Post-chemotherapy Lymph Node Research Articles

Determination of risk factors for progression in patients with viable tumor at post-chemotherapy lymph node dissection due to disseminated non-seminomatous germ-cell tumors.

To assess the clinical variables that effect progression in patients with viable tumor after post-chemotherapy lymph node dissection due to disseminated non-seminomatous germ-cell tumors. We performed a retrospective analysis of 32 patients with viable tumor after PC-RPLND, operated between 1990 and 2016. Patients were categorized into 2 groups as favorable and non-favorable (intermedia and poor) according to International Germ Cell Consensus Classification (IGCCC). Tumor size was determined as the largest dimension of retroperitoneal mass. Clinical factors and adjuvant chemotherapy were evaluated to impact on recurrence free survival (RFS) and overall survival (OS). The median age of the patients and follow-up duration were 28.5 (17-51) years and 51.5 (4-253) months, respectively. 5-year RFS and OS were 57.8-66.8%, respectively. On univariate analysis, percentage of viable tumor, IGCCC risk group, primary site, second-line chemotherapy and surgical margin status were significant for RFS (p = 0.034, p = 0.002, p < 0.001, p = 0.011 and p < 0.001, respectively), while IGCCC risk group, second-line chemotherapy and surgical margin status were significant for OS (p = 0.004, p = 0.010 and p < 0.001, respectively). On multivariate analysis, second-line chemotherapy and surgical margin were independent risk factors for RFS (p = 0.016, HR 4.927 95% CI 1.34-18.02 and p < 0.001, OR 9.147 95% CI 2.61-31.98, respectively) and surgical margin status was the only predictor of OS (p = 0.038, HR 3.874 95% CI 1.07-13.69). Retroperitoneal lymph node dissection with negative surgical margin is essential for patients with viable residual tumor after chemotherapy. Need for second-line chemotherapy shows risk of progression.

Radiomics allows for detection of benign and malignant histopathology in patients with metastatic testicular germ cell tumors prior to post-chemotherapy retroperitoneal lymph node dissection.

To evaluate whether a computed tomography (CT) radiomics-based machine learning classifier can predict histopathology of lymph nodes (LNs) after post-chemotherapy LN dissection (pcRPLND) in patients with metastatic non-seminomatous testicular germ cell tumors (NSTGCTs). Eighty patients with retroperitoneal LN metastases and contrast-enhanced CT were included into this retrospective study. Resected LNs were histopathologically classified into "benign" (necrosis/fibrosis) or "malignant" (viable tumor/teratoma). On CT imaging, 204 corresponding LNs were segmented and 97 radiomic features per LN were extracted after standardized image processing. The dataset was split into training, test, and validation sets. After stepwise feature reduction based on reproducibility, variable importance, and correlation analyses, a gradient-boosted tree was trained and tuned on the selected most important features using the training and test datasets. Model validation was performed on the independent validation dataset. The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a misclassification of 8 of 36 benign LNs as malignant and 4 of 25 malignant LNs as benign (sensitivity 88%, specificity 72%, negative predictive value 88%). In contrast, a model containing only the LN volume resulted in a classification accuracy of 0.68 with 64% sensitivity and 68% specificity. CT radiomics represents an exciting new tool for improved prediction of the presence of malignant histopathology in retroperitoneal LN metastases from NSTGCTs, aiming at reducing overtreatment in this group of young patients. Thus, the presented approach should be combined with established clinical biomarkers and further validated in larger, prospective clinical trials. • Patients with metastatic non-seminomatous testicular germ cell tumors undergoing post-chemotherapy retroperitoneal lymph node dissection of residual lesions show overtreatment in up to 50%. • We assessed whether a CT radiomics-based machine learning classifier can predict histopathology of lymph nodes after post-chemotherapy lymph node dissection. • The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a sensitivity of 88% and a specificity of 78%, thus allowing for prediction of the presence of viable tumor or teratoma in retroperitoneal lymph node metastases.

Postchemotherapy lymph node dissection for isolated retroperitoneal nodal recurrences for penile cancer: Is cure possible in highly selected cases?

Outcomes for advanced penile carcinoma remain poor with limited options for curative treatment. Nodal recurrences represent worse prognosis and are typically treated with a combination of radiation, chemotherapy, or consolidative resection. Although the ideal management for recurrences remains unknown, there is some evidence supporting the role of chemotherapy followed by consolidative resection. Using a multimodal strategy, we describe the curative potential of postchemotherapy retroperitoneal lymph node dissection for penile cancer patients with isolated locoregional recurrences in the retroperitoneum.

Laparoscopic and robotic postchemotherapy retroperitoneal lymph node dissection

Open surgical postchemotherapy retroperitoneal lymph node dissection remains the standard of care. On the contrary, laparoscopy is an emerging technique and reports of laparoscopic lymph node dissection postchemotherapy are increasing. Our purpose is to present indications, technique and outcomes of laparoscopic postchemo retroperitoneal lymph node dissection. With growing expertise and knowledge the morbidity of the laparoscopic approach is much reduced compared with open surgery with the same oncological outcome. Robotic surgery is a more recent approach with growing usage in urology. However, no reports of robotic postchemotherapy lymph node dissection are available. In expert hands laparoscopic lymph node dissection is a feasible technique, offering less morbidity to patients with good oncological results.

Postchemotherapy retroperitoneal lymph node dissection for advanced germ cell tumors at a Japanese single high-volume center.

331 Background: Post chemotherapy lymph node dissection (PCRPLND) plays important role in the management of advanced germ cell tumors (GCTs). Guidelines recommend performing PCRPLND for advanced GCT with tumor marker normalization. The aim of this study is to assess efficacy and preserve antegrade ejaculation at Japanese single high volume center. Methods: One hundred and eleven patients who had PCRPLND at Kyoto Prefectural University of Medicine between June 1998 and August 2011 were studied. Five cases of desperation RPLND and 6 cases of laparoscopic RPLND were also included. Results: Median age was 30 years old (17-68y.o.). Seminoma was 11 cases and nonseminoma was 100 cases at primary site. Good, intermediate and poor prognosis group of International Germ Cell Cancer classification was 48, 35 and 20 cases, respectively. Seventy-four cases were treated after induction chemotherapy and 41 cases were done after salvage chemotherapy. median operation time was 590 min. and median blood loss was 1650ml. Nerve-sparing procedure were performed for 90 cases. Antegrade ejaculation was preserved in 83.5% of this cohort. Especially, antegrade ejaculation was preserved in 93.3% of the patients with bilateral nerve sparing. Necrosi/fibrosis, teratoma only and viable cancer were detected in 54.4%, 32.5% and 13.1%, respectively. Additional procedure such as nephrectomy was performed in 12 cases. Five-year overall survival was 95.1%. In the desperation group, only one case is alive without disease. Conclusions: The results of PCRPLND at high volume center could be satisfied and preservation of antegrade ejaculation could be obtained. On the other hand, indication of desperation RPLND had to be carefully considered.

P1-06-17: A New Pathological Response Index (PRI) for Neoadjuvant Chemotherapy Accurately Predicts Clinical Outcomes of Locally Advanced Breast Cancers (LAPBC).

Abstract Pathological complete response (pCR) after neoadjuvant chemotherapy predicts overall survival that is independent of treatment regimen. However; pCR is not a perfect surrogate for overall survival, given that a significant number of patients who did not achieve pCR also have a good prognosis and a small number of patients with pCR still develop recurrences. Furthermore, residual cancer cells after neoadjuvant therapy includes a wide range of responses from near pCR to complete resistance. In this study we performed a comprehensive pathological assessment for 245 surgical specimens of LAPBC, treated at a single institution, removed after receiving neoadjuvant anthracycline combination chemotherapy only (n=152) or with Taxane (n=93) with median follow up 42 months. Progression free survival (PFS) was used as the study endpoint. For comparison, residual cancer burden (RCB) was calculated using web calculator at www.mdanderson,org/breast_BCR. A multivariate Cox regression model revealed that size of the residual invasive carcinoma (OR; 3.2, CI 95%; 1.6−6.1, p=0.001), presence of lympho-vascular invasion (OR; 2.4, CI 95%; 1.3−4.3, p=0.004), absence of any pathological evidence of response at the site of the primary tumour or axillary lymph nodes after CT (OR; 3.2, CI 95%; 2.2−8.0, p=0.00001), and presence of at least one apical lymph node metastases (OR; 4.2, CI 95%; 1.5−6.8, p=0.003) at surgery were significantly associated with shorter PFS. These results were used to develop a pathological response index (PRI) from which 5 prognostic subgroups with distinct clinical outcomes were identified. Patients with PRI-PG1 (n=110; 49%) had a good clinical outcomes in both ER+ (3-year PFS; 91%) and ER- tumours (3-year PFS; 84%). Moreover, patients with PRI-PGI who did not show pCR (n=69) had equivalent overall and PFS as those with PRI-PG1 who achieved pCR (n=41); p=NS. Patients with PRI-PG2-5, had a 5 fold increase in the risk of progression compared to those with PRI-PG1 (HR; 5.2, CI 95%; 2.9−9.6, p≤0.0001). ER+ patients with PRI-PG3-5 (25% of ER+ cases) had shorter 3-year PFS 30%) compared to those ER+ with PRI PG1-2 (91%) despite treatment with adjuvant hormonal therapy (HR=6.5, CI 95%; 2.8−14.7, p&amp;lt;0.0001). Similarly, HER2 positive patients with PRI- PG3-5 (20% of HER2+ patients) showed very rapid progression within &amp;lt; 3 years (PFS; 10%) vs. those with PRI-PG1-2 (PFS; 82%) despite trastuzumab treatment (HR=8.4; CI 95%; 2.8−25.0, p&amp;lt;0.0001). In conclusion, a pathological response index including size of residual tumour, post chemotherapy lymph node pathological stage, lympho-vascular invasion and any evidence of fibrotic/response reaction following neoadjuvant chemotherapy may accurately predict the chance of disease progression, identify a greater proportion of patients (&amp;gt;twice as many as pCR) who could potentially benefit from the neoadjuvant chemotherapy and may be able to spared further adjuvant therapy. Furthermore this new PRI may help to improve the sensitivity of pathological response as a study end-point for predicting tumours response to a given neoadjuvant regimen and enable biological markers to be studied in a good prognostic group in additional to pCR. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-17.

Management of testicular neoplasms in France and compliance with national guidelines.

4580 Background: Testicular neoplasms (TN) are uncommon and curable tumors with standardized treatment. Guidelines are available. Treatments may lead to adverse effects (long-term severe toxicities, secondary cancer), occurring among young men. Our aim was to describe the primary TN management in France and to evaluate compliance with the national guidelines. Methods: Cases of TN diagnosed in 2003-2004 were identified from 11 general official exhaustive cancer registries. A detailed medical chart was used to collect individual data on tumor description and management. National guidelines published in 2002 were used as reference (Progrès en Urologie 2002;12:71-78). A conformity list was defined by a group of experts. Each criterion could be in accordance with the recommendations, severely noncompliant (disagreement with the recommendations with a potential impact on outcome), marginally noncompliant (no effect on patient outcome) and noncompliant but justifiable (noncompliance explained by patient or tumor characteristics). Results: 256 patients with testicular seminoma (TS) and 197 with testicular nonseminoma (TNS) were included: 69% had a stage I, 16% a stage II, 16% a stage III and 11% an undetermined one. Globally only 10% of patients with TS and 12% with TNS received a totally conform management (all stages combined). When restricting to therapeutic steps only, conformity to standard guideline was 44% and 28% respectively for TS and TNS. Most severe noncompliance are summarized in the Table. Conclusions: Based on exhaustive French cancer registries, the real-life TN management is quite disappointing, specially for pretherapeutic step, surveillance for TNS, chemotherapy for TNS and TS and post chemotherapy surgery. This study highlights the need for larger guidelines diffusion on every contributor (pathologist, urologist, medical oncologist and radio-oncologist). It might also be considered as a plea for patients’ centralization in reference centers. TS TNS Tumor markers at diagnosis 40% 33% Histology report 35% 46% Radiotherapy 31% / Chemotherapy 62% 58% Active surveillance only / 95% Postchemotherapy lymph node dissection / 70% No significant financial relationships to disclose.

562 OUTCOMES IN PATIENTS WITH VIABLE CANCER AT POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disease I1 Apr 2010562 OUTCOMES IN PATIENTS WITH VIABLE CANCER AT POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION Shilajit Kundu, Brett Carver, Nicholas Karanikolas, George Bosl, Robert Motzer, Dean Bajorin, Darren Feldman, and Joel Sheinfeld Shilajit KunduShilajit Kundu More articles by this author , Brett CarverBrett Carver More articles by this author , Nicholas KaranikolasNicholas Karanikolas More articles by this author , George BoslGeorge Bosl More articles by this author , Robert MotzerRobert Motzer More articles by this author , Dean BajorinDean Bajorin More articles by this author , Darren FeldmanDarren Feldman More articles by this author , and Joel SheinfeldJoel Sheinfeld More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.808AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Risk stratification for patients with advanced disease, completeness of surgery, and improved chemotherapy regimens have resulted in a decrease in the incidence of viable germ cell tumor in resected retroperitoneal specimens. We report on the incidence and clinical outcomes of patients treated with post-chemotherapy lymph node dissection that had residual viable GCT in the retroperitoneum. METHODS From 1989 to 2009, 985 patients with advanced NSGCT were treated with induction and/or salvage chemotherapy followed by PC-RPLND. Following institutional review board approval, complete clinical and pathologic data were obtained from our prospective surgical database. Ninety patients were found to have viable GCT at RPLND. Clinical and pathologic features of patients with viable cancer are reported. Categorical variables were compared using the chi-square or Fisher's exact test. Logistic regression was used to assess factors that were associated with the presence of viable cancer. Survival analysis was performed using the Kaplan-Meier method, and comparisons were made using the log-rank test. RESULTS Viable cancer was more prevalent in patients with increasing clinical stage, IGCCCG risk category, pre-chemotherapy mass size, pre-surgery mass size, elevated AFP, elevated HCG, and patients that received 2nd/3rd line vs. induction chemotherapy. Actuarial 5-year relapse free survival (RFS) was 62% (95% CI 49, 72). RFS was not significantly different between patients that received induction chemotherapy vs. 2nd/3rd line chemotherapy. Adjuvant chemotherapy significantly improved RFS rates in patients that received induction chemotherapy, but not in patients that received 2nd/3rd line chemotherapy prior to PC-RPLND. Actuarial 5-year disease specific survival (DSS) was 71% (95%CI 58,80). Disease specific survival was significantly worse in patients that received 2nd/3rd line chemotherapy (p=0.05). CONCLUSIONS Following chemotherapy a significant number of patients with viable cancer are cured after surgery even in the setting of salvage chemotherapy. Surgery remains an integral component in the multidisciplinary treatment of patients with advanced GCTs. Cure can be achieved in 78% of patients after induction chemo and 58% of patients after salvage chemotherapy at 5 years. New York, NY© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e220-e221 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shilajit Kundu More articles by this author Brett Carver More articles by this author Nicholas Karanikolas More articles by this author George Bosl More articles by this author Robert Motzer More articles by this author Dean Bajorin More articles by this author Darren Feldman More articles by this author Joel Sheinfeld More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The indication for postchemotherapy lymph node dissection in clinical stage IS nonseminomatous germ cell tumor

The initial management of patients with clinical stage IS (cIS) nonseminomatous germ cell tumor (NSGCT) has evolved from primary retroperitoneal lymph node dissection (RPLND) to induction chemotherapy. The objectives of the current study were to determine the clinical outcome, patterns of relapse, and incidence of teratoma in the retroperitoneum for men with cIS NSGCT. Between 1988 and 2004, 24 patients with cIS stage NSGCT were evaluated and treated at Memorial Sloan-Kettering Cancer Center. Clinical and pathologic data were obtained from the institutional prospective database. Seven patients underwent primary RPLND, and 17 patients received induction chemotherapy as initial management. Clinical outcomes, patterns of relapse, and pathologic findings were reported. Six of the 7 patients who underwent primary RPLND had viable germ cell tumor (GCT) present. Four of those patients did not receive adjuvant chemotherapy, and all experienced systemic relapse. Of the 17 patients who received induction chemotherapy, 3 patients underwent elective postchemotherapy RPLND (PC-RPLND), and 14 patients were followed expectantly. Four patients who were followed expectantly relapsed in the retroperitoneum and underwent PC-RPLND. Of the 7 patients who underwent PC-RPLND, 1 patient had fibrosis (14%), but 6 patients (86%) had teratoma, including 1 patient who also had a viable GCT in the retroperitoneum. Overall, the incidence of teratoma or viable GCT in the retroperitoneum after chemotherapy was 43% (6 of 14 patients). At a median follow-up of 35 months, 23 men remained alive, and 1 man had died of disease. The current data suggest that patients with cIS stage NSGCT will benefit from adjuvant PC-RPLND.

Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy.

To investigate the impact of bleomycin-etoposide-carboplatin combination chemotherapy on long-term fertility in patients with testicular germ cell tumors. Twenty-five patients with high risk stage I and IM non-seminomatous germ cell tumors (NSGCT, Group A) and 44 with advanced seminoma or NSGCT (Group B) were treated with bleomycin 30 mg (days 2, 9, 16), etoposide 165 mg/m(2) (days 1-3) and carboplatin 400mg/m(2) or AUC 5 (day 1) (BEC(90)). Treatment was repeated every 3 weeks. Group A patients received 2 cycles of BEC(90), while Group B ones received 4 to 5 cycles of BEC(90). Sperm count and hormonal analyses were examined pre- and post-chemotherapy. Counts were classified as normospermia (NS) if >20 x 10(6)ml(-1), oligospermia (OS) if 1-20 x 10(6)ml(-1) and azoospermia (AS) if <1 x 10(6)ml(-1). Patients were followed for a median of 2.9 years post-chemotherapy. The post-orchidectomy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit while the serum levels of follicle stimulating hormone (FSH) and testosterone (T) were within the reference interval. Thirty-eight (55%) patients had NS pre-chemotherapy. None of the 14 NS patients who received 2 cycles of BEC(90) had AS post-chemotherapy, while only 1 of the 24 NS patients who were treated with > or =4 cycles of BEC(90) had AS post-treatment. Among the NS patients, 93% and 83%, respectively, remained NS following chemotherapy. Overall, 90% of patients had recovery (61% NS, 29% OS) of spermatogenesis after treatment. The median FSH serum values were significantly elevated at least 1-year post-chemotherapy when compared with the pre-treatment levels. Eighteen months post-chemotherapy the median FSH values had returned to the reference limits. Serum LH and T levels were unaffected by treatment. The pre-treatment sperm count and the bulk of disease were significantly associated with recovery of spermatogenesis. No association was found between recovery of spermatogenesis and 2 or > or =4 cycles of chemotherapy, age > or =30 years and post-chemotherapy lymph node dissection. Thirteen patients (4 with OS) fathered 16 children. No congenital abnormalities occurred in any of these children. The BEC(90) regimen has no major effect on fertility and Leydig cell function. However, carboplatin-based chemotherapy has been proved less effective than cisplatin-based chemotherapy and is not currently used in the treatment of testicular cancer.