Keywords:
Outcomes, Radiation therapy / Oncology, Cone beam CT, Oncology, Genital / Reproductive system male, Radiotherapy techniques
Authors:
S. Chin, A. Fatimilehin, R. Walshaw, H. Mistry, T. Elliot, J. Logue, J. Wylie, A. Choudhury; Manchester/UK
DOI:
10.26044/ranzcr2019/R-0109
Methods and materials
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A retrospective review of patient outcomes was performed on medical records for patients treated at one centre with curative intent radiotherapy to the prostate bed after RP for prostate adenocarcinoma between 2007 and 2009 with pT2-4N0M0 R0-1 histopathology. Exclusion criteria included patients treated with elective pelvic nodal radiotherapy. Local institutional approval was obtained for the study. Data was collected from January to February 2019.
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Patients were treated with 52.5Gy in 20 fractions over 4 weeks using a 4 field 3D conformal technique, undergoing CT simulation with volumes contoured according to the RADICALS trial protocol [3]. Patients underwent simulation and were treated with an empty bladder, and image guidance consisted of cone beam CT during days 1-3 and then weekly. Clinical management including the use of androgen deprivation therapy (ADT) was at the discretion of treating clinicians.
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SRT was defined as RT for a post-operative nadir PSA ≥0.10 ng/mL or rising post-operative PSA. Early SRT was defined as RT commencing at a pre-RT PSA of ≤0.2 ng/mL.
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The study outcomes were post RT freedom from biochemical failure (FFBF), distant metastasis (DM), cancer specific mortality (CSM) and overall survival (OS). BF was defined as a PSA ≥0.4 ng/mL and rising after RT or by the commencement of salvage ADT after SRT. PSA was collected according to physician discretion, generally every 6-12 months. DM events were defined as radiographic or histological evidence of metastases from prostate cancer. CSM events were defined as any deaths occurring with progressive disease on secondary therapies, as a result of adverse effects from prostate cancer–directed therapy or with documented death from prostate cancer. OS events were defined as death from any cause.
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FFBF, DM, CSM and OS were calculated from the time of commencement of RT until the event of interest occurred. Patients who had not experienced the event of interest at the time of data collection were considered right-censored. DM and CSM were presented as cumulative incidence curves while FFBF and OS were presented using the Kaplan-Meier method.
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A univariable and multivariable competing risk regression analysis using the method by Fine and Gray was performed for FFBF, where death from any cause was the competing event. The variables considered in this analysis were age at time of radiotherapy, pre-operative PSA and pre-radiotherapy PSA, and categorical variables including ISUP grade group, PSM, EPE, SVI and use of ADT. Sub-distribution hazard ratios with 95 percent confidence intervals and p-values were reported. Patients with missing data were excluded from the analysis. All statistical tests were 2-sided.
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The discriminative and predictive power of the Tendulkar [4] nomogram was assessed in the following way. The discriminative power was assessed by reporting the C-index whereas the predictive power was assessed by comparing the models predicted 5 and 10-year FFBF against the observed values.
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Baseline patient and treatment characteristics are listed in Table 1. 112 patients were treated between 2007-09 with SRT, with a median follow up of 10.0 years (interquartile range 9.3-10.7 years). The median year of RP was 2006 (IQR 2004-2007).
Table 1: Patient and treatment characteristics
Characteristic |
No. or median (IQR)
|
%
|
Median (IQR) age at surgery, years
|
61 (57-64)
|
|
Median (IQR) age at RT, years
|
63 (59-68)
|
|
Median (IQR) time from RP to RT, months
|
24 (14-46)
|
|
Median (IQR) pre-operative PSA, ng/mL
|
9 (6-12)
|
|
<10
|
72
|
64%
|
10-20
|
28
|
25%
|
>20
|
8
|
7%
|
Unavailable
|
4
|
4%
|
Grade group (Gleason score)
|
|
|
1 (≤6)
|
36
|
32%
|
2 (3+4)
|
48
|
43%
|
3 (4+3)
|
16
|
14%
|
4 (8)
|
8
|
7%
|
5 (9-10)
|
13
|
12%
|
Unknown
|
1
|
1%
|
High risk factors
|
|
|
Positive surgical margin
|
98
|
88%
|
Unknown
|
1
|
1%
|
Extraprostatic extension
|
57
|
51%
|
Unknown
|
1
|
1%
|
Seminal vesicle invasion
|
18
|
16%
|
Unknown
|
1
|
1%
|
Median (IQR) pre-RT PSA, ng/mL
|
0.4 (0.3-0.7)
|
|
0.01-0.2
|
19
|
17%
|
0.21-0.5
|
57
|
51%
|
0.51-1.0
|
12
|
11%
|
1.01-2.0
|
16
|
14%
|
>2.0
|
7
|
6%
|
Unknown
|
1
|
1%
|
Androgen deprivation therapy
|
16
|
14%
|
Abbreviations: IQR interquartile range, PSA prostate specific antigen, RP radical prostatectomy, RT radiotherapy