We investigated the preliminary results of CIRT using the spot scanning method for prostate cancer in the present study. To the best of our knowledge, this is the first report about the clinical outcomes of prostate cancer patients after undergoing CIRT with the spot scanning method.
Late GI toxicity is often a problem with RT for prostate cancer. Technological improvements in RT, such as IMRT and particle therapy, can provide a better dose distribution to the target and spare the normal surrounding tissues. In patients with prostate cancer treated with high-dose 3DCRT, grade 2 or greater late GI toxicity was observed 14–24% of patients in a prior study [25–28]. Meanwhile, the rate of grade 2 or greater late GI toxicity was reduced to 5–15% using IMRT to spare the rectal dose [29–31].
Moreover, particle therapy can more strongly reduce the rectal dose than IMRT based on its sharp dose distribution to the target. According to results of a phase II clinical trial analyzing 84 patients treated with proton beam RT, the incidence of grade 2 late GI toxicity was 13% . Iwata et al. reported the results of a multi-institutional retrospective survey of proton therapy for prostate cancer in Japan, and the incidence rate of grade 2 or greater severe late GI toxicity was 4.6% .
Late GI toxicity is also known as dose-limiting factor in CIRT for prostate cancer. In a dose escalation study of CIRT for prostate cancer, grade 3 late GI toxicity developed in 36% of patients who received a dose of 72 Gy . However, according to a phase II clinical study of CIRT for prostate cancer using a total dose of 66 Gy delivered in 20 fractions, grade 2 GI toxicity was observed in 2% of the patients . Additionally, in a multi-institutional study of CIRT for prostate cancer, the incidence of grade 2 rectal toxicity was only 0.8% . Similar results were obtained in the present study. In the study of the correlation between late GI toxicity and CIRT, anticoagulation therapy was associated with a 2.7-fold risk of late GI toxicity . In the present study, significant correlation was not observed between anticoagulation therapy and late GI toxicity.
In this study, TURP was significantly associated with grade 2 late GU toxicity. In a study of IMRT demonstrated that previous TURP was associated with late GU toxicity . Other study of IMRT, DM was reported as a predictive factor for late Grade 2 or greater GU toxicities . In the present study, DM was tended to correlate with Grade 2 late GU toxicity. In terms of late GU toxicity after CIRT, it was reported that longer ADT duration was a predictor of late GU toxicity . A significant correlation between ADT duration and late GU toxicity was not observed in the present study. Few studies have assessed the correlation between ADT duration and late GU toxicity, therefore, further studies are required to assess the relationship between CIRT and GU toxicity.
Several studies have demonstrated dose response in prostate cancer [4–7]. Only ADT is not sufficient for the definitive treatment for prostate cancer; high-dose radiation therapy is required . According to these features of prostate cancer and because of the biological and physical advantages in CIRT, it is considered that CIRT is appropriate for the management of prostate cancer. In fact, favorable BFS rates have been reported in patients treated with CIRT. Ishikawa et al. reported a 5 year BFS rate of 90.6% for patients with prostate cancer treated with CIRT at a total dose of 66 Gy (RBE) delivered in 20 fractions . In a multi-institutional analysis of CIRT, the 5 year BFS rates in the low-, intermediate-, and high-risk groups were 92%, 89%, and 92%, respectively . In the present study, the BFS rate was worst in the low-risk group and best in the high-risk group. The two major reasons to explain these results are as follows. First, the number of the low-risk patients was small, i.e., only eight patients. Therefore, the BFS rate in the low-risk group seemed to be relatively higher than that in the other group; furthermore, there was only one case of biochemical relapse. One of these eight low-risk patients experienced PSA elevation immediately after CIRT, which may have been a benign temporary PSA elevation called PSA bounce; however, its significance was unclear owing to immediate ADT after PSA elevation without any radiological confirmation of clinical recurrence. Second, high-risk patients received ADT for a longer duration. In the present study, the high-risk group underwent ADT for a total of 2 years; thus, high-risk patients received ADT at least 1 year after the completion of CIRT. Therefore, the observation period was not sufficient to estimate the BFS rate in our study, and further observation will be necessary to confirm our treatment outcome.
In the present study, biochemical failure was observed in 14 patients, with PSA levels decreasing without treatment in 11 patients. PSA fluctuations without any clinical signs of cancer recurrence after RT follow-up are known as PSA bounces, and they are often observed after brachytherapy and/or external beam RT . PSA bounces after low-dose brachytherapy occurs in 28–49% of patients using a 0.2 ng/ml definition [39–41]. In approximately 10% of patients, the PSA bounce exceeds the 2 ng/ml limit . Age was one of the first and most frequently described predictive factors of the PSA bounce [39, 40]. A similar tendency was observed in the present study. There has been no study of PSA fluctuations after CIRT. The clinical significance of PSA fluctuations is unclear, and further study is required.
The present study had several limitations such as its single-institutional nature and short observation period. More than 80% of late toxicities occurred within 2 years after CIRT ; therefore, toxicities were evaluated for a sufficient period in the present study. Further observation with a large patient cohort will be necessary to confirm our clinical outcome.