University of Florida Proton Therapy Institute, Jacksonville, Florida 32206, USA.
Acta Oncol. 2013 Apr;52(3):463-9. doi: 10.3109/0284186X.2013.764467.
To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT.
Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78-82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively.
Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15-25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months.
Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15-25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15-25).
评估接受图像引导质子治疗（PT）的早期和中期前列腺癌患者的泌尿系统（GU）功能和毒性，并分析治疗前尿路梗阻症状对 PT 后泌尿系统功能的影响。
2006 年 8 月至 2007 年 9 月，我们进行了两项前瞻性试验，共入组 171 例前列腺癌患者。低危患者接受 78 钴格雷厄尔等效（CGE），分 39 次；中危患者接受 78-82 CGE。中位随访时间为 5 年。前瞻性记录国际前列腺症状评分（IPSS）和 GU 毒性（按 CTCAE v3.0 和 v4.0 分级）。
根据 CTCAE v4.0，有 5 例 GU 事件短暂达到 3 级，5 年时 GU 晚期毒性发生率为 2.9%。没有 4 级或 5 级事件。多因素分析（MVA）显示，唯一预测 2+GU 毒性的因素是治疗前 GU 症状管理（p=0.0058）。治疗前 IPSS 为 15-25 分的患者，治疗前 IPSS 中位数从 18 分下降到 60 个月时的 10 分，有临床改善。末次随访时，18 例（54.5%）患者 IPSS 下降>5 分，14 例（42.5%）患者稳定，2 例（3%）患者 IPSS 升高>5 分（恶化）。治疗前 IPSS<15 分的患者，治疗前和 60 个月时 IPSS 中位数稳定在 6 分。
采用图像引导 PT 治疗，5 年时泌尿系统毒性罕见且短暂。PT 治疗 5 年后，治疗前 IPSS<15 分的患者尿控功能稳定，但 15-25 分的患者 IPSS 中位数显著改善（下降），这一发现无法用α阻滞剂的起始或剂量调整来解释。这表明 PT 为低危和中危前列腺癌患者，包括有明显治疗前 GU 功能障碍（IPSS 15-25）的患者，提供了一种毒性小且有效的治疗方法。
