Impact of early palliative care on additional line of chemotherapy in metastatic breast cancer patients: results from the randomized study OSS.

PURPOSE: The most appropriate criteria and timing for palliative care referral remain a critical issue, especially in patients with metastatic breast cancer for whom long-term chemosensibility and survival are observed. We aimed to compare the impact of early palliative care including formal concertation with oncologists on decision for an additional line of chemotherapy compared with usual oncology care. METHODS: This randomized prospective study enrolled adult women with metastatic breast cancer and visceral metastases with a 3rd- or 4th-line chemotherapy (CT). Patients received usual oncology care with a palliative care consultation only upon patient or oncologist request (standard group, S) or were referred to systematic palliative care consultation including a regular concertation between palliative care team and oncologists (early palliative care group, EPC). The primary endpoint was the rate of an additional CT (4th or 5th line) decision. Quality of life, symptoms, social support and satisfaction were self-evaluated at 6 and 12 months, at treatment discontinuation or 3 months after discontinuation. RESULTS: From January 2009 to November 2012, two authorized cancer centers included 98 women (EPC: 50; S: 48). Thirty-seven (77.1%, 95%CI 62.7-88%) patients in the EPC group had a subsequent chemotherapy prescribed and 36 (72.0%, 95%CI 57.5-83.8%) in the S group (p = 0.646). No differences in symptom control and global quality of life were observed, but less deterioration in physical functioning was reported in EPC (EPC: 0 [- 53-40]; S: - 6; 7 [- 60 to - 20]; p = 0.027). Information exchange and communication were significant improved in EPC (exchange, EPC: - 8.3 [- 30 to + 7]; S: 0.0 [- 17 to + 23]; p = 0.024; communication, EPC: 12.5 [- 8 to - 37]; S: 0.0 [- 21 to + 17]; p = 0.004). CONCLUSION: EPC in metastatic breast cancer patients did not impact the prescription rate of additional chemotherapy in patients a 3rd- or 4th-line chemotherapy for metastatic breast cancer; however, EPC may contribute to alleviate deterioration in physical functioning, while facilitating communication. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT00905281, May 20, 2009.

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial.

BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0.54, 95% CI 0.4-0.73, p<0.0001), with 5-year progression-free survival of 47.6% (95% CI 38.8-55.9) in the immediate treatment group and 31.8% (24.2-39.6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. INTERPRETATION: Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING: Lilly, Canadian Cancer Society Research.

A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer.

BACKGROUND: The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. METHODS: Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. RESULTS: In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.

Different outcome of invasive cervical cancer associated with high-risk versus intermediate-risk HPV genotype.

Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety-six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High-risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p = 0.009), tumour size (p = 0.01) and HPV status (p = 0.02) were associated with disease-free survival (median follow-up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31, 33, 35, 39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p = 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes.

Urokinase-type plasminogen activator and plasminogen-activator-inhibitor type 1 predict metastases in good prognosis breast cancer patients.

UNLABELLED: This retrospective analysis was designed to confirm the predictive role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type I (PAI-1) in the outcome of early stage, node-negative breast cancer patients. PATIENTS AND METHODS: Node-negative patients having not received adjuvant chemotherapy, and for whom frozen samples were available, were selected. RESULTS: Among the 169 patients included, 56.8% presented with uPA >3 ng/mg of proteins and/or PAI-1 >14 ng/mg of proteins. The median follow-up was 73 months. Significant correlations were found between uPA and disease-free survival (p [univariate]=0.003; p [multivariate]=0.01), and between uPA, PAI-1, and uPA plus PAI-1 and distant relapses (p=0.002). No significant correlation was found between uPA/PAI-1 and the risk of locoregional recurrence. CONCLUSION: This study demonstrated that uPA and PAI-1 are useful predictors of distant metastases in a subset of early stage, node-negative breast cancer patients.

Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse.

PURPOSE: Clinical significance of disseminated tumor cells (DTC) in bone marrow of early breast cancer patients has been reported, but improvements in detection methods are needed. EXPERIMENTAL DESIGN: Bone marrow aspirates from 621 patients with stage I to III breast cancer were screened for cytokeratin-positive (CK+) cells. CK+ cells were categorized into DTC only if they had specific morphologic features of tumor cells. Bone marrow status and clinical and pathologic variables of the patients were correlated with clinical outcome after a median follow-up of 56 months. RESULTS: DTC and non-DTC CK+ cells were detected in 15% and 34% of patients, respectively, with no correlation with clinical and pathologic variables. On univariate analysis, DTC detection was associated with a poorer distant metastasis-free survival (DMFS; P = 0.0013) and overall survival (OS; P = 0.005). Moreover, DTC detection was also associated with local relapse-free survival (P = 0.0009). On multivariate analysis, DTC detection was an independent prognostic factor for DMFS, local relapse-free survival, and OS. There was no significant interaction between DTC detection and hormonal receptors status (P = 0.34). Non-DTC CK+ cells had no clinical significance. CONCLUSION: DTC detection is a powerful prognostic marker for DMFS and OS in early breast cancer patients and can be individualized from irrelevant non-DTC CK+ cells by morphologic criteria. Biologically, despite high rates of systemic adjuvant therapy and locoregional irradiation in this series, DTC detection remains a prognostic factor of distant and, more strikingly, of local relapse, in favor of resistance to treatment of locally or distant disseminated cancer cells in DTC-positive patients.

Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients?

BACKGROUND: This study was performed to describe the treatment plan modifications after a geriatric oncology clinic. Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center. PATIENTS AND METHODS: Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included. Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed. Oncology data and treatment decisions were recorded before and after this consultation. Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan. RESULTS: Patient characteristics included a median age of 79 years and a predominance of women with breast cancer. About one half of patients had an independent functional status. Nearly 15% presented severe undernourishment. Depression was suspected in 53.1% of cases. One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications. Of the 93 patients with an initial treatment decision, the treatment plan was modified for 38.7% of cases after this assessment. Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan. CONCLUSION: The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases. Further studies are needed to determine whether these modifications improve the outcome of these older patients.

[Cancer of the breast and pregnancy: the point of view of the breast cancer specialist]. / Cancer du sein et grossesse: le point de vue du sénologue.

Breast cancer is the most common cancer in pregnant women occurring in about 1 in 3,000 pregnancies; the engorgement of the breasts in this period may hinder detection of masses and delays in diagnosis are common; this delay, the young age can explain that overall survival of pregnant women is generally worse than in nonpregnant women. In early stage cancer surgery is recommended as the primary treatment; radiation must be avoided during this period but chemotherapy, if considered necessary, specially in late stage disease, may be given after the first trimester without risk of fetal malformation; termination of pregnancy has not been shown to have any beneficial effect but may be considered if maternal treatments are limited by continuation of pregnancy. In contrast, pregnancy in patients with a prior history of breast cancer does not appear compromise the survival of women and no deleterious effects have not been demonstrated in the fetus: if a risk of relapse exists for the breast carcinoma, it's recommended that patients wait two or three years after diagnosis before attempting to conceive.

Risk of breast cancer by individual insulin use: an international multicenter study.

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.

[Survival of breast cancers patients with meningeal carcinoma]. / Méningites carcinomateuses des cancers du sein.

PURPOSE: Among all solid tumors breast cancer is the most common cause of meningeal carcinomatosis (MC). The purpose of this study was to analyze clinical and biological responses as well as overall survival in MC patients (pts) of breast primary treated with intrathecal methotrexate (MTX). METHODS AND MATERIALS: Single-center retrospective series of MC pts treated between 2000 and 2007. Chemotherapy regimen was: MTX (15 mg/day; day 1-5) and depomedrol (40 mg, day 1) plus leucoverin (12 mg IV or 25 mg PO; day 1-5). Treatment cycles were repeated every 2 weeks. The survival was analyzed according to the characteristics of the tumor considering clinical and cytological response rates to treatment. RESULTS: The median survival was 4.5 months (range 0-53). In multivariate analysis, poor prognostic factors at diagnosis were: Performans status greater than 2 [P = 0.006, RR = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra-21-1 level [P = 0.048, RR = 0.09-0.99]. The clinical progression after one cycle and the biological response after two cycles were independently correlated with OS [P<0.001, RR = 0.09 (0.02­0.37) and P = 0.003, RR = 3.6 (1.5­8.5), respectively]. A prognostic score designed to define three groups of patients is proposed. CONCLUSION: Although prognosis of patients with MC is poor, 1-year overall survival rate is 25%. The proposed prognostic score may be helpful in decision but warrants further assessment and validation in prospective trials.

[Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience]. / Métastases cérébrales dans les cancers du sein. Épidémiologie et histoire naturelle. Expérience de l'Institut Curie à travers deux études : les patientes HER2- de moins de 65 ans et les patientes de plus de 65 ans.

Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.

Gemcitabine or gemcitabine plus oxaliplatin in the first-line treatment of patients with advanced transitional cell carcinoma of the urothelium unfit for cisplatin-based chemotherapy: a randomized phase 2 study of the French Genitourinary Tumor Group (GETUG V01).

BACKGROUND: The optimal chemotherapy for patients with advanced transitional cell carcinoma of the urothelium who are not eligible for cisplatin remains to be defined. OBJECTIVE: To assess the activity of gemcitabine alone (GEM) or in combination with oxaliplatin (GEMOX) in a randomized phase 2 trial. DESIGN, SETTING, AND PARTICIPANTS: The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors criteria. The sample size was based on a two-stage Fleming design with p0=35% and p1=55%. At the end of the first stage designed to register 20 patients on each treatment arm, the observation of seven or more objective responses would have led to the inclusion of 30 more patients in each arm. RESULTS AND LIMITATIONS: From July 2004 to March 2009, 44 patients in 10 centers were randomly assigned into the GEM or the GEMOX arm, 22 on each treatment arm. The median age was 76 yr. Seven patients were included for a performance status (PS) of 2 only. The remaining 37 patients had an impaired renal function, 11 of whom also had a PS of 2. The median creatinine clearance was 45 ml/min (range: 30-80 ml/min). The trial was closed after the first part because the GEMOX arm did not reach the targeted objective response rate to proceed further. CONCLUSIONS: Oxaliplatin does not add any significant activity (in terms of response rates) compared with gemcitabine alone in patients with advanced transitional cell carcinoma of the urothelium who are ineligible for cisplatin.

Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis.

KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.

Time to metastatic relapse and breast cancer cells dissemination in bone marrow at metastatic relapse.

Breast cancer dissemination can be monitored in patients by detecting circulating and/or disseminated tumor cells. However, bone marrow disseminated tumor cells (BM DTC) may undergo a dormancy during several years before growing (or not) into clinically detectable metastases. We therefore hypothesized that breast cancers which have formed BM DTC in the course of their metastatic growth might exhibit a longer interval before metastatic relapse. We examined the association of DTC detection (cytokeratin 8, 18 or 19 positive epithelial cells with cancerous morphological features), at metastatic relapse, with the metastasis-free interval in breast cancer patients. In the 110 metastatic patients studied, 42% (n = 64/110) were classified as BM DTC-negative. These patients had a significantly shorter metastasis-free interval than BM DTC-positive patients (P = 0.02). In multivariate logistic regression analysis, the metastasis-free interval was an independent predictor of DTC detection (P = 0.02), together with bone metastasis (P = 0.0003) and low tumor grade (grade I or II, P = 0.05). We finally suggest that a faster metastatic process might skip in some patients the BM DTC-associated dormancy step. Dissemination of DTC in other host organ and/or epithelial-mesenchymal transition from cytokeratin-positive to cytokeratin-negative DTC may explain this observation.

Pre-operative Concomitant Radio-chemotherapy in Bulky Carcinoma of the Cervix: A Single Institution Study.

OBJECTIVE: To evaluate the treatment results of patients (pts) with FIGO stage IB2, IIA, IIB cervical carcinoma (CC) treated with pre-operative radio-chemotherapy, followed by extended radical hysterectomy. METHODS: Retrospective study of 148 women treated to the Institut Curie for operable FIGO Stage IB2 to IIB, biopsy proved CC. Among them, 70 pts, median age 46 years, were treated using the same regimen associating primary radio-cisplatinum based chemotherapy, intracavitary LDR brachytherapy, followed by extended radical hysterectomy. Kaplan-Meier estimates were used to draw survival curves. Comparisons of survival distribution were assessed by the log-rank test. RESULTS: Complete histological local-regional response was obtained in 56% of the pts (n = 39). Residual macroscopic or microscopic disease in the cervix was observed in 28 pts (40%). All but one had in-situ microscopic residual CC. Lateral residual disease in the parametria was also present in 9 pts, all with residual CC. Pelvic lymph nodes were free from microscopic disease in 56 pts (80%). Eight of 55 (11%) radiological N0 patients had microscopic nodal involvement, as compared to 6/15 (40%) radiological N1 (p = 0.03). Seventeen pts (25%) had residual cervix disease but negative nodes. After median follow-up of 40 months (range, 8-141), 38/70 patients (54.1%) are still alive and free of disease, 6 (8.6%) alive with disease, and 11 (15.8%) patients were lost for follow-up but free of disease. IN CONCLUSION: The treatment of locally advanced CC needs a new multidisciplinary diagnostic and treatment approach using new therapeutic arms to improve the survival and treatment tolerance among women presenting this disease.

[Trastuzumab (Herceptin) and breast cancer: mechanisms of resistance]. / Trastuzumab (Herceptin) et cancer du sein: mécanismes de résistance.

The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. The mechanism of trastuzumab action is not fully understood but has been related to cell cycle inhibition. As to mechanisms of resistance, little is known but many preclinical data raised different hypothesis. Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.

[Oxaliplatin and ovarian cancer]. / Oxaliplatine et cancers de l'ovaire.

Oxaliplatin was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumor activity observed in experimental models resistant to cisplatin. As single agent at 130 mg/m2 every 3 weeks, the objective response rates rage from 16% to 29% in patients treated after failure of one or two regimens. As first line, in a randomized trial cyclophosphamide-cisplatin versus cyclophosphamide-oxaliplatine, no significant statistical differences were observed in efficacy parameters (response rate, progression free survival and overall survival). The toxicity profile seemed to favor the oxaliplatin arm. Many associations with other available active drugs as taxanes, gemcitabine and liposomal doxorubicin were performed with promising results.

After cystectomy, is it justified to perform a bladder replacement for patients with lymph node positive bladder cancer?

PURPOSE: After cystectomy for bladder cancer, when pelvic lymph nodes are positive, bladder replacement remains controversial. The aim of this study was to evaluate the outcome of patients who underwent neobladder replacement despite bladder cancer metastasis to the regional lymph nodes. MATERIALS AND METHODS: From 1981 to 1997, a total of 504 consecutive cystectomies for bladder cancer were performed at our institution. For 150 patients, pelvic lymphadenectomy were positive, nevertheless 71 patients underwent a neobladder replacement (50 N1 and 21 N2). The distribution of patients by clinical stage, according to the TNM 97 classification, was 4 T1, 14 T2, 32 T3 and 21 T4. No patient showed signs of metastasis on diagnosis. RESULTS: Five-year disease specific survival rate of the entire group (71 patients) was 46%. With a mean follow-up of 8.3 years (3.2-20 years), 25 patients (35%) were alive and free of disease (72% with day continence), five patients were alive with recurrence (three bone metastasis, one chest metastasis and one with local recurrence), 41 patients died, (three non-cystectomy related). Of the 46 patients who recurred, a total of eight patients had local recurrence. For five patients, a severe dysfunction of the plasty appeared: two needed definitive bladder drainage until they died, one patient became totally incontinent, one patient needed a conversion of the plasty to Bricker ileal conduit. For the remaining patient the tumor involvement provoked recto-plasty-cutaneous fistula. All these five patients died in the 6 months after the plasty dysfunction appeared. CONCLUSIONS: Although prognosis in bladder cancer metastasis to the regional lymph nodes has been reported to be poor, this study demonstrates that after cystectomy, it is justified to propose a neobladder replacement to well selected patients. Local recurrence only occurred in 11% of patients and there was no damage to enteroplasty function for nearly half of the patients, and considering benefit to the quality of life, orthotopic bladder substitution should be considered as the preferential diversion in this patient population.