Hypothesis / aims of study
Radiation therapy (RT) is one of the treatment strategies for localized prostate cancer. Among RTs, carbon-ion radiotherapy (CIRT) is biologically superior to conventional X-ray-based RT, and favorable clinical outcomes of CIRT for localized prostate cancer have been reported [1]. On the other hand, radiation-induced lower urinary tract complications to the bladder and urethra may occur after CIRT, adversely affecting the quality of life of patients. However, there are no reports using objective assessment of chronological changes in lower urinary tract complications after CIRT. The purpose of this study is to clarify the chronological changes in lower urinary tract symptoms and dysfunctions after CIRT for prostate cancer patients.
Study design, materials and methods
A prospective study for patients scheduled to undergo CIRT for prostate cancer was conducted to assess lower urinary tract symptoms/dysfunctions pre- and post-CIRT. Eligibility criteria for the study were: (i) histological diagnosis of prostate adenocarcinoma, (ii) cT1b-3bN0M0 according to the 7th UICC classification, and (iii) performance status 0-2. We obtained consent from 221 patients and performed statistical analysis in 169 of these patients who did not drop out of the study until the first year after completion of CIRT. Patients were classified using the D'Amico risk group classification, with 3 patients in the low-risk group, 62 in the intermediate-risk group, and 104 in the high-risk group. All intermediate- and high-risk patients received neoadjuvant androgen deprivation therapy (ADT) for 4-6 months prior to CIRT; CIRT was performed once a day, 4 days a week for 3 weeks, for a total dose of 51.6 Gy (RBE). Lower urinary tract symptoms were assessed using the International Prostate Symptom Score (IPSS), Quality of Life Score (QOL score), and Overactive Bladder Symptom Score (OABSS). Objective assessments were also made using the Frequency Volume Chart (FVC), uroflowmetry (UFM), and post-void residual volume (PVR) measurements. These assessments were performed at the following six times: before ADT (i.e., baseline), 4-6 months after ADT (i.e., pre-CIRT), after a series of CIRT was completed (post-CIRT), and 3, 6, and 12 months after CIRT. Paired t-tests were used to compare individual data between baseline and each assessment time point, and the Bonferroni method was used to adjust for multiple comparisons. Significant differences were assessed using two-sided tests with P < 0.001.
Results
The table shows the values of each parameter baseline, pre-CIRT, post-CIRT, and at 3, 6, and 12 months after CIRT. The IPSS, QOL score, and OABSS parameters were significantly worse for almost all sub-scores at post-CIRT compared to baseline, but they were tended to recover 3 to 6 months after CIRT. In FVC, there were no significant changes in 24-hour urine volume or nocturnal polyuria index, but nocturnal voiding frequency was prolonged until 12 months after CIRT. In UFM, maximal flow rate (Qmax) and average flow rate (Qave) significantly worsened post-CIRT, but tended to recover 3 to 6 months after CIRT. The decrease in single voided volume persisted until 12 months after CIRT. There were no significant changes in PVR, and no patients required indwelling urethral catheters or intermittent catheterization.
Interpretation of results
This is the first report to investigate lower urinary tract symptoms and dysfunctions pre- and post-CIRT with objective findings by FVC and UFM over 1 year period. In addition to the patient's subjective complaints, objective evaluation also showed an increase in the number of nocturnal micturition and a decrease in the volume per micturition.
There are few reports on the management of lower urinary tract symptoms after radiotherapy in similar settings. In a paper, lower urinary tract symptoms, including storage symptoms, was worst at 3 months after brachytherapy but improved chronologically [2]. In our study, the worsening of symptoms peaked immediately after CIRT, and at 3 months after CIRT, there was a tendency for improvement in all parameters except for voided volume on UFM. The faster recovery of lower urinary tract symptoms with CIRT compared with brachytherapy, may be due to the difference in radiation dose and the lesser effect of irradiation on the bladder.
Radiation therapy has the potential for late urinary toxicity, and long-term follow-up is desirable in this type of study. Additionally, this study only included patients who received CIRT and was not a randomized controlled trial. However, knowing the chronological changes in lower urinary tract symptoms on CIRT may help patients make better-informed decisions for treatment.