Hypothesis / aims of study
Radiation therapy (RT) is one of the treatment strategies for localized prostate cancer. Among the radiation therapies, carbon-ion radiotherapy (CIRT) has biological and physical advantages over RT using conventional X-rays. Carbon ion beams show an estimated three-fold higher relative biological efficacy than X-rays and have been reported good clinical outcomes for CIRT for localized prostate cancer [1]. On the other hand, radiation-induced urinary toxicities to the bladder and urethra can occur after CIRT, which adversely affect the patient's quality of life. However, there are no reports using objective assessments of urinary toxicities before and after CIRT. The purpose of this study is to clarify changes in lower urinary tract symptoms/dysfunctions before and after CIRT in patients with prostate cancer.
Study design, materials and methods
We obtained the consent of a prospective study on the assessment of lower urinary tract symptoms/dysfunctions before and after CIRT in patients scheduled to undergo CIRT for prostate cancer. The eligibility criteria for this study were: (i) histological diagnosis of prostate adenocarcinoma, (ii) cT1b-3bN0M0 according to the 7th UICC classification, and (iii) performance status 0–2. Of these, 46 patients had completed CIRT by the end of March 2022, and statistical analysis was performed on 27 patients, excluding 13 patients whose data was not collected and 6 patients who withdrew their consent. Patients were classified using the D'Amico risk group classification, with 11 patients in the intermediate-risk group and 16 patients in the high-risk group. All 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, with a total dose of 51.6 Gy(RBE). We evaluated lower urinary tract symptoms using the International Prostate Symptom Score (IPSS), Quality of Life (QOL) Score, and Overactive Bladder Symptom Score (OABSS). We also performed objective evaluations using frequency-volume charts (FVC), uroflowmetry (UFM), and post-void residual urine volume (PVR) measurement. These assessments were performed the following 3 times: before ADT, after 4-6 months of ADT (= just before CIRT), and immediately after CIRT. Of the 27 patients, four were taking α1 blockers, two were taking PDE5 inhibitors, and two were taking β3 adrenergic receptor agonists, before the start of ADT. One patient had a history of transurethral resection of the prostate. Statistical analysis was performed by paired t-test.
Results
The table shows the values of each parameter before ADT, before CIRT, and after CIRT. IPSS-2 (frequency),4 (urgency),5 (weak stream),7 (nocturia), IPSS-total score, and QOL score were significantly increased after CIRT compared to before ADT. OABSS-1 (daytime frequency) and OABSS-total scores were also significantly increased after CIRT. FVC showed no changes in 24-hour urine volume, the number of nocturnal voids, or the nocturnal polyuria index, but the number of daytime voids was significantly increased after CIRT. In UFM, maximum flow rate (Qmax), average flow rate (Qave), and voided volume (VV) were significantly decreased after CIRT compared to before ADT. There was no significant change in PVR.
Interpretation of results
This is the first report to investigate lower urinary tract symptoms/dysfunctions before and after CIRT using objective evaluations by FVC and UFM. Not only the patient's subjective complaints, but also objective evaluations showed an increase in the number of daytime voids, a decrease VV, and a decrease of the urinary stream. In a similar situation, there are few reports on the management of lower urinary tract symptoms after RT. One randomized study showed that tadalafil may be a good candidate for the management of lower urinary tract symptoms after low-dose-rate brachytherapy [2], however, there are no reports for that after CIRT. The limitations of this study are the small number of cases and the short observation period. The future task is to continue the evaluation for a long time after CIRT and accumulate the number of cases and clarify the treatment method for improving lower urinary tract symptoms/dysfunctions after CIRT.