6%). Finally, when only patients with PSA ¡Ü4 ng/ml, percentage of positive cores <25%, clinical stage T1c and biopsy Gleason sum ¡Ü6 were considered, only 13.8% of patients harboured a pT2a disease. CONCLUSIONS The clinical characteristics of patients with pT2a at RP are slightly more favourable than patients with pT2b/pT2c disease. The prediction of patients with pT2a is extremely difficult. These results should be taken into account when focal therapies are considered. Milan, Italy© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e363 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Nazareno Suardi More articles by this author Umberto Capitanio More articles by this author Firas Abdollah More articles by this author Andrea Salonia More articles by this author Luigi Barbieri More articles by this author Massimo Freschi More articles by this author Luca Villa More articles by this author Giuseppe Zanni More articles by this author Marco Roscigno More articles by this author Patrizio Rigatti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

V480 FLEXIBLE CO 2 LASER ASSISTED NEUROVASCULAR BUNDLE DISSECTION FOR ROBOTIC PROSTATECTOMY

You have accessJournal of UrologyProstate Oncology1 Apr 2010V480 FLEXIBLE CO2 LASER ASSISTED NEUROVASCULAR BUNDLE DISSECTION FOR ROBOTIC PROSTATECTOMY Philippa Cheetham, Matthew Truesdale, and Ketan Badani Philippa CheethamPhilippa Cheetham More articles by this author , Matthew TruesdaleMatthew Truesdale More articles by this author , and Ketan BadaniKetan Badani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.554AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Carbon dioxide (CO2) lasers have been cited to deliver energy with minimal thermal spread to tissues during dissection. The CO2 laser is thus widely used in head and neck oncology surgery and neurosurgery, resulting in predictable penetration depth and minimal collateral damage. Until recently, use of the CO2 laser as a surgical tool has been limited by the necessity for delivery through a rigid, rather than a fiber-based flexible delivery system. Excess thermal spread during neurovascular bundle (NVB)dissection can affect potency in men following radical prostatectomy. We report on a novel delivery of CO2 laser energy through a flexible fiber to enhance the accuracy of dissection of the NVB during robotic assisted laparoscopic prostatectomy (RALP). METHODS A feasibility study of the OmniGuide® BeamPath™ URO-LG CO2 laser fiber for neurovascular bundle dissection was performed on 8 men with clinical stage T1c, Gleason 6 or 7 prostate cancer during RALP. Upon identification of the NVB, a large needle driver was used to manipulate the fiber. Bilateral lateral fascial nerve sparing was performed in antegrade fashion. RESULTS We evaluated the performance, safety and efficacy of the fiber, which was successfully inserted through the assistant's port (12 mm). The size of the device allowed adequate space for simultaneous insertion of standard 5 mm laparoscopic tools. The fiber was easily manipulated by robotic instruments.Once the pedicles were clipped and dissected, the laser fiber was effective in establishing the plane of dissection between the prostatic capsule and the neurovascular bundle. Visual examination indicated that the thermal footprint of the laser was small, with minimal thermal spread during the nerve sparing portion of the procedure. This resulted in meticulous dissection of the NVB and fascial layer identification.The use of the laser fiber was safe with precise soft tissue cutting, stemming from its ready absorption in water. Whilst the laser did provide extremely accurate dissection, it was unable to serve as an adequate means of coagulation in larger vessels. CONCLUSIONS The flexible CO2 laser fiber was easily manipulated and identification of fascial layers during nerve sparing was facilitated with the fiber. Long-term follow-up is necessary to determine the efficacy of this technology versus conventional techniques on the NVB. Larger studies are currently in progress to determine if use of the flexible CO2 laser fiber results in improvements in functional outcomes with regards to return of sexual potency following robotic prostatectomy. New York, NY© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e189 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Philippa Cheetham More articles by this author Matthew Truesdale More articles by this author Ketan Badani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

659 PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUS ESTRAMUSTINE FOR HIGH RISK PROSTATE CANCER FOLLOWED BY RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2010659 PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUS ESTRAMUSTINE FOR HIGH RISK PROSTATE CANCER FOLLOWED BY RADICAL PROSTATECTOMY Takuya Koie, Teppei Okamoto, Kengo Imanishi, Naoki Sugiyama, Yuichiro Suzuki, Kazuyuki Mori, Shigemasa Kudoh, Takahiro Yoneyama, Yasuhiro Hashimoto, Noritaka Kamimura, and Chikara Ohyama Takuya KoieTakuya Koie More articles by this author , Teppei OkamotoTeppei Okamoto More articles by this author , Kengo ImanishiKengo Imanishi More articles by this author , Naoki SugiyamaNaoki Sugiyama More articles by this author , Yuichiro SuzukiYuichiro Suzuki More articles by this author , Kazuyuki MoriKazuyuki Mori More articles by this author , Shigemasa KudohShigemasa Kudoh More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Noritaka KamimuraNoritaka Kamimura More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1046AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Effective treatment for high risk prostate cancer (PC) has not yet been established. We examined efficacy and safety of neo-adjuvant therapy with LHRH agonist + estramustine (EMP) (LHRH+EMP) followed by retropubic radical prostatectomy (RRP). METHODS Risk stratification was performed according to the D□fAmico□fs method. Eighty seven patients with high risk PC were enrolled onto this trial from September 2005 and August 2009. The LHRH + EMP therapy included administration of LHRH and 280 mg/day EMP for 6 months prior to the RRP. Post-therapy pathological evaluation to no residual disease at RRP (pT0), and PSA-free survival were endpoints of interest. RESULTS The average age of the patients was 67.2 years (range 49 to 78 years), and mean initial PSA level was 22.5 ng/ml (range 4.2 to 95.6 ng/ml). The median Gleason sum score was 8 (range 6 to 9), and clinical stage T2c or greater was 76 patients (87.4%). Eighty-six (98.9%) completed 6 months of LHRH+EMP neo-adjuvant therapy without delay for RP. The pT0 was achieved in 4 patients (4.6%). The negative surgical margin was 73 patients (83.9%). At a mean follow-up period of 22.2 months, the PSA-free survival was 75.1%. The 2-year PSA-free survival was 83.8% with negative surgical margin, and 35.9% with positive surgical margin (P <0.0001) (Figure). CONCLUSIONS Six months of LHRH+EMP neo-adjuvant therapy followed by RP is safe and effective. Although the present study is not randomized, this treatment may improve PSA-free survival in high-risk prostate cancer. A prospective randomized trial is warranted. Hirosaki, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e258 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Koie More articles by this author Teppei Okamoto More articles by this author Kengo Imanishi More articles by this author Naoki Sugiyama More articles by this author Yuichiro Suzuki More articles by this author Kazuyuki Mori More articles by this author Shigemasa Kudoh More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Noritaka Kamimura More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2041 LOW-DOSE-RATE IODINE-125 SEEDS BRACHYTHERAPY: PSA NADIR LESS THAN 1 NG/ML AS PROGNOSTIC FACTOR

You have accessJournal of UrologyProstate Cancer: Localized X1 Apr 20102041 LOW-DOSE-RATE IODINE-125 SEEDS BRACHYTHERAPY: PSA NADIR LESS THAN 1 NG/ML AS PROGNOSTIC FACTOR Leonardo O. Reis, C.R. Monti, Lisias N. Castilho, V.D. Gialluca, José A.S. Reinato, E. Uhmann, N.S. Kawakami, and Ubirajara Ferreira Leonardo O. ReisLeonardo O. Reis More articles by this author , C.R. MontiC.R. Monti More articles by this author , Lisias N. CastilhoLisias N. Castilho More articles by this author , V.D. GiallucaV.D. Gialluca More articles by this author , José A.S. ReinatoJosé A.S. Reinato More articles by this author , E. UhmannE. Uhmann More articles by this author , N.S. KawakamiN.S. Kawakami More articles by this author , and Ubirajara FerreiraUbirajara Ferreira More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2087AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Localized prostate cancer can be treated by surgery, external beam radiation or brachytherapy (low or high dose rate). Low dose brachytherapy was introduced in 1985 and it can be used as monotherapy or associated with external radiation therapy or in local recurrence after external radiotherapy. We evaluate the outcomes and morbidity of brachytherapy with permanent seed implantation of Iodine-125 in patients with localized prostate cancer classified as low and intermediate risk in a longitudinal retrospective uncontrolled study. METHODS Between February 2000 and February 2008, 560 patients were treated with brachytherapy of whom 366 with histologically confirmed, localized tumor, clinical stage T1b, T1c, T2a and T2b, Gleason ≤7 and PSA ≤20ng/ml were evaluated. Hormonal blockade for prostate volume reduction before the brachytherapy procedure was necessary in 32.8% of patients. The dependent variable studied was the time to death (prostate cancer and other causes). The independent variables were prognostic factors properly classified according to cutoffs of literature and/or median value. Kaplan-Meier method was used to calculate overall and specific survivals. A comparison of cumulative survival curves between the different categories of the same variable was assessed using the log-rank. SPSS (version 17.0) was utilized and the level of significance was 0.05. RESULTS The mean age was 67.8 years and mean follow-up 96 months. Prostate cancer specific survival was 94% (95% CI: 92%-96%) and overall survival was 78% (95% CI: 75%-81%). The survival rates were similar for patients < or > 70 years. Specific survival rate was higher for those with Gleason score < 7 compared to 7 (93 vs 76, p = 0.012). Patients with PSA < 10 had a higher specific survival rate compared to those with PSA ≥10 (93 vs. 63, p <0.005). Patients with PSA nadir <1 ng/ml had a longer survival when compared with those with PSA nadir ≥ 1 (92 vs 64, p = 0.005). The use of neoadjuvant hormonal blockade did not influence the outcomes. Toxicity was positively related to prostate volume; 50.3% of patients had grade 1 urinary toxicity, 40.2% grade 1 rectal toxicity and 31.4% grade 2 urinary or rectal toxicity. There was no grade 3 or 4 toxicity. CONCLUSIONS Prostate low-dose-rate Iodine-125 brachytherapy is an excellent choice for conservative treatment of localized prostate cancer in selected patients presenting small prostate, < 7 Gleason score and < 10 PSA (> 92 % long term survival). PSA nadir < 1 ng/mL is a good prognostic factor in these patients. Campinas, Brazil© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e792-e793 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leonardo O. Reis More articles by this author C.R. Monti More articles by this author Lisias N. Castilho More articles by this author V.D. Gialluca More articles by this author José A.S. Reinato More articles by this author E. Uhmann More articles by this author N.S. Kawakami More articles by this author Ubirajara Ferreira More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

123 GENETIC VARIANTS SIGNIFICANTLY IMPROVE DETECTION OF PROSTATE CANCER AND ARE ASSOCIATED WITH AGGRESSIVE FEATURES IN PATIENTS WITH A “NORMAL” PSA AND DRE

You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History I1 Apr 2010123 GENETIC VARIANTS SIGNIFICANTLY IMPROVE DETECTION OF PROSTATE CANCER AND ARE ASSOCIATED WITH AGGRESSIVE FEATURES IN PATIENTS WITH A “NORMAL” PSA AND DRE Brian T. Helfand, Stacy Loeb, Matthias D. Hofer, Ronald Kim, Phillip R. Cooper, Donghui Kan, and William J. Catalona Brian T. HelfandBrian T. Helfand Chicago, IL More articles by this author , Stacy LoebStacy Loeb Baltimore, MD More articles by this author , Matthias D. HoferMatthias D. Hofer Chicago, IL More articles by this author , Ronald KimRonald Kim Chicago, IL More articles by this author , Phillip R. CooperPhillip R. Cooper Chicago, IL More articles by this author , Donghui KanDonghui Kan Chicago, IL More articles by this author , and William J. CatalonaWilliam J. Catalona Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.174AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Several reports suggest that a combination of genetic prostate cancer (CaP) susceptibility variants may independently predict CaP risk and tumor features. However, the ability to detect CaP in patients with a “normal” PSA and non-suspicious digital rectal examination (DRE) remains to be determined. Therefore, the present study examined the performance of genetic variants in prediction models for CaP risk and aggressiveness. METHODS From June 2002-May 2008, we examined 79 Caucasian men with clinical stage T1c prostate cancer diagnosed at a PSA <4.0 ng/mL and 595 controls with negative DRE and PSA <4.0 ng/mL. The genotypes for 14 CaP risk alleles (on chromosomes 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13, and Xp11) were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and non-carriers of the variants. RESULTS 12 of the variants were over-represented in CaP patients with “normal” PSA values compared to controls. Among Caucasian men with “normal” PSA values, carriers of an increasing number of genetic variants were at a significantly increased risk of CaP (p-trend<0.001). Men with ≥9 genetic variants had an OR of 6.7 (95% CI 2.0-23.7) compared to men with ≤4 variants (Table 1). On multivariate analysis with age, the genetic variants remained significant predictors of CaP risk in this population (OR 2.3, 95% CI 1.5-3.8, p=0.0005). There also was an increase in the frequency of high Gleason grade (≥7) disease in carriers of 11 variants. Specifically, a statistically significant difference was observed for the frequency of both high-grade cancer (p=0.03) and seminal vesicle invasion (p=0.02) in carriers of the 8q24 rs16901979 variant. Table 1. Cumulative Model Comparing Frequency of Genetic Variants in Patients with “Normal” PSA and DRE Carrier of Variants # Case N=(%) Control N=(%) OR (95% C.I.) p-value 0-4 9(11.4) 145(24.4) — — 5 19(24.0) 158(26.5) 1.9(0.8-4.4) 0.12 6 14(17.8) 129(21.7) 1.7(0.7-4.2) 0.21 7 19(24.0) 108(18.2) 2.8(1.2-6.5) 0.14 8 13(16.5) 43(7.2) 4.9(2.0-12.2) 0.0007 ≥9 5(6.3) 12(2.0) 6.7(1.9-23.2) 0.0026 CONCLUSIONS A substantial proportion of biopsy-detectable CaP occurs in men with PSA levels >4 ng/mL and negative DRE. In this population, genetic risk variants are significantly associated with CaP risk and may guide in the prediction of aggressive disease. Future studies are warranted to determine the utility of incorporating genetic risk alleles into CaP screening programs. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e50 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian T. Helfand Chicago, IL More articles by this author Stacy Loeb Baltimore, MD More articles by this author Matthias D. Hofer Chicago, IL More articles by this author Ronald Kim Chicago, IL More articles by this author Phillip R. Cooper Chicago, IL More articles by this author Donghui Kan Chicago, IL More articles by this author William J. Catalona Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of Robotic Training on Surgical and Pathologic Outcomes During Robot-assisted Laparoscopic Radical Prostatectomy

To prospectively compare outcomes during robotic prostatectomy between surgeons with formal training in either robotic prostatectomy (RALP) or laparoscopic prostatectomy (LRP). A total of 286 robotic prostatectomies were performed by 12 urologists between August 2008 and March 2009 as part of a new robotic surgery program at one of the largest health maintenance organizations in the United States. Four surgeons had formal training in RALP and 8 had formal training in LRP. We prospectively compared surgical and pathologic outcomes between these 2 groups of surgeons. The 4 RALP surgeons performed 121 RALPs and the 8 LRP surgeons performed 165 RALPs. Patient demographics were similar between groups. The robot-naive group had significantly more clinical stage T1c than the robot-trained group (87.9% vs 74.4%, P = .003). Prostatectomy parameters were similar between the 2 groups of surgeons in terms of prostate size, Gleason score, pathologic stage, and estimated blood loss. The robot-trained surgeons had significantly lower overall positive margin rates (24% vs 34.6%, P = .05) and lower margin rates in T3 tumors (38.5% vs 61.8%, P = .07), which were approximately statistically significant. There was no difference in margin rates in T2 tumors. The robot-trained surgeons had significantly lower apical margin rates (8.3% vs 21.2%, P = .003) and lateral margin rates (1.7% vs 7.3%, P = .05). The robot-trained surgeons had 10%-15% shorter procedure times. There was no difference in complication rates. Formal RALP training may be beneficial for surgical and pathologic outcomes of RALP compared with formal LRP training during the initial implementation of a new robotics program.

Nerve-sparing robotic prostatectomy in preoperatively high-risk patients is safe and efficacious

Objective Given the higher likelihood of extraprostatic extension in high-risk patients, many urologists will sacrifice the neurovascular bundles in such patients in an attempt to decrease the risk of positive surgical margins. In contrast, we frequently perform nerve-sparing in high-risk patients. We analyzed our outcomes in patients with preoperatively high-risk prostate cancer according to the D'Amico risk group classification, and stratified by nerve-sparing status. Materials and methods An institutional database of 1,503 robotic-assisted laparoscopic prostatectomies (RALP) was queried for patients presenting with PSA > 20 ng/ml, Gleason 8 or higher on biopsy, or clinical stage T2c or higher. Interfascial nerve-sparing was performed whenever oncologically feasible. Validated questionnaires were used to assess baseline and postoperative functional outcomes. Results Adequate follow-up was available in 123 high-risk patients. Mean serum PSA was 10.8. Bilateral, unilateral, and non-nerve-sparing was performed on 58%, 15%, and 27%, respectively. On final histopathology, 42% were organ confined; 55 patients had extraprostatic extension, and 35 had seminal vesicle invasion. Positive surgical margins occurred in 31%: 15% focal and 16% extensive. Favorable pathologic outcomes (organ-confined and negative surgical margins) were observed in 40%. Biochemical recurrence occurred in 20%. Nerve-sparing was associated with more favorable pathologic features, possibly due to selection bias. When controlling for adverse pathologic features, nerve-sparing was not associated with higher rates of positive surgical margins or biochemical recurrence. At a median follow-up of 13 months, 78% were continent and 56% were potent. The “trifecta” of continence, potency, and freedom from recurrence was achieved in 28 patients (23%). Conclusions Nerve-sparing robotic-assisted laparoscopic prostatectomy can be safely performed in patients with preoperatively high risk prostate cancer. Histopathologic and short-term oncologic outcomes at 13-month median follow-up are comparable to those in open surgical series from similar cohorts.

Long-Term Outcome of Patients with High-Risk Prostate Cancer following Radical Prostatectomy and Stage-Dependent Adjuvant Androgen Deprivation

Purpose: To present the long-term outcome of high-risk prostate cancer patients treated by radical retropubic prostatectomy (RRP) and stage-dependent adjuvant androgen deprivation therapy. Patients and Methods: Between 1989 and 2005, 2,655 patients underwent RRP by 9 surgeons. All cases (n = 372) with high-risk prostate cancer (serum PSA >20 ng/ml, and/or clinical stage T2c or greater, and/or biopsy Gleason score 8 or greater) were identified and analyzed retrospectively. Results: At 5 and 10 years, cancer-specific survival was 91.3 and 87.2%; overall survival was 84.3 and 72.1%; biochemical progression-free survival (BPFS) was 76.6 and 56.2%; clinical progression-free survival was 86.2 and 79.9%. Kaplan-Meier analysis showed significant differences with respect to pathological stage and Gleason score for cancer-specific survival, BPFS and clinical progression-free survival. In multiple analysis, the only preoperative predictor of BPFS at the 5% level was clinical stage (p = 0.0055). Conclusion: In patients with high-risk prostate cancer and a life expectancy of more than 10 years, RRP with stage-dependent adjuvant androgen deprivation therapy is a viable alternative to radiation therapy.

285 True recurrences and new primary tumours have different clinical features in invasive breast cancer patients with ipsilateral breast tumour relapse after breast-conserving treatment

We review the pathological findings of impalpable prostate cancer detected by transurethral resection (stages T1a and T1b) and needle biopsy (stage T1c). The short-term (4 years) and long-term (8 to 10 years) natural histories of untreated stage T1a prostate cancer are examined, as are options to follow patients expectantly. The findings on radical prostatectomy for stages T1a and T1b disease are reviewed and compared. Of the 64 cases of stage T1a disease 13 (20%) showed substantial tumor, including 7 with more than 1 cc of tumor, 5 with capsular penetration and 1 with a Gleason grade 4 + 5 = 9 tumor. Based on preoperative pathological parameters, one could not predict which cases had minimal versus substantial tumor. In a study from our institution that undertook complete histological examination of 39 radical prostatectomy specimens of stage T1b carcinoma, we found that all prostates contained residual carcinoma, 26% had capsular penetration and 10% had invasion of the seminal vesicles. When comparing morpho-metrically determined volumes of carcinoma with similar data from 56 patients with stage T2 carcinoma, stage T1b tumors were much more heterogeneous in grade, location and volume than were stage T2 lesions. Unless all 3 variables (grade, volume and location) were known, the final pathological stage of T1b cancers could not be predicted with confidence.Finally, we examined preoperative clinical and pathological parameters in 157 men with clinical stage T1c disease undergoing radical prostatectomy, and correlated these findings with pathological extent of disease in the surgical specimen in an attempt to identify a subset of patients with potentially biologically insignificant tumor who might be followed conservatively. Of the tumors 16% were insignificant (less than 0.2 cc, organ confined and Gleason grade less than 7), 10% were minimal (0.2 to 0.5 cc, organ confined and Gleason grade less than 7), 37% were moderate (more than 0.5 cc or capsular penetration with Gleason sum less than 7) and 37% were advanced (capsular penetration with Gleason sum 7 or more, or positive margins, positive seminal vesicles or positive lymph nodes). These findings are intermediate between those found in clinical stages T1a and T2 disease. The best model predicting insignificant tumor was a prostate specific antigen (PSA) density of less than 0.1 and no adverse pathological finding on needle biopsy or a PSA density of 0.1 to 0.15 with less than 3 mm. low to intermediate grade cancer on only 1 needle biopsy core. The positive predictive value of the model was 95% with a negative predictive value of 66%. Using this model, we accurately predicted 73% of cases with insignificant tumor. Although most impalpable prostate cancers diagnosed by needle biopsy are significant tumors that warrant definitive therapy, it may be reasonable to follow some patients whose tumors are most likely insignificant with serial PSA measurements and repeat biopsies.

Is High-Grade Prostate Cancer Easier to Find in Smaller Prostates Because There Is More High-Grade Disease to Find? – Response

We appreciate Dr. Walsh's comments about our article and acknowledge that our study provides only one possible explanation for the findings from the Prostate Cancer Prevention Trial. We are also familiar with the literature that he has cited. It is important to emphasize that the difference in the detection of high-grade cancer between finasteride and placebo during the Prostate Cancer Prevention Trial was only seen in the “for cause biopsies,” driven by prostate-specific antigen (PSA) or an abnormal prostate examination. There was no difference in the detection of high-grade cancers at the end of the study biopsy, in which no “trigger” for biopsy was used other than the rules of the protocol. If small prostates are biologically more likely to harbor high-grade disease, why would not the smaller prostates at the end of study in the finasteride arm be more likely to have high-grade disease? We appreciate his suggestion about analyzing the data from Stanford that was meticulously characterized by John McNeal. These data were recently accepted for presentation at the American Urological Association Meeting in San Francisco this year (1). We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c ( n = 723) and T2 ( n = 681) disease who underwent surgery and had detailed morphometric mapping by Dr. McNeal. Multivariate linear regression was done to assess for the effects of prostate weight (a surrogate for prostate volume) and PSA, on the volume and percentage of high-grade disease (Gleason grade 4 and 5). Among patients with T1c disease, a multivariate model including PSA and prostate weight showed that only PSA was significantly associated with the volume of high-grade disease ( P = 0.0015). Among patients with T2 disease, a similar multivariate model including PSA and prostate weight showed that only PSA was significantly associated with volume of high-grade disease ( P < 0.0001). There was a significantly greater volume of high-grade disease in the T2 patients compared with T1c patients ( P = 0.026). As we and others have shown, the performance of PSA is better for the detection of high-grade disease (2). In a radical prostatectomy series in which PSA is the driving force for biopsy (stage T1c), smaller prostates will have a higher PSA density (PSA/prostate weight) and are thus more likely to harbor high-grade disease. In patients with palpable disease (T2) in which PSA is not the only indication for biopsy, the effect of PSA exceeds the effect of prostate size in predicting high-volume and high-grade disease. These data suggest that the association between prostate size and high-grade disease seen in radical prostatectomy series may be related to ascertainment bias rather than cancer biology. The additional data we present here further supports a PSA performance bias in the observations from Prostate Cancer Prevention Trial. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.

Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging

Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging