Background: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. Methods: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. Results: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). Conclusion: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5 year-recurrence rate of almost 40%.

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? : results of a comprehensive analysis based on the multicenter CORONA database / I., Wolff; M., May; B., Hoschke; R., Zigeuner; L., Cindolo; G., Hutterer; L., Schips; O., De Cobelli; Rocco, Bernardo Maria Cesare; C., De Nunzio; A., Tubaro; I., Coman; B., Feciche; M., Truss; O., Dalpiaz; R., Figenshau; K., Madison; M., Sánchez Chapado; M., Santiago Martin; L., Salzano; G., Lotrecchiano; S., Shariat; M., Hohenfellner; R., Waidelich; C., Stief; K., Miller; S., Pahernik; S., Brookman May. - In: EUROPEAN JOURNAL OF SURGICAL ONCOLOGY. - ISSN 0748-7983. - 42:5(2016), pp. 744-750. [10.1016/j.ejso.2016.01.009]

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? : results of a comprehensive analysis based on the multicenter CORONA database

ROCCO, Bernardo Maria Cesare;
2016

Abstract

Background: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. Methods: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. Results: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). Conclusion: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5 year-recurrence rate of almost 40%.
22-gen-2016
42
5
744
750
Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? : results of a comprehensive analysis based on the multicenter CORONA database / I., Wolff; M., May; B., Hoschke; R., Zigeuner; L., Cindolo; G., Hutterer; L., Schips; O., De Cobelli; Rocco, Bernardo Maria Cesare; C., De Nunzio; A., Tubaro; I., Coman; B., Feciche; M., Truss; O., Dalpiaz; R., Figenshau; K., Madison; M., Sánchez Chapado; M., Santiago Martin; L., Salzano; G., Lotrecchiano; S., Shariat; M., Hohenfellner; R., Waidelich; C., Stief; K., Miller; S., Pahernik; S., Brookman May. - In: EUROPEAN JOURNAL OF SURGICAL ONCOLOGY. - ISSN 0748-7983. - 42:5(2016), pp. 744-750. [10.1016/j.ejso.2016.01.009]
I., Wolff; M., May; B., Hoschke; R., Zigeuner; L., Cindolo; G., Hutterer; L., Schips; O., De Cobelli; Rocco, Bernardo Maria Cesare; C., De Nunzio; A., Tubaro; I., Coman; B., Feciche; M., Truss; O., Dalpiaz; R., Figenshau; K., Madison; M., Sánchez Chapado; M., Santiago Martin; L., Salzano; G., Lotrecchiano; S., Shariat; M., Hohenfellner; R., Waidelich; C., Stief; K., Miller; S., Pahernik; S., Brookman May
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0748798316000512-main.pdf

non disponibili

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 370.63 kB
Formato Adobe PDF
370.63 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1128572
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 28
social impact