Number Of Positive Surgical Margins Research Articles

Length and Gleason pattern at positive surgical margin after radical prostatectomy to assess risk of postoperative recurrence in localized prostate cancer.

359 Background: The prostatic apex is most popular location of positive surgical margin (PSM) at radical prostatectomy (RP) and the frequency of apex is reported to be about 20-40% of all positive cases. Prostatic apex is also reported to lack a well-defined capsule. Some recommendation suggest that reporting require location of a PSM, as well as length of PSM, though there are also reports that these classifications is inadequate in some patients. In addition, there is a lack of tumor grade at PSM in these recommendations. This study aims to investigate the impact of location, number, length, and tumor grade at PSM on biochemical recurrence (BCR) after RP. Methods: We retrospectively evaluated 1013 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. All prostatectomy specimen slides were reviewed by a single genitourinary pathologist according to ISUP 2019 criteria. PSM were subcategorized according to the length of PSM (≤ 5mm or > 5mm), Gleason pattern (GP3 vs. GP4 or 5) at PSM, the number (single or multiple), and the location (apex-only or others). Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (0.4–82 ng/ml). The median follow-up period was 69 (0.7–135) months. Pathological T stage was in 73% of pT2 (n=733), 22% of pT3a (n=229), and 4% of pT3b (n=41). PSM was found in 377 cases. Length of margin is total and 5mm in median. PSM was found at apex-only in 187 cases (50%), and others showed other single location or multiple PSM. Single PSM is found in 293 cases (78%). GP3 at PSM was found in 130 cases, GP4 in 214, and GP5 in 33. GP3 at PSM tended to be more common in apex-only PSM. GP5, extra prostatic extension (EPE), seminal vesicle invasion, IDC-P, and PSM were significant in all the patients to predict BCR. Among the patients with PSM, multivariate analysis showed that length and GP at PSM were significantly strong factors and were stronger than location and number of PSM. The prognosis in pT2 patients with PSM were significantly subcategorized into 3 groups according to the length and GP at PSM (P<0.001). Conclusions: We proposed the recurrence risk classification based on the length and the GP at PSM to predict BCR after radical prostatectomy. It is useful for prognosis prediction and high-risk group should be considered for adjuvant radiation and/or hormonal therapy in postoperative care.

Impact of positive surgical margin on biochemical recurrence in localized prostate cancer.

BackgroundWe analyzed the relationship between biochemical recurrence (BCR) and the status of positive surgical margin (PSM) in patients with pT3a prostate cancer (PCa).Materials and methodsPatients (n = 150) who underwent radical prostatectomy for pT3a PCa without nodal/distant metastasis were retrospectively reviewed between 2010 and 2013. The data regarding the status of PSM including the number, length, and margin Gleason score were collected. The predictors of BCR were analyzed using Cox regression hazard models. BCR-free survival was compared between the patients with negative surgical margin (NSM) and with PSM using Kaplan–Meier curves and log-rank tests.ResultsPSM was noted in 74 patients (49.3%). Seventy-six patients (50.7%) had NSM and 38 patients (25.3%) had single PSM. Twenty patients (13.3%) had two PSMs and 16 patients (10.7%) had ≥3 PSMs. In total patients, the multivariate analysis demonstrated that a pathological Gleason score of ≥8 was significantly associated with BCR [hazard ratio (HR), 2.173; 95% confidence interval (CI), 1.244–3.797; P = 0.038]. In patients with PSM, the number of PSM more than two was significantly associated with BCR (HR, 2.723; 95% CI, 1.256–5.902; P = 0.011). PSM length of ≥3 mm was also a significant predictive factor (HR, 1.024; 95% CI, 0.994–1.055, P = 0.042). Patients with the highest margin Gleason score of ≥4 had poorer BCR-free survival than those with that of 3/no surgical margin.ConclusionsNumber (more than one), length (≥3 mm), and higher margin Gleason score (≥4) of PSM were significantly associated with an increased likelihood of BCR in patients with pT3a PCa.

Presence and Number of Positive Surgical Margins after Radical Prostatectomy for Prostate Cancer: Effect on Oncological Outcome in a Population-Based Cohort

Introduction: Additional insight in the occurrence and number of positive surgical margins (PSM) and the potential consequences is needed, since earlier studies show divergent results. This study aims at investigating the effect of the presence and number of PSM on oncological outcomes. Methods: Retrospective population-based cohort study including 648 consecutive prostate cancer patients who underwent RP in the Southern Netherlands in 2006-2008. The effect of PSM on risk of treatment failure, defined by either biochemical recurrence or necessity of any additional therapy (Cox regression), was evaluated. Results: PSM were observed in 39%; 11% had multiple PSM. Treatment failure was observed in 26% of all patients. Multivariably, the presence (hazard ratio 2.5) and number of PSM (hazard ratios: single 2.3; multiple 3.1) were independently associated with higher treatment failure rates, unlike location of PSM. Conclusions: Treatment failure rates are high among patients with PSM, especially in those with multiple PSM. This needs to be taken into account when decisions are made on the applicability of the adjuvant and salvage therapy.

Radical prostatectomy and positive surgical margins: relationship with prostate cancer outcome.

Positive surgical margins (PSMs) are an adverse factor that may predict a worse outcome in patients submitted to radical prostatectomy (RP). However, not all of these cases will evolve to biochemical (BCR) or clinical (CR) recurrence, therefore relationship between PSMs and these recurrent events has to be correlated with other clinical and pathologic findings to indicate complementary treatment for selected patients. Of 1250 patients submitted to open retropubic radical prostatectomy (RRP), between March 1991 and June 2008, the outcome of 161 patients with PSMs and of 67 without PSMs as a control group, comprising a total of 228 cases were retrospectively reviewed. A minimum follow-up time of 2 years after surgery was considered. BCR was determined when PSA ≥ 0.2 ng/mL. CR was determined whenever there was clinical evidence of tumor. Chi-square test was used to correlate clinical and pathologic variables with PSMs. Time interval to biochemical recurrence was analyzed by the Kaplan-Meier product limit analysis using the log-rank test for comparison between groups. Univariate and multivariate Cox stepwise logistic regression models were used to identify significant predictors of risk of shorter intervals to BCR. Prostate circumference margin was the most common site with 78 cases (48.44%). Regarding the outcome of 228 cases from both groups, BCR occurred in 68 patients (29.82%), and CR in 10 (4.38%). Univariate analysis showed statistically significant associations (p < 0.001) between presence of PSMs with BCR, but not with CR (p = 0.05). At follow-up of the 161 patients with PSMs, only 61(37.8%) presented BCR, while 100 (62.8%) did not. BCR correlated with pathologic stage; Gleason score; preoperative PSA; tumor volume in the specimen; capsular and perineural invasion; presence and number of PSMs. CR correlated only with angiolymphatic invasion and Gleason score. Considering univariate analysis of clinical and pathologic factors predicting progression-free survival at 5 years, prostate weight; preoperative PSA; Gleason score; pathologic stage; tumor volume; PSMs; capsular and perineural invasion were correlated with BCR. At multivariate analysis, only Gleason score and percentage of tumor volume correlated as significant independent predictors of BCR. At univariate analysis, presence, number and location of PSMs have consistent correlation with BCR after RRP, but at follow-up BCR occurred only in 37.8% of patients with PSMs. However at multivariate analysis, the significant risk factors for BCR were percentage of tumor volume (p = 0.022) and Gleason score (p < 0.005) in the surgical specimen. Angiolymphatic invasion and Gleason score were significantly correlated with CR.

Location, extent, and multifocality of positive surgical margins for biochemical recurrence prediction after radical prostatectomy

To study the prognostic value of extent, number, and location of positive surgical margins (PSM). A total of 1,504 consecutive adjuvant treatment naive and node-negative radical prostatectomy men were included in a prospective database including extent, number, and location of PSM. Mean follow-up was 33 months. Endpoint was biochemical progression-free (bPFS) survival. The impact of margin status and characteristics was assessed in time-dependent analyses using Cox regression and Kaplan-Meier methods. PSM was reported in 26.7 % of patients. The predominant PSM locations were apex and posterior locations. Median PSM length was 4.0 mm. The 2-year bPFS was 73.7 % in PSM patients as compared to 93.0 % in NSM patients (p < 0.001). The rate and extent of PSM increased significantly with pathologic stage (p < 0.001). The extent of PSM length was linearly correlated with bPFS (p = 0.017, coefficient: -0.122). In univariable analysis, extent and number of PSM were significantly linked to outcomes. None of PSM subclassifications significantly influenced the bPFS rates in the subgroup of pT2 disease patients. Conversely, stratification by PSM location (apex vs. other locations, p = 0.008), by PSM number (p = 0.006), and by PSM length (p < 0.001) showed significant differences in pT3-4 cancer patients. In that subgroup, PSM length also added to bPFS prediction using PSM status only in multivariable models (p = 0.005). PSM subclassifications do not improve the biochemical recurrence prediction in organ-confined disease. In non-organ-confined disease, PSM length (≥3 mm), multifocality (≥3 sites), and apical location are significantly linked to poorer outcomes and could justify a more aggressive adjuvant treatment approach.

Prognostic Impact of Subclassification of Radical Prostatectomy Positive Margins by Linear Extent and Gleason Grade

We evaluated the relationship of progression to positive surgical margin linear length and Gleason grade at a positive surgical margin. We studied 2,150 prostatectomies done for pT2 or pT3a disease to determine grade, stage and surgical margin status. In patients with positive surgical margins we recorded the location, number, positive margin linear length and highest Gleason grade at a positive margin. The Kaplan-Meier method and log rank test were used to determine differences in progression-free probability among positive margin features. The concordance index was used to discriminate the accuracy of grouping surgical margin status as negative/positive vs positive margin linear length/highest Gleason grade. A total of 207 cases (10%) showed positive surgical margins, including 93 (45%) that were pT2+ and 114 (55%) that were pT3a. Patients with pT3a and positive margins had greater prostate specific antigen and tumor volume, and Gleason score 7 or greater than those with pT2+. A total of 45 patients with positive margins progressed. We then subcategorized positive margins. Of the patients 164 (79%) had 1 positive margin. Positive margin linear length was 1 mm or less, 1.1 to 3 and greater than 3 in 104 (50%), 55 (27%) and 48 cases (23%), respectively. Two-year progression-free probability was 95%, 91%, 83% and 47% in patients with negative margins and the 3 positive margin linear length groups, respectively (p <0.001). Gleason grade at a positive margin was 3 and 4/5 in 154 (74%) and 53 patients (26%), respectively. The latter group was significantly more likely to progress (p <0.001). The overall margin status concordance index was 0.636. It was not considerably enhanced by categorizing by positive surgical margin linear length/highest Gleason grade at positive margins. The linear extent of and highest Gleason grade at a positive surgical margin are associated with progression. However, subcategorization does not importantly add to predictive models using margin status only. More robust markers are needed in patients with positive surgical margins to warrant routine reporting and identify those at risk for biochemical recurrence.

First danish single-institution experience with radical prostatectomy: impact of surgical margins on biochemical outcome

This study aimed to investigate the impact of positive surgical margins (PSMs), stratified by location and extension, on biochemical outcome after radical retropubic prostatectomy (RRP). The study included data from 605 consecutive patients treated with RRP for localized prostate cancer. Patients with node-positive disease were excluded. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Univariate and multivariate analysis was used to assess risk factors. The overall PSM rate was 35.4%. Eighty-three per cent (82.7%) of these had a single PSM, whereas 17.3% of patients had two or more PSMs. Apical PSMs were present in 42.5% and non-apical in 57.5%. The presence of any PSM had a significant impact on the risk of biochemical recurrence (BR) [hazard ratio (HR) = 3.3, p < 0.0001]. Compared with margin-negative patients, both apical and non-apical PSMs increased the risk of BR (HR = 2.1 and 4.2, p = 0.02 and p < 0.0001, respectively). The number of PSMs also influenced the risk of BR (one PSM: HR = 2.8, p < 0.0001, vs two or more PSMs: HR = 5.5, p < 0.0001). In multivariate analysis, pT category, PSA and prostatectomy Gleason score independently increased the risk of BR. In an exploratory multivariate analysis of pT2 tumours, the impact of apical PSMs on biochemical recurrence-free survival (BRFS) was not statistically significant, although with an HR of 2.1. Non-apical PSM was associated with a significantly increased risk of BR (HR = 3.4, p = 0.01). Number of PSMs did not influence the risk of BR in multivariate analysis. The presence of PSMs after RRP is associated with a higher risk of BR. Multiple and non-apical PSMs are associated with a significantly higher risk of BR compared to single and apical PSMs.

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30-35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin-positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy. • To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin. • Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected. • Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin. • At a median follow-up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%. • On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82-4.32, P < 0.001) compared with the presence of Gleason grade 3. • Linear extent of margin involvement was also associated with recurrence (P= 0.009). • Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence. • On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29-4.03, P= 0.003). • The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center

Studies detailing differences in positive surgical margin among open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted laparoscopic radical prostatectomy are lacking. A retrospective review of all prostatectomies with positive surgical margin performed at our center in 2007 disclosed 99 cases, 6 (5%) of which were reinterpreted cases as having negative margins. Ninety-three cases were, therefore, included, corresponding to 37 retropubic radical prostatectomies, 19 laparoscopic radical prostatectomies, and 37 robotic-assisted laparoscopic radical prostatectomies. The relationship of positive surgical margin characteristics to clinicopathologic parameters and biochemical recurrence was assessed. The most commonly found positive surgical margin site was the apex/distal third in all groups (62% retropubic prostatectomies, 79% laparoscopic prostatectomies, 60% robotic-assisted prostatectomies). Total linear length of positive surgical margin sites was significantly correlated with preoperative prostate-specific antigen, preoperative prostate-specific antigen density, pT stage, and tumor volume (P ≤ .001). We found no significant differences among the 3 groups with respect to total linear length, number of foci, laterality, or location of positive surgical margin. The rate of biochemical recurrence was also comparable in the 3 groups. On univariate analyses, biochemical recurrence was significantly associated with preoperative prostate-specific antigen values, preoperative prostate-specific antigen density, Gleason score, number of positive surgical margins, and total linear length of positive surgical margin (P ≤ .02). Only preoperative prostate-specific antigen density and number of positive surgical margin foci were statistically significant (P ≤ .03) independent predictors of biochemical recurrence. We found no significant difference in positive surgical margin characteristics or biochemical recurrence among the 3 radical prostatectomy modalities. Preoperative prostate-specific antigen density and number of positive surgical margin foci were the only independent predictors of biochemical recurrence.

471 THE NUMBER OF POSITIVE SECTION MARGINS IN HIGH-RISK PROSTATE CANCER IS A POWERFUL AND INDEPENDENT PREDICTOR OF CANCER-SPECIFIC AND OVERALL SURVIVAL IN HIGH-RISK LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 2011471 THE NUMBER OF POSITIVE SECTION MARGINS IN HIGH-RISK PROSTATE CANCER IS A POWERFUL AND INDEPENDENT PREDICTOR OF CANCER-SPECIFIC AND OVERALL SURVIVAL IN HIGH-RISK LOCALIZED PROSTATE CANCER Steven Joniau, Paolo Gontero, Alberto Briganti, Giansilvio Marchioro, Umberto Capitanio, Pia Bader, Bertrand Tombal, Bruno Frea, Alessandro Tizzani, Hubertus Riedmiller, Hein Van Poppel, and Martin Spahn Steven JoniauSteven Joniau Leuven, Belgium More articles by this author , Paolo GonteroPaolo Gontero Turin, Italy More articles by this author , Alberto BrigantiAlberto Briganti Milan, Italy More articles by this author , Giansilvio MarchioroGiansilvio Marchioro Novara, Italy More articles by this author , Umberto CapitanioUmberto Capitanio Milan, Italy More articles by this author , Pia BaderPia Bader Karlsruhe, Germany More articles by this author , Bertrand TombalBertrand Tombal Brussels, Belgium More articles by this author , Bruno FreaBruno Frea Novara, Italy More articles by this author , Alessandro TizzaniAlessandro Tizzani Turin, Italy More articles by this author , Hubertus RiedmillerHubertus Riedmiller Würzburg, Germany More articles by this author , Hein Van PoppelHein Van Poppel Leuven, Belgium More articles by this author , and Martin SpahnMartin Spahn Würzburg, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.565AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The predictive value of positive section margins (PSM) at radical prostatectomy (RP) for disease recurrence is well established. However, controversy remains regarding the predictive value of PSM for cancer related death or overall survival. We aimed to analyze the effect of the number of PSM in a multicenter European database of RP in high-risk localized prostate cancer (PCa). METHODS We retrospectively analyzed our institutional radical prostatectomy databases and included all consecutive patients with high-risk PCa (PSA >20 OR >=cT3a OR biopsy Gleason score >=8). All patients had no evidence of nodal disease or distant metastasis on both contrast-enhanced computed tomography of the pelvis and bone scan. The last PSA value obtained prior to prostate biopsies was used in the analysis. All patients underwent a wide radical prostatectomy with pelvic LND. Histopathological data were reviewed and patients were grouped into 0, 1, 2 or >2 PSM. Clinical data and data on cancer-related death and overall survival were extracted from the case notes. Data were analyzed with Kaplan-Meier analysis and log Rank test for cancer-specific (CSS) and overall survival (OS) using number of PSM as predictor. Cox multivariate models were used to study the impact of PSM, corrected for age at surgery, pathological stage, specimen Gleason score, PSA, lymph node status, adjuvant radiotherapy (RT) and adjuvant hormonal therapy (HT). RESULTS Between 1987 and 2009, 1747 patients with high-risk PCa underwent a RP at eight European high-volume centers. In 1257 patients, number of PSM was available. Those were included for further analysis. Mean age was 65.4 years (Median 66, range 43–81). Mean PSA was 29.0 ng/ml (Median 21, range 1–630). Of the patients, 864 (68.8%) presented with >=cT3 disease. Biopsy Gleason score was >=8 in 288 (22.9%). Adjuvant treatment was administered in 51.5% (6.2% RT, 38.5% HT, 6.8% both RT and HT). Mean follow up was 74.9 months (Median 68, range 1–232). Of all patients, 57.3% had negative margins, 23.5% had 1 PSM, 7.6% had 2 PSM and 11.6% had 3 PSM. Number of PSM (0 vs. 1 vs. 2 vs. >2) was a strong predictor of CSS and OS on Kaplan-Meier analysis (both <0,0001). In the Cox multivariate models, number of PSM (coded as a continuous variable) was an independent predictor of CSS (p=0.009, HR 1.34, 95% CI 1.08–1.68) and of OS (p=0.0001, HR 1.32, 95% CI 1.16–1.52). CONCLUSIONS The number of positive surgical margins is a strong and independent predictor of CSS and OS in patients with high-risk localized PCa. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e191 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Steven Joniau Leuven, Belgium More articles by this author Paolo Gontero Turin, Italy More articles by this author Alberto Briganti Milan, Italy More articles by this author Giansilvio Marchioro Novara, Italy More articles by this author Umberto Capitanio Milan, Italy More articles by this author Pia Bader Karlsruhe, Germany More articles by this author Bertrand Tombal Brussels, Belgium More articles by this author Bruno Frea Novara, Italy More articles by this author Alessandro Tizzani Turin, Italy More articles by this author Hubertus Riedmiller Würzburg, Germany More articles by this author Hein Van Poppel Leuven, Belgium More articles by this author Martin Spahn Würzburg, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1474 PT3-PROSTATE CANCER-POSITIVE SURGICAL MARGIN AT BLADDER NECK IS AN INDEPENDANT PREDICTOR OF LOCAL FAILURE AND PROSTATE CANCER MORTALITY: RESULTS OF A PROSPECTIVE SINGLE INSTITUTION SERIES

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 20111474 PT3-PROSTATE CANCER-POSITIVE SURGICAL MARGIN AT BLADDER NECK IS AN INDEPENDANT PREDICTOR OF LOCAL FAILURE AND PROSTATE CANCER MORTALITY: RESULTS OF A PROSPECTIVE SINGLE INSTITUTION SERIES Martin Spahn, Alberto Briganti, Umberto Capitanio, Paolo Gontero, Burkhard Kneitz, Pia Bader, Hein Van Poppel, Detlef Frohneberg, and Steven Joniau Martin SpahnMartin Spahn Würzburg, Germany More articles by this author , Alberto BrigantiAlberto Briganti Milan, Italy More articles by this author , Umberto CapitanioUmberto Capitanio Milan, Italy More articles by this author , Paolo GonteroPaolo Gontero Turin, Italy More articles by this author , Burkhard KneitzBurkhard Kneitz Würzburg, Germany More articles by this author , Pia BaderPia Bader Karlsruhe, Germany More articles by this author , Hein Van PoppelHein Van Poppel Leuven, Belgium More articles by this author , Detlef FrohnebergDetlef Frohneberg Karlsruhe, Germany More articles by this author , and Steven JoniauSteven Joniau Leuven, Belgium More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1409AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have shown a positive correlation between presence of positive surgical margin (SM) and cancer recurrence and mortality. Only few addressed the importance of the location of positive SM.We hypothesized that the outcome of pts. with positive SMs (PSM) varies significantly according to their location in a large pT3 PCa series. METHODS The study included 550 consecutive pts. with high risk pPCa (PSA>20 ng/ml, cT3/cT4, bx Gleason 8–10) treated with RP+ PLND at a single institution. Of these,187 (34%) had pT3a/b disease and did not receive adjuvant radiation therapy.These pts. represented the study cohort. All pts.had detailed pathological data (presence and number of PSM (namely 1,2 or 3) that were collected prospectively. Location of PSM was recorded for all pts. and categorized as apical, posterolateral, urethral,posterior,seminal and bladder. A PSM was defined as presence of tumor cells at the inked margin of resection. Kaplan-Meier curves assessed the time to local failure and cancer specific survival (CSS) according to the number and location of PSM.The association between location of PSM was confirmed at multivariable Cox regression analyses after accounting for pathol. Gleason sum,PSA and use of adjuvant hormonal therapy. RESULTS Overall, 5,8 and 10-year CSS rates were 88, 86 and 86%, respectively, while local recurrence free rate was 82, 80 and 71% at 5–8 and 10-year follow-up, respectively. At Kaplan Meier analysis, only the presence of PSM at bladder neck was associated with both local failure and CSS (all p< 0.001). At 5 and 10 year follow-up, patients with PSM at bladder neck had significantly worse local failure (63 and 63% vs 87 and 74%; all p=0.001) and CSS rate (68 and 68% vs 94 and 91%; p<0.001) as compared to patients with negative margin at bladder neck. Conversely, no association was association between all other PSM location and CSS locations (all p=0.3). These results were confirmed at multivariable Cox regression analysis where the presence of PSM at bladder neck was the only independent predictor of both local failure (p=0.001; HR3.94) 0 and CSS (p=0.001; HR 5.61) even after accounting for all predictors. CONCLUSIONS Our study demonstrated that PSM at bladder neck is a significant predictor of local recurrence and cancer specific mortality in patients with pT3 disease even after accounting for pathological characteristics and use of adjuvant hormonal therapy. Patients with PSM at bladder neck should be thus considered for a combined, multimodal approach. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e591 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Martin Spahn Würzburg, Germany More articles by this author Alberto Briganti Milan, Italy More articles by this author Umberto Capitanio Milan, Italy More articles by this author Paolo Gontero Turin, Italy More articles by this author Burkhard Kneitz Würzburg, Germany More articles by this author Pia Bader Karlsruhe, Germany More articles by this author Hein Van Poppel Leuven, Belgium More articles by this author Detlef Frohneberg Karlsruhe, Germany More articles by this author Steven Joniau Leuven, Belgium More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prognostic relevance of number and bilaterality of positive surgical margins after radical prostatectomy

PurposePositive surgical margin (PSM) status following radical prostatectomy (RP) is a well-established prognostic factor. The aim of the present study is to evaluate whether number of PSMs or bilaterality of PSMs might have prognostic significance for biochemical recurrence (BCR) in the population with a PSM status following RP.MethodsWe evaluated 1,395 RP pathology reports from our center between 1980 and 2006. All patients who underwent (neo)-adjuvant therapy were excluded, leaving a cohort of 1,009 patients, with 249 (24.7%) subjects having a PSM at RP of whom 29.4% had multiple PSMs (≥ 2 sites), while 13.6% had bilateral PSMs. Median follow-up was 40 months (range 0–258 months). We used BCR-free survival as the primary study outcome. BCR was defined as any rise in PSA above or equal to 0.2 ng/ml.ResultsOf patients with a PSM status, 41% (95% CI: 33–49%) developed BCR within 5 years, compared to 12% (95% CI: 9–15%) in the population without a PSM. Multivariable analysis identified PSA at diagnosis and RP Gleason score as independent predictive factors for BCR. Increasing number and/or bilaterality of PSM did not lead to significant higher rates of BCR.ConclusionIn patients with a PSM, the number of positive sites or bilaterality of PSM status does not add prognostic information for risk of BCR. Survival curve slopes were different for patients with bilateral PSM, showing a significant tendency to progress to BCR earlier during follow-up than patients with unilateral PSM.

Location and number of positive surgical margins as prognostic factors of biochemical recurrence after salvage radiation therapy after radical prostatectomy

To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT). We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three-dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate-specific antigen (PSA) level of ≥ 0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥ 0.1 ng/mL above the PSA nadir after sEBRT. In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067). This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT.

Defining pathological variables to predict biochemical failure in patients with positive surgical margins at radical prostatectomy: implications for adjuvant radiotherapy

To evaluate the utility of estimated tumour volume, number of positive surgical margins (PSMs), and margin location for predicting biochemical failure in patients with PSM, in an attempt to better risk-stratify the heterogeneous group of patients at high risk of biochemical failure after radical prostatectomy (RP) for prostate cancer. We reviewed our database of 2410 patients who had RP, and isolated 423 with PSMs who had a prostate-specific antigen (PSA) nadir at undetectable levels. Kaplan-Meier curves were used for univariate survival analysis, with the log-rank test used to examine differences between survival curves. Multivariate Cox regression analysis was used to assess the independent main effect of estimated tumour volume, number of PSMs and margin location on biochemical-free survival. Increasing estimated tumour volume was directly associated with increasing risk of biochemical failure in patients with PSMs (P = 0.041). Patients with more than one PSM were at greater risk of biochemical failure than those with one PSM (P = 0.001). Margin location had no effect on biochemical-free survival in patients with PSMs. When incorporated into a multivariate Cox regression model including age, preoperative PSA level and pathological Gleason score, estimated tumour volume and number of PSMs remained independent predictors of biochemical recurrence. Coupled with other variables before and after RP, both estimated tumour volume and number of PSMs might serve to further discriminate those patients most likely to benefit from immediate adjuvant radiotherapy after RP.

The Impact of Positive Surgical Margins on Mortality Following Radical Prostatectomy During the Prostate Specific Antigen Era

The presence of a positive surgical margin at radical prostatectomy has been linked to an increased risk of postoperative biochemical recurrence. We evaluated the impact of margin status on subsequent clinical progression and mortality. We reviewed the records of 11,729 patients who underwent prostatectomy between 1990 and 2006. Survival was estimated for patients with vs without a positive margin and compared using the log rank test. Cox proportional hazards regression models were used to analyze the impact of margin status on survival. Overall 3,651 (31.1%) men were identified with a positive margin. Median postoperative followup was 8.2 years (IQR 4.4, 12.1). The 10-year biochemical recurrence-free rate for patients with and without a positive margin was 56% and 77%, respectively (p <0.001), while 10-year local recurrence-free survival was 89% vs 95% (p <0.001). Margin status also stratified systemic progression-free survival (93% vs 97%, p <0.001), cancer specific survival (96% vs 99%, p <0.001) and overall survival (83% vs 88%, p <0.001). On multivariate analysis the presence of a positive margin was associated with increased risk of biochemical recurrence (HR 1.63, 95% CI 1.47-1.80, p <0.0001), local recurrence (HR 1.78, 95% CI 1.45-2.19, p <0.0001) and receipt of salvage therapy (HR 1.79, 95% CI 1.58-2.02, p <0.0001) but was not a significant predictor of systemic progression (p = 0.95), cancer specific death (p = 0.15) or overall mortality (p = 0.16). The presence of a positive margin increased the risk of biochemical recurrence, local recurrence and the need for salvage treatment but was not independently associated with systemic progression, cancer specific death or overall mortality. These results should be considered when evaluating patients for adjuvant therapy.

Site of positive surgical margins influences biochemical recurrence after radical prostatectomy

To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates. The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate-specific antigen (PSA) level rises with the peak level >or=0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5-year risk of BCR was calculated using the Kaplan-Meier method. In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5-year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5-year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex approximately posterior. About half of the men with PSMs in the RP surgical specimen in our prospective series did not develop BCR. The risk of BCR was dependent on the site and not the number of PSMs. Adjuvant therapy should be considered in cases with anterior and basilar PSMs due to the very high risk of BCR.

Location, Extent and Number of Positive Surgical Margins Do Not Improve Accuracy of Predicting Prostate Cancer Recurrence After Radical Prostatectomy

Positive surgical margins increase the risk of biochemical recurrence after radical prostatectomy by 2 to 4-fold. The risk of biochemical recurrence may be influenced by the anatomical location and extent of positive surgical margins. In a multicenter study we analyzed the predictive usefulness of several subclassifications of positive surgical margins. The clinical information and followup data of 7,160 patients treated with radical prostatectomy alone at 1 of 3 institutions between 1995 and 2006 were modeled using Cox proportional hazards regression analysis for biochemical recurrence. Positive surgical margins were analyzed as solitary vs multiple, focal vs extensive and apical location vs other. The usefulness of these subclassifications was assessed by the improvement in predictive accuracy of nomograms containing these parameters compared to one in which the surgical margin was modeled simply as positive vs negative. The 7-year progression-free probability was 60% in patients with positive surgical margins. A positive surgical margin was significantly associated with biochemical recurrence (HR 2.3, p <0.001) after adjusting for age, prostate specific antigen, pathological Gleason score, pathological stage and year of surgery. An increased risk of biochemical recurrence was associated with multiple vs solitary positive surgical margins (adjusted HR 1.4, p = 0.002) and extensive vs focal positive surgical margins (adjusted HR 1.3, p = 0.004) on multivariable analysis. However, neither parameter improved the predictive accuracy of a nomogram compared to one in which surgical margin status was modeled as positive vs negative (concordance index 0.851 vs 0.850 vs 0.850). The number and extent of positive surgical margin significantly influence the risk of biochemical recurrence after radical prostatectomy. However, the empirical prognostic usefulness of subclassifications of positive surgical margins is limited.

Phase II Trial of Neoadjuvant Nab-Paclitaxel in High Risk Patients With Prostate Cancer Undergoing Radical Prostatectomy

Taxane based chemotherapy has activity in advanced prostate cancer but previous studies of neoadjuvant docetaxel demonstrated a prostate specific antigen response with no obvious antitumor activity. The efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel, Abraxane), a novel nanoparticle based formulation, were assessed in patients with high risk, locally advanced prostate cancer. Eligible patients had locally advanced prostatic adenocarcinoma, clinical stage cT2b or greater, Gleason score 8 or greater, or serum prostate specific antigen 15 ng/ml or greater without metastatic disease. Patients received 2 cycles of 150 mg/m(2) nab-paclitaxel weekly for 3 weeks during each 4-week cycle, followed by radical prostatectomy with bilateral lymphadenectomy. Efficacy assessments included pathological and prostate specific antigen response. A total of 19 patients completed neoadjuvant therapy and 18 underwent radical prostatectomy. Median pretreatment prostate specific antigen was 8.5 ng/ml and median Gleason score was 8. Despite the lack of complete pathological responses 5 of 18 patients (28%) had organ confined disease and 9 of 18 (50%) had specimen confined disease. Post-chemotherapy prostate specific antigen was decreased in 18 of 19 (95%) patients and median decrease was 2.9 ng/ml (35%, p <0.001). An initial prostate specific antigen after radical prostatectomy of 0.02 ng/ml or less was achieved in 17 of 18 (94%) patients. There were no significant perioperative complications. Cytoplasmic vacuolization (focal in 10 and extensive in 7) was evident in all but 1 patient (94%). Ten patients (56%) had grade 3 and 1 had grade 4 neutropenia with no febrile neutropenia. Neoadjuvant nab-paclitaxel was well tolerated. Similar to our experience with neoadjuvant docetaxel there were no pathological complete responses, although a possible histological antitumor effect was observed.

Prognostic Significance of Surgical Margin Status after Laparoscopic Radical Prostatectomy: Early Experience in a Single Institution in Japan

Objective: The objective of this study was to evaluate the impact of surgical margin status on biochemical recurrence after laparoscopic radical prostatectomy (LRP). Patients and Methods: This study included a total of 159 patients with clinically organ-confined prostate cancer who underwent LRP without any neo-adjuvant therapies between October 2000 and June 2006. The influence of the number of positive surgical margins as well as their location, which were divided into apex, posterior site, anterior site and bladder neck, on biochemical recurrence in these 159 patients was retrospectively analyzed. Results: Surgical margins were positive in 57 patients (35.8%), of whom 32 (56.1%) and 25 (43.9%) had organ-confined disease (OCD) and non-OCD, respectively. Of these 57 patients, 36 (63.2%) and 21 (36.8%) had solitary and multiple positive margins, respectively. The locations of positive surgical margins in LRP specimens from these 57 patients were as follows: 37 (64.9%) at the apex, 8 (14.0%) at the anterior site, 14 (24.6%) at the posterior site and 21 (36.8%) at the bladder neck. During the observation period of this study (median, 38 months), biochemical recurrence developed in 31/159 (19.5%) patients. On multivariate analysis, serum value of prostate specific antigen and positive surgical margin were independently associated with biochemical recurrence, irrespective of other factors examined. When the impact of the number of positive surgical margins and their location on biochemical recurrence was evaluated by multivariate analysis, the positive apex and bladder neck margins were identified as independent predictors of biochemical recurrence in overall patients, while the positive surgical margin at the apex and that at the bladder neck were independently related to biochemical recurrence in patients with OCD and non-OCD, respectively. Conclusion: These findings suggest that surgical margin status plays a crucial role in biochemical progression following LRP, and that a positive surgical margin at the apex and bladder neck could be useful predictors of biochemical recurrence in patients with OCD and non-OCD, respectively.

Positive surgical margins after radical prostatectomy: do they have an impact on biochemical or clinical progression?

To prospectively examine the effects of the margin status after radical prostatectomy (RP), the location, and the number of positive surgical margins (PSMs) on biochemical and clinical outcome, as even if there seems to be little debate that there is a higher risk of both local and distant recurrence of prostate cancer in the face of a PSM the significance of a PSM after RP is only followed for biochemical progression in most studies. From our prospective database, 406 consecutive well-described patients without neoadjuvant and 'direct postoperative' adjuvant therapy who underwent RP were included. The median age was 64.7 years, the median preoperative PSA level was 7.9 ng/mL, and the median follow-up was 5.2 years. We analysed pathological tumour stage, grading, number and location of PSMs, PSA-free survival, local recurrence-free survival, metastasis-free survival, prostate cancer-specific and, overall survival prospectively. The overall rate of PSMs was 17.2%. The number was higher in higher stage (P < 0.001) and higher grade tumours (P = 0.041). For a PSM the PSA recurrence rate was 64.3%, the local recurrence rate was 18.6%, the development of distant metastasis was 15.7% and therefore much higher than in patients with negative margins (20.5%, 2.7%, and 1.5%). A PSM was an adverse predictor for PSA-free survival (P < 0.001), local recurrence-free survival (P = 0.002), and development of metastasis (P = 0.003) on multivariate analysis. The number and location of PSMs was of no additional prognostic value. A PSM increases the risk of biochemical and clinical e.g. local, disease progression after RP. The number and location of PSMs is of minor importance. Although only approximately 20% of patients with a PSM will develop local recurrence, surgeons should continue to strive to reduce the rate of PSMs to improve cancer control.