Objective
This multi-institutional phase I/II trial explored patient-assessed tolerance of increasingly hypofractionated (HPFX) radiation for low/intermediate risk prostate cancer.
Methods
347 patients enrolled from 2002–2010. Three increasing dose-per-fraction schedules of 64.7 Gy/22 fx, 58.08 Gy/16 fx and 51.6 Gy/12 fx were each designed to yield equivalent predicted late toxicity. Three quality of life (QoL) surveys were administered prior to treatment and annually up to 3 years.
Results
Bowel QoL data at 3 years revealed no significant difference among regimens (p=0.469). Bowel QoL for all regimens declined transiently, largely recovering by three years, with only the 22 fraction decrement reaching significance. Bladder outcomes at 3-years were comparable (p=0.343) although, for all patients combined, a significant decline was observed from baseline (p=0.008). Spitzer quality of life data revealed similarly excellent, 3-year means (p=0.188). International erectile function data also revealed no significant differences at 3 years although all measures except intercourse satisfaction worsened post-treatment.
Conclusions
Three-year QoL changes for bowel, bladder and SQLI were modest and similar for 3 HPFX regimens spanning 2.94–4.3 Gy per fraction. These favorable patient-scored outcomes demonstrate the safety and tolerability of such regimens and may be leveraged to support further implementation of mild to moderately hypofractionated radiotherapy in the setting of low and intermediate-risk prostate cancer
samples were located) did not have metastases at diagnosis and did not develop distant recurrence, both of which were over-represented in the other 3 clusters. Kaplan-Meier analysis revealed a trend towards longer overall survival in cluster 1 patients (log rank p Z 0.065). Higher gene expression of PRC1, NCAM1 (CD56) and DLL3 correlated with higher SC%, as did lower gene expression of ERBB2, PD-L1 and HPGD (p < 0.01). PD-L1 protein expression determined by IHC (1% cells) was noted in 30% of patients but did not correlate with outcome, SC%, DLL3 protein expression (IHC), or PD-L1 gene expression. DLL3 protein expression (1% cells) was noted in 68% of patients and DLL3 > 10% correlated with decreased OS (p Z 0.03). Higher DLL3 protein expression correlated with DLL3 gene expression (Spearman r Z 0.70, p < .01) and with SC% (r Z 0.33, p Z 0.01). Conclusion: This is the first study to reveal distinct gene expression patterns that define aggressive behavior, metastatic potential and outcomes in SCBC. The prognostic value of differential gene expression networks and the presence of underlying genetic and epigenetic alterations is the subject of ongoing prospective validation in a larger cohort.
subgroups (HR 1.7, 95% CI 1.0-2.8, p Z 0.033). In high-risk subgroups, 5year BCR-free survival rates of patients with PSA level < 0.50 and 0.50 ng/ml at BCR were 45% (95% CI, 34e55) and 28% (95% CI, 14e44), respectively (p Z 0.033). Early SRT did not improve outcomes significantly in low-and intermediate-risk groups (p Z 0.92 and 0.85, respectively). Conclusion: This study suggested that early SRT is beneficial only for selected high-risk subgroups of patients affected by BCR after RP.
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