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Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry was performed on 178 primary tumors and 126 lymph node metastases, eligible cases (moderate/strong, complete/incomplete membrane staining) were assessed by FISH. HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were associated with moderate/strong incomplete membrane staining that were not scored eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score cases, 67% were associated with HER2-positive FISH. Concordance between primary tumors and matched lymph node metastases was moderate for immunohistochemistry (κ = 0.54 (CI 95%, 0.41-0.67)) and FISH (κ = 0.50 (CI 95%, 0.20-0.79)). HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and carcinoma with squamous differentiation (11%) than in pure conventional carcinoma (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7% primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented intratumoral heterogeneity. Our study suggests that HER2 evaluation should include an immunohistochemistry screening step with eligibility for FISH including incomplete/complete and moderate/strong membrane staining. Spatial or temporal intratumoral heterogeneity prompts to perform evaluation on both tumor and lymph node, and for each histological variant observed.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales , Inmunohistoquímica/normas , Receptor ErbB-2/análisis , Neoplasias de la Vejiga Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/mortalidad , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Hibridación Fluorescente in Situ/normas , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
Purpose: Androgen deprivation therapy (ADT) may cause vasomotor symptoms (VMS) including hot flushes and sweats, which affect quality of life (QoL). Serelys Homme is a nonhormonal and a natural origin product that could affect VMS in men undergoing ADT. We evaluated effectiveness and tolerance of Serelys Homme administration on VMS and QoL of patients undergoing combined ADT and radiation therapy for prostate cancer. Methods and Materials: Between April 2017 and July 2019, 103 patients were screened, and 53 patients refused to participate in the study. Serelys Homme therapy consisted of a daily administration of 2 tablets for 6 months. Patients were evaluated with 4 questionnaires including the adapted Modified Rankin Scale (adapted-MRS), European Quality of Life 5 Dimensions 3 Level Version (EQ 5D3L), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Hot Flash Related Daily Interference Scale (HFRDIS) at day 0, day 90 (D90), and day 180 (D180). Statistical evaluation was performed using the Wilcoxon rank sign test. A 2-sided P < .05 was considered statistically significant. Results: Among the 50 patients, 4 withdrew after inclusion. All patients (n = 46) received either postoperative or definitive radiation therapy combined with a short (n = 15) or long course (n = 31) of ADT. Serelys Homme administration significantly decreased the rate of patients who had ≥7 VMS and 3 to 6 VMS per day. The number of patients presenting with moderate or severe VMS was decreased at D90 (P = .005) and at D180 (P = .005). In addition, VMS duration was reduced at D90 (P = .002) and D180 (P < .001). Finally, at D90 and D180, 11.1% and 16.0% of patients, respectively, with initial severe or moderate VMS had a complete response without further symptoms. Among QoL parameters, fatigue decreased significantly. Effectiveness evaluated by doctors was rated as moderate or good to excellent VMS control in 20% and 60% of the patients, respectively. No side effects were recorded in the whole population. Conclusions: This study demonstrated effectiveness and excellent tolerance of Serelys Homme. We observed a significant reduction of the frequency, duration, and intensity of hot flushes and sweats induced by ADT. Serelys Homme increased QoL scores. These encouraging results open the prospect to further studies and Serelys Homme use in patients undergoing ADT for prostate cancer.
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BACKGROUND: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.
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Recurrencia Local de Neoplasia/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Terapia Recuperativa , Resultado del TratamientoRESUMEN
The use of RNA-sequencing technologies held a promise of improved diagnostic tools based on comprehensive transcript sets. However, mining human transcriptome data for disease biomarkers in clinical specimens are restricted by the limited power of conventional reference-based protocols relying on unique and annotated transcripts. Here, we implemented a blind reference-free computational protocol, DE-kupl, to infer yet unreferenced RNA variations from total stranded RNA-sequencing datasets of tissue origin. As a bench test, this protocol was powered for detection of RNA subsequences embedded into putative long noncoding (lnc)RNAs expressed in prostate cancer. Through filtering of 1,179 candidates, we defined 21 lncRNAs that were further validated by NanoString for robust tumor-specific expression in 144 tissue specimens. Predictive modeling yielded a restricted probe panel enabling more than 90% of true-positive detections of cancer in an independent The Cancer Genome Atlas cohort. Remarkably, this clinical signature made of only nine unannotated lncRNAs largely outperformed PCA3, the only used prostate cancer lncRNA biomarker, in detection of high-risk tumors. This modular workflow is highly sensitive and can be applied to any pathology or clinical application.
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Neoplasias de la Próstata/genética , Análisis de Secuencia de ARN/métodos , Transcriptoma/genética , Biomarcadores de Tumor/genética , Estudios de Cohortes , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/diagnóstico , ARN Largo no Codificante/genética , Estudios RetrospectivosRESUMEN
INTRODUCTION: The IPSS (International Prostate Symptom Score), a structured self-administered questionnaire is the reference test for evaluation of lower urinary tract symptoms (LUTS). A 5-pictogram score entitled Score Visuel Prostatique en Images (SVPI) was proposed in France and evaluated by urologists. We assessed the interest of the SVPI for the identification and monitoring of benign prostatic hyperplasia (BPH)-related LUTS in general practice, and compared it with the IPSS. METHODS: A prospective observational survey was carried out with general practitioners (GPs) throughout France. The first 4consecutive patients aged over 60years, with BPH-related LUTS (IPSS score greater than 8) for whom the GP freely intended to prescribe an alpha-blocker, were enrolled. Two self-administered questionnaires were used at baseline and at follow-up visit (between 1 and 3months): French language version of the IPSS (8questions) and the SVPI. The 5pictograms of the SVPI were: How many times do you urinate during the day (score of 0 to 5)? How many times do you urinate during the night (score of 0 to 5)? Do you experience an urgent need to urinate (score of 0 to 4)? How strong is the stream (response from 0 to 4)? Do you urinate in a satisfactory manner (score of 0 to 6)? The primary objective was to assess and validate the sensitivity to change of the SVPI at baseline and follow-up visit by the study of the correlation of its changes according to the changes of LUTS evaluated with the IPSS. RESULTS: Five hundred and forty seven GPs enrolled at least one patient and returned information. 2261patients completed the inclusion questionnaire, and 1359 were included in the statistical analysis. Under treatment with alpha-blocker, the IPSS average decreased from 17.7±4.9 to 10.5±4.4 (P<0.0001) with an average diminution of 7.2±4.0, which corresponded to an improvement of 40.7%. This significant decrease of the IPSS involved all its components. The total SVPI was evaluated to 13.8±3.1, the irritative sub-score to 7.4±2.0, and the obstructive sub-score to 2.4±0.8. The internal consistency of the SVPI was good with a value of the Cronbach Alpha coefficient of 0.74. Under treatment with alpha-blocker, the value of the total SVPI decreased from 13.8±3.1 to 8.2±3.0 (P<0.0001) between enrolment and the follow-up visit. The Pearson coefficients assessing the correlations in 1359 patients with benign prostatic hypertrophy were statistically significant at enrolment, and at the follow-up visit. Their variations were all significant. The correlations were weak for the obstructive subscores. Four hundred and fifty-one GPs gave their opinion on the SVPI compared to IPSS: for 36.8% of them, the SVPI was completed a little more rapidly than the IPSS, for 34.6% more rapidly, and for 22.8% of them the SVPI was completed much more rapidly. For 5.8% of them, there was no difference. With regard to ease of understanding for the patient, the 451 GPs responded: much easier for 27.3%, easier for 37.3%, a little easier for 27.1%, and 8.4% had no opinion. CONCLUSION: This study showed the SVPI to be a simple and useful tool for identifying and monitoring BPH-related LUTS. Total SVPI was correlated with total IPSS, even if the obstructive subscore correlation was weaker. The good sensitivity of the SVPI to change showed its potential interest for monitoring LUTS. Given the underuse of the IPSS and the interest expressed by GPs and urologists, the SVPI might be used alone to analyse patient complaints.
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Autoevaluación Diagnóstica , Síntomas del Sistema Urinario Inferior/diagnóstico , Síntomas del Sistema Urinario Inferior/etiología , Hiperplasia Prostática/complicaciones , Anciano , Estudios de Seguimiento , Medicina General , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Evaluación de SíntomasRESUMEN
BACKGROUND: In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. RESULTS: The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. CONCLUSION: Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment.