br Association of TSG alterations and clinical outcomes br Fig

3.2. Association of TSG alterations and clinical outcomes
Fig. 1 – Localized disease: Kaplan-Meier curves for (A) event-free survival and (B) time to CRPC, by TSG alteration and unique gene hits (monoallelic/ biallelic). Biomarker positive indicates any TSG alteration. CI = confidence interval; CRPC = castration-resistant prostate cancer; CSPC = castration-sensitive prostate cancer; HR = hazard ratio; Rx = recurrence; TSG = tumor suppressor gene.
Median follow-up in the M1-CRPC cohort was 4.1 yr. The median duration of first-line CRPC therapy was short at 6 mo (interquartile range 3–10 mo), with the majority of patients (64%) receiving first-line AR-directed therapy (conventional nonsteroidal antiandrogen: 35%; abirater-one: 19%; enzalutamide: 10%). While the study was not powered to detect Spectinomycin significant difference in OS in the M1-CRPC cohort, there was evidence of an increased risk of death with TSG-alt (median OS: 4.5 yr, HR 3.26, 95% CI 0.43–24.72, p = 0.23) and cumulative gene hits (log rank
Table 3 – Time to event analyses by TSG alteration and unique gene hits (monoallelic/biallelic)
EFS N (events)
TSG altered
Unique gene hits
TTCRPC N (events)
Median TTCRPC HR (95% CI) p value
TSG altered
Unique gene hits
OS N (events)
TSG altered
Unique gene hits
M1-CSPC
TTCRPC N (events)
Median TTCRPC HR (95% CI) p value
TSG altered
Unique gene hits
M1-CSPC
OS N (events)
TSG altered
Unique gene hits
M1-CRPC
Duration of first-line CRPC therapy N (events) Median duration (mo), (95% CI) HR (95% CI) p value
TSG altered
No
Yes
Unique gene hits
Table 3 (Continued )
M1-CRPC
Duration of first-line CRPC therapy N (events) Median duration (mo), (95% CI) HR (95% CI) p value
M1-CRPC
TSG altered
Unique gene hits
CI = confidence interval; CRPC = castration-resistant prostate cancer; EFS = event-free survival; HR = hazard ratio; L-CSPC = localized castration-sensitive prostate cancer; M1-CRPC = metastatic castration-resistant prostate cancer; M1-CSPC = metastatic castration-sensitive prostate cancer; NA = not reached the median time yet; NE = not evaluable due to zero]FID$T1[or few events in a group; OS = overall survival; TTCRPC = time to castration-resistant prostate cancer; TSG = tumor suppressor gene.
Fig. 2 – Metastatic hormone-sensitive disease: Kaplan-Meier curves for (A) time to CRPC and (B) overall survival, by TSG-alt and unique gene hits (monoallelic/ biallelic). Biomarker positive indicates any TSG alteration. ADT = androgen deprivation therapy; CI = confidence interval; CRPC = castration-resistant prostate cancer; CSPC = castration-sensitive prostate cancer; HR = hazard ratio; NE = not evaluable; TSG = tumor suppressor gene; TSG-alt = TSG altered.
Fig. 3 – Metastatic castration-resistant disease: Kaplan-Meier curves for overall survival by TSG-alt and unique gene hits (monoallelic/biallelic). Biomarker positive indicates any TSG alteration. CI = confidence interval; CRPC = castration-resistant prostate cancer; HR = hazard ratio; NE = not evaluable; TSG = tumor suppressor gene; TSG-alt = TSG altered.
only (Supplementary Table 5). Notably, of the four (8%) men who were TSG unaltered, only one died at 5.2 yr after the diagnosis of CRPC. Multivariate analyses of OS in the metastatic cohorts are included in the Supplementary material (Supplementary Table 7).
To validate the association of TSG alterations and risk of relapse in L-CSPC, we analyzed a cohort of localized prostate cancer [2] (n = 157) profiled for copy number alterations by array comparative genomic hybridization (and for PTEN and TP53 mutations by exon sequencing in a subset). The distribution of TSG alterations (monoallelic/biallelic) was similar to the DFCI cohort (Supplementary Table 8). Forty-four percent had TSG-alt, and 14% harbored two or more TSG hits. Increasing gene hits were significantly associated with relapse (disease-free survival: log rank p < 0.001; TSG1 vs TSG0, HR 1.09, 95% CI 0.50–2.36; TSG2–3 vs TSG0, HR 3.93, 95% CI 1.87–8.24; Supplementary Fig. 3).