The impact

of

prostate volume on

genitourinary

toxicity

using a moderate

hypofractionation with volumetric modulated arc therapy for definitive prostate cancer

Aim: to analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer patients
treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc
therapy technique.
Matherials and methods: From January 2012 to March 2014, 104 patients with localized prostate cancer (PC) were
recruited in an internal protocol of moderate hypofractionation SIB schedule using VMAT technique (Varian
RapidArc, Palo Alto, California USA) for definitive treatment.
Clinical and dosimetric data were prospectively collected and retrospectively analyzed. For the intent of the current
analysis, 60 patients out of 104 were selected. The selection criteria were: a histologically confirmed
adenocarcinoma of the prostate, T1T3a, N0-1, M0, age <85 years, no recent (12 months) trans-urethral radical
prostatectomy (TURP), no urinary symptoms at baseline evaluation according to Common Terminology Criteria for
Adverse Events (CTCAE) v4.0 scoring system and an Eastern Cooperative Oncology Group (ECOG) performance
status 01. Patients were stratified into low (43%), intermediate (30%), and high-risk (27%) groups. Target volumes
(expanded to define the planning volumes (PTV)) were clinical target volume (CTV) 1: prostate; CTV2: CTV1 +
seminal vesicles; CTV3: CTV2 + pelvic nodes. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk 73.5
Gy to PTV1 and 60 Gy to PTV2; high-risk 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All treatments
were in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high risk
patients.
GU toxicities were scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system.
Results: The median follow-up was 24 months (range 10 - 36 months). GU acute toxicity was recorded as follow:
G0 = 16/60 (27%), G1 = 18/60 (30%); G2= 26/60 (43%); no case of toxicity G3 was registered. Rectal acute
toxicity was recorded as follow G0 = 24/60 (40%); G1 = 27/60 (45%); G2 = 9/60 (15%); no case of toxicity G3.
GU late toxicity was recorded as follow: G0 = 20/60 (34%); G1 = 29/60 (48%); G2 = 11/56 (19%); no case of
toxicity G3 was registered. Rectal late toxicity was recorded as follow: G0 = 39/60 (65%); G1 = 12/60 (20%); G2
= 9/60 (15%); no case of toxicity G3. The risk of acute G2 GU toxicity was about 3 times if the prostate volume is

 80 cc (p-value 0.004; 95% CI: 1.05 - 9.5). In the adjusted prediction model using the logistic regression, the
probability of acute G2 GU toxicity was about 60% with the same prostate volume cut-off (p-value 0.001; 95% CI:
0.13 - 0.46), with an attitude to develop a moderate toxicity in the first 3 weeks from the beginning of treatment. No
statistical correlation was found between a bladder planning volume inferior to 150-200-250 cc (p-value 0.15-0.810.75, respectively).
Regarding late toxicity, a trend to significance (p=0.076) to develop a GU toxicity G1 was found for V60 Gy
15%. A risk of developing a rectal toxicity different from G0 was estimated about 3 times greater if the rectal
volume is 60 cc (p-value 0.036; 95% CI: 1.07 - 9.5)
Conclusion: moderate hypofractionation with volumetric modulated arc therapy for definitive prostate cancer was
feasible and well tolerated. Acute and late toxicities were mild. Larger prostate volume could be predictor of
moderate acute GU toxicity and cautiously considered for intensification of symptomatic therapy.