Extracapsular Extention Research Articles

P275 - Local staging in prostate cancer: The role of capsular bulging and the length of capsular contact to predict the risk of Extracapsular Extention (ECE) at final pathology

P275 - Local staging in prostate cancer: The role of capsular bulging and the length of capsular contact to predict the risk of Extracapsular Extention (ECE) at final pathology

Predictors of biochemical recurrence of prostate cancer

Aim. To study the role of postoperative parameters in predicting the probability of development of biochemical recurrence in patients with prostate cancer with low pre-operative risk of its progression. Methods. 95 patients who underwent radical prostatectomy, were included in the study, the average age being 59.5±0.7 (44-76) years. The average levels of total and free prostate-specific antigen were 5.8±0.2 (1.71-9.9) and 1.03±0.07 (0.2-3.6) ng/ml respectively. Biochemical recurrence was defined as the level of prostate-specific antigen higher than 0.2 ng/ml after radical prostatectomy. Results. 8 (8.4%) patients during the follow-up period were diagnosed with biochemical recurrence. The average period to biochemical recurrence development was 45.8±6.7 (24-84) months. Pathomorphological examination revealed presence of tumor cells at surgical margin in 18 (18.9%) cases. Biochemical recurrence was diagnosed in 5 out of 77 (6.5%) patients with negative surgical margins and in 3 out of 18 (1.7%) patients with positive surgical margins. In our study, no correlation between the state of surgical margin and biochemical recurrence development was revealed (χ2=1.958; р=0.162). In the study group postoperative Gleason score was not prognostically significant as well (р=0.294). The average tumor volume in resected material was 11.8±1.0% (1-55%) of prostate volume (мм3). Extraprostatic extension was diagnosed in 10 (10.5%) cases. Results of univariate dispersion analysis of postoperative parameters revealed prognostic significance of tumor volume in removed specimen (р=0.007) and extracapsular extension (р=0.027). Conclusion. In our study we determined that tumor volume and extracapsular extention are independent risk factors for biochemical recurrence in prostate cancer patients with low pre-operative risk of disease progression.

Postoperative chemoradiotherapy improves survival in esophageal squamous cell cancer with extracapsular lymph node extension.

In esophageal squamous cell carcinoma (ESCC), extracapsular extention (ECE) in metastatic lymph nodes portends high rate of recurrence and poor prognosis. To our knowledge, the effectiveness of postoperative chemoradiotherapy (CRT) in these patients has never been investigated. In this retrospective study, we compared the outcomes of surgery with or without postoperative chemoradiotherapy in ESCC patients with ECE. From 2008 to 2009, 90 ECSS patients with ECE were included. Among those patients, 47 only received curative surgery alone, and 43 received additional postoperative concurrent CRT which consisted of radiotherapy (median dose 50 Gy) and chemotherapy (5-fluorouracil 1000 mg/m(2), days 1-4 and 29-32; cisplatinum 25 mg/m(2), days 1-3 and 29-31). Patients treated with postoperative CRT had significantly more T3/4 tumors (p=0.023). Based on log-rank stratified by T stage, postoperative adjuvant CRT significantly improved the overall survival (p=0.017) and progression free survival (p=0.002). In multivariate analysis, adjuvant CRT was identified as an independent prognostic factor (HR=0.494, CI 0.290-0.844, p=0.010). Compared with surgery alone, the CRT group had significantly fewer cases of regional recurrence (P=0.048) and overall recurrence (P=0.024). However, there was no significant difference in distant metastasis between two groups (P=0.755). In conclusion, our data suggest that the postoperative adjuvant CRT might be beneficial in selected subgroups of ESCC patients with ECE. To further verify these results, a prospective trial with a large sample size is needed.

External Beam Radiation Therapy Is Associated With Increased Variability in Retinal Venous Oxygenation

Purpose/Objective(s): The prognosis for squamous cell head and neck cancer after surgical treatment and adjuvant chemo radiation is unsatisfactory in cases of close resection margins <5 mm (CM) or extracapsular extent at the lymph nodes (ECE). Therefore, we conducted a multicenter Phase II study to investigate the toxicity and efficacy of adjuvant radiation therapy in combination with concurrent cisplatin, 5-fluorouracil (5-FU), and cetuximab followed by maintenance therapy with cetuximab for 6 months. Here, we present the preliminary results on feasibility and toxicity. Materials/Methods: Patients with squamous cell cancer of the head and neck after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin (20 mg/m d1-5 and d29-33) and 5-FU as continuous infusion (600 mg/m d1-d5 + d29-33) were given concurrently to postoperative radiation therapy using an integrated boost IMRT-technique (1.8/ 2.0/2.2 Gy QD) to a total dose of 61.6 Gy. Cetuximab started 7 days prior chemoradiation therapy with a loading dose of 400 mg/m followed by weekly cetuximab (250 mg/m) during chemoradiation therapy. Maintenance cetuximab started after completion of chemoradiation therapy plus cetuximab with 500 mg/m every 2 weeks over a 6-month period. Results: Fifty-five of 80 planned pts (46 male, 9 female, mean age 55.6, range, 29-70 years) have finished chemoradiation therapy, 50 are evaluable for toxicity. Concurrent Chemoradiation therapy plus Cetuximab was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts Cetuximab was discontinued during the last 2 weeks or at the end of chemo radiation therapy. Of those pts embarking on maintenance therapy, 80% were still on Cetuximab after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant radio chemotherapy in combination with cetuximab followed by maintenance cetuximab is feasible with toxicity in the expected range. Compliance to maintenance cetuximab was satisfactory during the first 3-5 months. Author Disclosure: C. Matuschek: None. E. Boelke: None. C. Belka: None. U. Ganswindt: None. M. Henke: None. P. Stegmaier: None. M. Bamberg: None. S. Welz: None. J. Debus: None. W. Budach: None.

Feasibility of 6-month maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck

Close resection margins < 5mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phaseII study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article. Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6Gy (1.8/2.0/2.2Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20mg/m(2), days1-5 and days29-33) and 5-fluorouracil (5-FU) as continuous infusion (600mg/m(2), days1-5 + days29-33) were given concurrently. Cetuximab was started 7days prior to radiochemotherapy at 400mg/m(2) followed by weekly doses of 250mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500mg/m(2) every 2weeks for 6months. Of the 55patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning gradeIII/IV toxicities of skin and mucosa. Grade3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3months and 63 % at 5months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients. Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5months is moderate.

Inherently Multimodal Nanoparticle-Driven Tracking and Real-Time Delineation of Orthotopic Prostate Tumors and Micrometastases

Prostate cancer is the most common cancer among men and the second cause of male cancer-related deaths. There are currently three critical needs in prostate cancer imaging to personalize cancer treatment: (1) accurate intraprostatic imaging for multiple foci and extra-capsular extent; (2) monitoring local and systemic treatment response and predicting recurrence; and (3) more sensitive imaging of occult prostate cancer bone metastases. Recently, our lab developed porphysomes, inherently multimodal, all-organic nanoparticles with flexible and robust radiochemistry. Herein, we validate the first in vivo application of 64Cu-porphysomes in clinically relevant orthotopic prostate and bony metastatic cancer models. We demonstrate clear multimodal delineation of orthotopic tumors on both the macro- and the microscopic scales (using both PET and fluorescence) and sensitively detected small bony metastases (<2 mm). The unique and multifaceted properties of porphysomes offers a promising all-in-one prostate cancer imaging agent for tumor detection and treatment response/recurrence monitoring using both radionuclide- and photonic-based strategies.

Validation of Three Breast Cancer Nomograms and a New Formula for Predicting Non-sentinel Lymph Node Status

The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.

Feasibility of 6 months of maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck (HNC).

e16033 Background: The prognosis for HNC patients (pts) after surgical treatment and adjuvant chemoradiation (CRT) is unsatisfactory in case of close resection margin &lt;5 mm (CM) or extra capsular extent at the lymph nodes (ECE). Therefore we conducted a multicenter phase II study to investigate the toxicity and efficacy of adjuvant radiotherapy (RT) in combination with concurrent cisplatin, 5- fluorouracil (5FU), and cetuximab (CTX) followed by maintenance therapy with CTX for 6 months. Here, we present the preliminary results on feasibility and toxicity. Methods: HNC pts after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin [20 mg/m2 d1-5 and d29-33] and 5-FU (CI 600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative RT using an integrated boost IMRT-technique (1.8/2.0/2.2Gy QD) to a total dose of 61.6 Gy. CTX started 7 days prior CRT with a loading dose of 400 mg/m2 followed by weekly CTX (250 mg/m2) during CRT. Maintenance CTX started after completion of CRT plus CTX with 500 mg/m² every 2 weeks over a 6-month period. Results: 55 of 80 planned pts (46 male, 9 female, mean age 55.6, range 29-70 years) have finished CRT, 50 are evaluable for toxicity. Concurrent CRT plus CTX was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reaction outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). CTX was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts CTX was discontinued during the last 2 weeks or at the end of CRT. Of those pts embarking on maintenance therapy, 80% were still on CTX after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant CRT in combination with CTX followed by maintenance CTX is feasible with toxicity in the expected range. Compliance to maintenance CTX was satisfactory during the first 3-5 months.

57P Validation of Three Breast Cancer Nomograms for Predicting the Non-Sentinel Lymph Node Metastases and a New Formula for Predicting Non-Sentinel Lymph Node Status. (Second Study from Turkey-First Unicenter Study)

ABSTRACT Introduction Patients who have positive SLNB should undergo to axillary lymph node dissection (ALND), about 40-70% of them have no nonsentinel lymph node (NSLN) metastasis. Purpose The aim of the study is to evaluate the available breast nomograms (MSKCC,Stanford,Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine the variables on NSLNM in the SLN positive breast Cancer (BC) patients in the our population. Method We retrospectively reviewed BC patients who underwent SLN biopsy. One hundred and seventy SLN biopsy positive patients who had completion axillary lymph node dissection were evaluated. We described two groups; group one NSLN negative (70 patients), group two NSLN positive (100 patients). Four factors were found to contribute significantly to the logistic regression model. After multiple logistic regression analysis of significant parameters, we designed a new formula to predict non-sentinel lymph node metastasis, based on the multivariate analysis. The areas under (AUC) the receiver operating characteristic curve (ROC) were used to describe the performance of the diagnostic value of nomograms and our new nomogram. Results After stepwise multiple logistic regression analysis four parameters found statistically significant. AUC results for each nomograms: MSKCC: 0,713 / Tenon: 0,671 / Stanford: 0,534 / DEU: 0,814. Conclusion The MSKCC nomogram was good discriminator of NSLN metastasis in SLN positive BC patients for our population. A newly created formula depending on four factors (Multifocality, LVI, proportion of positive SLN among total SLN, SLN extracapsular extention) is the best prediction toll for discriminate of NSLN metastasis in SLN positive BC patients for our population. Disclosure All authors have declared no conflicts of interest.

Analyse des résultats anatomopathologiques des pièces de prostatectomie radicale des patients répondant aux critères de surveillance active du cancer de prostate

To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance. The data of patients who underwent a radical prostatectomy by a single surgeon between 2002 and 2007 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA< or =10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 50% of malignant tissue in each positive biopsy core and a PSA density inferior or equal to 0.15 ng/ml/cc. Two hundred and seventy-three patients were operated, including 25 (9.2%) who met all the criteria for active surveillance. Mean age was 61 years (55-68). The mean preoperative PSA was 6.6 ng/mL (2.5-10). Clinical stage of the tumor was T1c in 84% of patients and T2a in 16%. Biopsy Gleason score was 3+3 in 92%, 2+3 in 4% and 2+2 in 4%. Pathological study of the surgical specimen showed that 28% of the tumors were pT2a, 8% pT2b, 40% pT2c and 20% pT3a. One tumor was pT0. The pathological Gleason score was 3+3 in 68% of patients and 3+4 in 28%. Surgical specimen showed a higher Gleason score in 44% of cases, but there were no cases of predominant grade 4. After a mean follow-up of 19.2 months, there was no clinical or biological recurrence. In our experience, 20% of patients who meet the criteria for active surveillance show an extracapsular extent of the tumor on pathological analysis. Active surveillance is still under evaluation. Its main risk is to underestimate the aggressiveness of the tumor at the time of diagnosis.

Bilateral Cavernous Nerve Interposition Grafting During Radical Retropubic Prostatectomy: Memorial Sloan-Kettering Cancer Center Experience

Cavernous nerve graft is an option for men requiring bilateral cavernous nerve resection for cancer control during radical prostatectomy. We determined the success rate and identified determinants of success of bilateral cavernous nerve grafting following resection of the 2 nerves during radical prostatectomy in patients who were potent preoperatively. We retrospectively reviewed the records of 44 consecutive patients who underwent bilateral nerve grafting from 1999 to 2004. Postoperative erectile function was defined as the achievement of erections satisfactory for intercourse with or without oral medication. We calculated cumulative erectile function recovery rates using Kaplan-Meier curves. The log rank test was used to compare variables affecting erectile function recovery with p <0.0083 considered significant after adjusting for the number of variables evaluated using the Bonferroni correction. The overall 5-year cumulative recovery of erectile function permitting penetration was 34% and the rate of consistent penetration was 11%. None of the analyzed variables were significantly associated with recovery of postoperative erectile function, including patient age (p = 0.3), incomplete bilateral cavernous nerve resection (p = 0.045), sural nerve grafts compared to genitofemoral or ilioinguinal nerves as donor sites (p = 0.067), post-radiation salvage radical prostatectomy (p = 0.15), neoadjuvant hormone therapy (p = 0.7) and comorbidities (p = 0.15) or medications (p = 0.4) affecting EF. Bilateral cavernous nerve grafts might be beneficial in select patients. A definitive answer awaits the performance of a multi-institutional, randomized, controlled trial.

Predicting time to metastatic progression from biochemical recurrence after radical prostatectomy

4642 Background: Many patients with a rising PSA (biochemical recurrence; BCR), after radical prostatectomy (RP) will eventually develop metastases, but our ability to predict the risk of progression over time is limited. We developed a model (nomogram) that incorporates all known prognostic factors to predict the probability of Mets 8 years after BCR. Methods: We queried our multidisciplinary prostate cancer database for patients who developed BCR after RP for clinically localized disease. We defined BCR as 3 subsequent peaks in PSA ≥0.1 ng/ml. After excluding 14 adjuvant radiation patients, we found 816 followed for 0.1 to 15.9 (median 4.3) years after BCR. We recorded times of secondary treatment (radiation or hormonal therapy), metastases and death. A Cox proportional hazards analysis incorporated preoperative PSA, use of neoadjuvant hormonal therapy (NHT), time from surgery to BCR, pathologic findings [surgical margin, presence of extracapsular extention, seminal vesicle invasion (SVI), lymph node metastases, and pathologic Gleason score (GS)], PSA doubling time (PSA DT) and PSA value at BCR into a predictive model. Results: Secondary treatment for BCR only was a frequent event: 216 patients (26.5%) had radiation therapy and 340 (41.7%) hormones; 157 developed metastases, 67 died of other causes and 244 (29.9%) were alive with out metastases or secondary treatment at last follow-up. In the multivariate model the following predicted metastatic progression: high preoperative PSA (P=0.01), use of NHT (P=0.02), presence of SVI (P=0.005), high pathologic GS (P<0.001), short PSA DT (P=0.01) and high PSA value at BCR (P<0.001). A nomogram for predicting risk of metastases at 8 years was constructed with a concordance index of 0.75. Conclusions: Multiple disease factors affect the risk of metastases after BCR. This new nomogram helps predict, at the time of BCR after RP, the 8-year probability of metastases for the individual patient and provides a useful tool to identify patients appropriate for intervention trials or surveillance. No significant financial relationships to disclose.

Predicting time to metastatic progression from biochemical recurrence after radical prostatectomy

4642 Background: Many patients with a rising PSA (biochemical recurrence; BCR), after radical prostatectomy (RP) will eventually develop metastases, but our ability to predict the risk of progression over time is limited. We developed a model (nomogram) that incorporates all known prognostic factors to predict the probability of Mets 8 years after BCR. Methods: We queried our multidisciplinary prostate cancer database for patients who developed BCR after RP for clinically localized disease. We defined BCR as 3 subsequent peaks in PSA ≥0.1 ng/ml. After excluding 14 adjuvant radiation patients, we found 816 followed for 0.1 to 15.9 (median 4.3) years after BCR. We recorded times of secondary treatment (radiation or hormonal therapy), metastases and death. A Cox proportional hazards analysis incorporated preoperative PSA, use of neoadjuvant hormonal therapy (NHT), time from surgery to BCR, pathologic findings [surgical margin, presence of extracapsular extention, seminal vesicle invasion (SVI), lymph node metastases, and pathologic Gleason score (GS)], PSA doubling time (PSA DT) and PSA value at BCR into a predictive model. Results: Secondary treatment for BCR only was a frequent event: 216 patients (26.5%) had radiation therapy and 340 (41.7%) hormones; 157 developed metastases, 67 died of other causes and 244 (29.9%) were alive with out metastases or secondary treatment at last follow-up. In the multivariate model the following predicted metastatic progression: high preoperative PSA (P=0.01), use of NHT (P=0.02), presence of SVI (P=0.005), high pathologic GS (P<0.001), short PSA DT (P=0.01) and high PSA value at BCR (P<0.001). A nomogram for predicting risk of metastases at 8 years was constructed with a concordance index of 0.75. Conclusions: Multiple disease factors affect the risk of metastases after BCR. This new nomogram helps predict, at the time of BCR after RP, the 8-year probability of metastases for the individual patient and provides a useful tool to identify patients appropriate for intervention trials or surveillance. No significant financial relationships to disclose.

453 Loss of heterozygosity at 7Q31 is a frequent and early event in prostate cancer

Recent studies have identified regions on chromosome arms 8p, 10q, 16q and 18q that are frequently deleted in human prostate cancer. We have previously described a loss of heterozygosity (LOH) at the MET locus on chromosome band 7q31, in a study of 20 localized prostate tumors. To determine whether a region on the 7q arm is important in the initiation and/or progression of prostate cancer, prostate tissue from 13 patients with confined prostate tumors, 17 with local extracapsular extention and 13 with metastatic forms were analysed for LOH, using a DNA probe for restriction fragment length polymorphism (RFLP, pMetH) and eight CA microsatellite repeats (seven on 7q21–q33, one on 7p). Twenty of the 43 cases studied (47%) showed LOH at one or more 7q loci. The most frequently deleted region was chromosome 7q31.1–7q31.2, while the centromeric locus on 7q21 was generally conserved. The percentage of LOH was normally distributed around the D7S480 locus. Moreover, the rate of LOH in the 7q31 region was lower in metastatic tumors than in localized tumors. These results strongly suggest the presence of a tumor suppressor gene on the chromosome band 7q31 with an important role in the early stages of prostate cancer.