A nomogram including baseline prognostic factors to estimate the activity of second‐line therapy for advanced urothelial carcinoma

Abstract

ObjectiveTo study the impact of the prognostic factors liver metastasis (LM), anaemia (haemoglobin [Hb] <10 g/dL), Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥1 and time from previous chemotherapy (TFPC) on the activity of second-line therapy for advanced urothelial carcinoma (UC). Patients and MethodsTwelve phase II trials evaluating second-line chemotherapy and/or biological characteristics (n = 748) in patients with progressive disease were pooled.Progression-free survival (PFS) was defined as tumour progression or death from any cause.The PFS rate at 6 months (PFS6) was defined from the date of registration and calculated using the Kaplan-Meier method.Response rate (RR) was defined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.0.A nomogram predicting PFS6 was constructed using the RMS software package in R (http://www.r-project.org). ResultsData regarding progression, anaemia, LM, ECOG-PS and TFPC were available from 570 patients in nine phase II trials.The overall median PFS was 2.7 months, PFS6 was 22.2% (95% confidence interval 18.8-25.9) and the RR was 17.5% (95% CI: 14.5-20.9%).For every unit increase in risk group, the hazard of progression in 6 months increased by 41% and the odds of response decreased by 48%.A nomogram was constructed to predict PFS6 on an individual patient level.The model was internally validated and was shown to have acceptable calibration performance. ConclusionsThe RR and PFS6 vary as a function of baseline prognostic factors in patients receiving second-line therapy for advanced UC.

Complete Response as an Intermediate End Point in Patients Receiving Salvage Systemic Therapy for Urothelial Carcinoma

“…Despite the caveats of the small number of CR patients, it is notable that the CR patients did not cluster in the good risk group as defined by all of the 4 previously recognized prognostic factors (PS, Hb, LM, and TFPC) because these 4 factors have been found to be associated with the activity of salvage therapy as defined by overall response and PFS at 6 months, in addition to survival. 19,22,23 More intriguingly, CR with salvage therapy was not clearly associated with previous CR; indeed, only 1 of the 7 patients with prior response data available had displayed prior CR, and 3 had displayed progressive disease as the best prior response. While the ability to undergo previous cisplatin-based chemotherapy and longer TFPC may select for favorable host and tumor biology, these findings suggest that molecular factors associated with response to specific agents may be the driver of CR.…”

Survival prediction models for patients with anal carcinoma receiving definitive chemoradiation: A population‑based study

“…Although the classical TNM staging system is widely used in the clinical setting, the survival outcome of patients with cancer is not only influenced by the tumor itself. Additional factors, including age, sex and therapeutic strategies, may affect the prognosis of patients with certain types of cancer, including urothelial carcinoma (37). The development of nomograms, which are practical and convenient tools that evaluate the survival probability of a specific outcome, and include large influential factors and easily available and measurable parameters, could successfully overcome the disadvantages of the conventional TNM staging system (38,39).…”

Future Directions and Targeted Therapies in Bladder Cancer

“…94 In addition, prognostic factors (liver metastasis, hemoglobin level, performance status, time from prior chemotherapy) affect both activity and long-term outcomes; hence, a nomogram to compare expected versus observed outcomes using PFS at 6 months as a more optimal, universally applicable intermediate end point across cytotoxic and biologic agents may facilitate the interpretation of phase II salvage trials. [95][96][97][98] A more focused biomarker-enriched phase II design using a high threshold of activity of interest warrants consideration rather than phase III trials.…”