Prognostic factors in prostate cancer

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma : a Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy

Background: We tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM. Results: Of all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: 123.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5). Conclusion: Surveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other. Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients, who underwent respectively surveillance (40%), chemotherapy (CHT; 8%), or radiotherapy (RT; 52%) after orchiectomy. Surveillance and CHT rates increased over time, whereas RT rates decreased. A protective effect of active treatment defined as either RT or CHT was identified on cancer-specific mortality, relative to surveillance

Nivolumab + ipilimumab (NIVO + IPI) adjuvant versus placebo dans le carcinome rénal localisé à haut risque de récidive après néphrectomie : résultats de l’étude de phase 3 randomisée Checkmate 914 (CM914)

Objectifs NIVO + IPI a démontré une amélioration de la survie globale versus sunitinib dans le CCR métastatique (NEJM2018 ;378 :1277–90). CM914, est une étude de phase 3, randomisée, en double aveugle, multicentrique, évaluant NIVO + IPI versus placebo (partie-A) ou NIVO monothérapie versus NIVO + IPI versus placebo (partie-B), chez des patients atteints de CCR localisé à haut risque de récidive après néphrectomie. Nous rapportons ici la première analyse de la partie-A. Méthodes Les critères d’inclusion principaux comportent : néphrectomie radicale ou partielle avec marges chirurgicales négatives, composante à cellules claires prédominante, pT2a (G3-4) N0M0, pT2b/pT3(a,b,c)/pT4 (tout grade) N0M0, ou pT0-4 (tout G) N1M0 ; sans signe de maladie résiduelle ou métastases. Les patients étaient randomisés 1 :1 sous NIVO 240 mg/2 semaines (×12) + IPI 1 mg/kg/6 semaines (×4) ou placebo, avec stratification selon stade TNM et type de néphrectomie ; durée de traitement de 24 semaines ou jusqu’à récidive/toxicité inacceptable. Le critère d’évaluation principal était la survie sans maladie (DFS) en revue centralisée (BICR). La survie globale et la tolérance étaient des objectifs secondaires. Résultats L’inclusion des patients dans la partie-A a commencé en juillet 2017 et s’est terminée en février 2021. L’analyse finale de la DFS par le BICR et les objectifs secondaires disponibles sera présentée pour les 800 patients randomisés dans le bras NIVO + IPI ou placebo dans la partie-A de l’étude CM914. Au total, environ 227 événements de DFS parmi les patients randomisés dans la partie-A sont attendus, assurant une puissance de 90 % pour détecter un hazard ratio de 0,65 avec un risque global d’erreur de type I de 0,05 (bilatérale). Conclusion Ces résultats devraient soutenir le rôle de NIVO + IPI en tant que nouvelle option d’immunothérapie adjuvante pour les patients atteints de carcinome rénal localisé présentant un risque élevé de récidive post-néphrectomie