Feasibility of Simultaneous Integrated Boost IMRT (SIB-IMRT) for Castration-Resistant Prostate Cancer

Discussion

The concept of CRPC includes a wide spectrum of conditions. We hypothesized that a curable patient group may exist after local radiation therapy in patients with CRPC without distant metastasis. Thus, we evaluated the efficacy and feasibility of local IMRT for the prostate with pelvic irradiation using the SIB technique to treat with curative intent CRPC patients after several lines of hormonal therapy.

In general, local IMRT is insufficient for treating patients with CRPC because microscopic lymph node metastasis potentially exists in the CRPC condition even though there is radiologically non-metastatic disease. Thus, we planned to irradiate pelvic lymph nodes simultaneously. Bolla et al. introduced external-beam radiation (EBRT) to pelvic lymph nodes in addition to local irradiation for locally advanced PCa (7). In their report, lymph node recurrence in the EBRT alone group was identified in 6 of 207 cases and was 0 of 208 in the hormone therapy combination group at a median of 65.7 months' follow-up in patients with locally advanced PCa (EORTC 22863 study). Their data suggest the usefulness of irradiating the pelvic lymph nodes with androgen ablation therapy only for cases with a high PSA and a high Gleason score.

Several authors have reported the toxicity of pelvic SIB-IMRT for patients with intermediate- to high-risk localized PCa (8, 9). The combination of SIB dose escalation and broad pelvic treatment with IMRT was generally well-tolerated in their series. However, no report has applied SIB-IMRT to treat CRPC. Several studies have reported an effect of EBRT on CRPC, but the results were limited (2, 3). Sasaki et al. concluded that EBRT for patients with localized CRPC is limited in terms of its effects on patient survival and has a role only in control of local symptoms (3). Akiyama et al. reported that EBRT for CRPC could achieve a 78% clinical relapse-free survival rate at 3 years (2). They treated patients with EBRT using the unblocked oblique four-field technique with a total dose of 69 Gy; however, some patients (19%) developed rectal bleeding due to radiation proctitis.

In the present study, 10 patients with CRPC were treated with SIB-IMRT after failure of several lines of hormone therapy. Although they were very high-risk cases, with a median follow-up of 33.5 months after SIB-IMRT, the biochemical relapse-free and overall survival rates at 5 years were 70% each and the median PSA nadir after SIB-IMRT was 0.02 ng/ml. In 2 of 10 cases, all hormone therapy was discontinued after SIB-IMRT due to undetectable PSA levels. These patients have been free from any hormone therapy for more than 1 year with no biochemical relapse. Another two cases stopped flutamide and estramustine, respectively, with no biochemical relapse, and the GnRH-agonist was continued by the physician's decision. It is thought that dose escalation and the extended irradiation field achieved by SIB-IMRT may have contributed to the curative effect.

As shown in Table III, the PSA nadir after initial hormonal therapy, the PSA value at initiation of SIB-IMRT, the PSA doubling-time before SIB-IMRT and the PSA nadir after SIB-IMRT were significantly related to biochemical progression after SIB-IMRT. It was interesting that a good response to initial hormonal treatment and earlier introduction of SIB-IMRT were related to disease control. However, there is no solid consensus on who becomes a good candidate for SIB-IMRT and when treatment should be started. Further prospective randomized trials will provide stronger confirmation.

All patients completed SIB-IMRT without treatment delay caused by acute toxicity. It was feasible to escalate the dose using the SIB technique and patients tolerated the treatment. It is thought that the SIB-IMRT technique greatly contributed to the reduction of RT-induced toxicity.

This study had several limitations. First, this was a retrospective study involving patients with various characteristics and treatments. Second, the sample size was very small and the observation period may not have been sufficient. In addition, a validated questionnaire for quality of life and morbidities was not provided. However, despite these limitations, the results provide valuable insight into CRPC treatment. Further studies are needed to clarify the role of SIB-IMRT for CRPC and randomized comparisons are required before definitive conclusions can be drawn.