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Grunewald CM , Henn A , Galsky MD , Plimack ER , Harshman LC , Yu EY , Crabb SJ , Pal SK , Alva AS , Powles T , De Giorgi U , Agarwal N , Bamias A , Ladoire S , Necchi A , Vaishampayan UN , Sternberg CN , Bellmunt J , Baniel J , Niegisch G
Impact of timing of adjuvant chemotherapy following radical cystectomy for bladder cancer on patient survival
Urol Oncol. 2020 Jul 10;38(12) :934 e1-934 e9
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Abstract
BACKGROUND: Trials of adjuvant chemotherapy following radical cystectomy generally require chemotherapy to start within 90 days postoperatively. However, it is unclear, whether the interval between surgery and start of adjuvant therapy (S-AC-interval) impacts the oncological outcome. METHODS: Using the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) data base, we identified patients who underwent radical cystectomy for muscle invasive bladder cancer and subsequent adjuvant chemotherapy. Univariate analysis of patient characteristics, surgical factors and tumor characteristics regarding their impact on S-AC-interval was performed using Kruskal-Wallis testing and Fisher's exact test. Analysis of progression-free (PFS) and overall survival (OS) (follow-up time beginning with the start date of adjuvant chemotherapy) was analyzed in relation to S-AC-interval (continuous and dichotomous with a cut-off at 90 days) using Kaplan-Meier method and COX regression analysis. RESULTS: We identified 238 eligible patients (83.5% male, mean age: 63.4 years, 76.1% T3/T4, 66.4% pN+, 14.7% R+, 70.6% urothelial carcinoma, 71% cisplatin-based adjuvant chemotherapy). The majority of patients (n = 207, 87%) started chemotherapy within 90 days after surgery. Median S-AC-interval was 57 days (interquartile range 32.8). S-AC-interval did not have consistent association with any patient/tumor characteristics or surgery related factors (type of surgery, urinary diversion). Survival analysis using continuous S-AC-interval revealed a trend toward an impact of S-AC-interval on OS (hazard ratio 1.004, 95% confidence ratio 0.9997-1.0084, P = 0.071). With regards to PFS, that impact was shown to be statistically significant (hazard ratio 1.004, 95% confidence ratio 1.0003-1.0075, P = 0.032). In multivariate analysis, however, S-AC-interval was negated by tumor and patient related factors (pathological T-stage, N-stage, ECOG performance status). Accounting for eligibility criteria defined in some clinical trials, we extended our analysis dividing S-AC-interval in ≤90 and >90 days. Although we could confirm the trend toward better outcome in patients with a shorter S-AC interval in dichotomous analysis, neither differences in OS nor in PFS reached statistical significance (P = 0.438 and P = 0.056). CONCLUSIONS: In a large multi-institutional experience, 87% of patients who received adjuvant chemotherapy received it within the guideline recommended window of 90 days. While it was not possible to determine whether this is the optimal cut-off, early start of adjuvant chemotherapy seems to be reasonable. Regarding prognosis, tumor-related pathological factors abrogated the importance of the S-AC-interval in our analysis.
Notes
1873-2496 Grunewald, Camilla M Henn, Alina Galsky, Matthew D Plimack, Elizabeth R Harshman, Lauren C Yu, Evan Y Crabb, Simon J Pal, Sumanta K Alva, Ajjai Shivaram Powles, Thomas De Giorgi, Ugo Agarwal, Neeraj Bamias, Aristotelis Ladoire, Sylvain Necchi, Andrea Vaishampayan, Ulka N Sternberg, Cora N Bellmunt, Joaquim Baniel, Jack Niegisch, Guenter Journal Article United States Urol Oncol. 2020 Dec;38(12):934.e1-934.e9. doi: 10.1016/j.urolonc.2020.06.008. Epub 2020 Jul 10.