In the management of cT4 PC, the addition of local therapy to systemic therapy was associated with improved survival when compared to systemic therapy alone [3], but the optimal local therapy has not yet been established. We have treated locally advanced PC invading the bladder with CIRT with long-term ADT, expecting that the physical and biological advantages of CIRT over photon RT would yield therapeutic benefits. Thus, we evaluated the safety and efficacy of the CIRT in the current study. To the best of our knowledge, this is the first report describing CIRT with long-term ADT for locally advanced PC with bladder invasion. Our findings showed that none of the 7 patients had severe toxicity, and 6 (85.7%) patients had no recurrence or metastasis with the median follow-up period of 78 months.
There are limited literatures on the surgery for cT4 PC. Hajili et al. showed that the prostate cancer-specific survival (PCSS) rates for cT4 PC at 150 months after inductive ADT and subsequent RP were 82%, and 10.3% of the patients had complications requiring surgical intervention [12]. Kumazawa et al. reported cystoprostatectomy followed by immediate hormone therapy for cT4N0M0 disease. In their study, the PCSS rate at 5 years after the surgery was 87.1% [13]. These findings showed relatively favorable survival despite the advanced disease, although it should be noted that these surgical indications were limited to patients with good general conditions.
EBRT, which is a less invasive treatment modality compared to surgery, is also recommended for very high risk PC including cT4 disease [1]. Furthermore, intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy enable higher dose to tumors with lower dose to organs at risk, resulting in the lower incidence of AE and improved biochemical relapse free survival (bRFS) [14]. In addition, EBRT with high-dose-rate brachytherapy boost may improve bRFS [15]. To our knowledge, little is known regarding the outcomes of patients with cT4 PC treated with EBRT, although a clinical trial to analyze whether surgical treatment or EBRT using photons is the better treatment for cT4 PC is undergoing [16].
CIRT, a kind of EBRT, contributes to favorable outcomes especially in advanced PC. Kasuya et al. reported that the prostate cancer specific mortality at 5 years after CIRT with long-term ADT was 1.5% for high risk PC [17]. We previously reported that the 5-year biochemical relapse-free rate of high risk PC was 92.0% in a single-institutional prospective study [8]. The present study showed that 85.7% (6/7) of the patients had no biochemical failure and all the patients were alive at the median follow-up period of 78 months. We cannot compare these results with those of EBRT due to the lack of available literature specific to cT4 PC, but when compared with the surgical treatment options, our results seem to be favorable, although we acknowledge that the number of patients included in our study is extremely small.
In general, CIRT is also remarkable for the low incidence of late toxicity because of the superior dose accumulation. We previously demonstrated that 9% of the patients had grade 2 late toxicities after CIRT [8], while Cahlon et al. showed that up to 23% of the patients had grade 2 late toxicities after photonbased IMRT [18]. In CIRT for PC with bladder invasion, the irradiated volume of the bladder was larger than that in PC without bladder invasion, which potentially increases the incidence and severity of urinary toxicity. However, with the careful management of inter-fractional displacements mentioned above, there was only 1 patient with grade 2 late urinary disorder in the current study, thus supporting that CIRT is tolerable for patients with locally advanced PC with bladder invasion.
These favorable outcomes of the present study may be due to the physical and biological advantages of CIRT over photon RT, which may have provided therapeutic benefits for locally advanced PC. Although our findings provide only the weakest evidence, we are encouraged to further explore the safety and efficacy of CIRT for PC with bladder invasion in larger cohorts.
The present study has some limitations. As mentioned above, this is a case series report with extremely small number of patients; thus, some potential sources of bias were not excluded. In addition, the effects of clinical and pathological factors such as age, initial PSA level, Gleason score, the number of positive cores in biopsy samples, and the duration of ADT were not argued in this study. Larger cohort is needed to evaluate these factors.