Corn B W, Valicenti R K, Mulholland S G, Hyslop T, Gomella L
Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, USA.
Urology. 1998 May;51(5):782-7. doi: 10.1016/s0090-4295(98)00022-3.
At our institution, a Phase II trial using androgen suppression followed by surgery was completed for men with Stage T3 disease and negative laparoscopic nodal dissection. We recently reported the unfavorable biochemical outcome of that experience. Because that analysis did not include a control group of irradiated patients, the current project was undertaken to compare that Phase II experience with clinical Stage T3 patients treated at our institution with definitive irradiation during an overlapping period of time.
The Phase II trial included 21 patients with T3 tumors and negative laparoscopic nodal dissections treated by 4 months of neoadjuvant hormonal treatment (leuprolide +/- flutamide) prior to radical prostatectomy. Patients who declined to participate in the study or those judged ineligible by virtue of poor surgical risk were treated with definitive irradiation (n = 29). Although the radiation portals were shaped with multileaf collimation, no attempt was made to design "conformal fields." The median dose was 68 Gy (range 66 to 72) delivered in conventional fractionation. Biochemical failure after prostatectomy was defined as prostate-specific antigen (PSA) levels exceeding 0.2 ng/mL. Biochemical failure after irradiation was defined as a rise in absolute level of PSA greater than 1.5 ng/mL, or two consecutive elevations of PSA on sequential measurements, even if the absolute level was less than 1.5 ng/mL.
In univariate comparison, the freedom from biochemical relapse rate at 3 years was 41% for irradiated patients and 23% for those treated by hormones combined with surgery (P <0.05). In a multivariate regression model controlling for the prognostic factors of baseline PSA, age, clinical substage, Gleason score, and treatment modality (induction androgen suppression + prostatectomy versus radiotherapy), only low baseline PSA independently predicted improved freedom from biochemical recurrence (P = 0.04).
The combination of induction hormonal treatment followed by radical prostatectomy offered no advantage over irradiation alone in this single institutional experience. Notwithstanding, the majority of men treated by definitive radiotherapy manifested biochemical failure. More innovative strategies such as conformal irradiation (either alone or combined with androgen ablation) and radiation dose escalation should be pursued to optimize outcome for this unfavorable group of patients.
在我们机构，针对T3期疾病且腹腔镜淋巴结清扫阴性的男性患者，完成了一项先进行雄激素抑制然后手术的II期试验。我们最近报告了该试验令人不满意的生化结果。由于该分析未纳入接受放疗的对照组患者，因此开展了当前项目，以将该II期试验的结果与在我们机构同期接受根治性放疗的临床T3期患者进行比较。
II期试验纳入了21例T3肿瘤且腹腔镜淋巴结清扫阴性的患者，在根治性前列腺切除术前行4个月的新辅助激素治疗（亮丙瑞林±氟他胺）。拒绝参与研究或因手术风险高被判定不符合条件的患者接受根治性放疗（n = 29）。尽管放射野采用多叶准直塑形，但未尝试设计“适形野”。中位剂量为68 Gy（范围66至72），采用常规分割方式给予。前列腺切除术后生化失败定义为前列腺特异性抗原（PSA）水平超过0.2 ng/mL。放疗后生化失败定义为PSA绝对值升高大于1.5 ng/mL，或连续两次测量时PSA升高，即使绝对值小于1.5 ng/mL。
在单因素比较中，放疗患者3年无生化复发率为41%，激素联合手术治疗患者为23%（P <0.05）。在控制基线PSA、年龄、临床分期、Gleason评分和治疗方式（诱导雄激素抑制+前列腺切除术与放疗）等预后因素的多因素回归模型中，只有低基线PSA独立预测生化复发无进展改善（P = 0.04）。
在这一单一机构经验中，诱导激素治疗后行根治性前列腺切除术与单纯放疗相比并无优势。尽管如此，大多数接受根治性放疗的男性出现了生化失败。应采用更具创新性的策略，如适形放疗（单独或与雄激素消融联合）和增加放射剂量，以优化这一预后不良患者群体的治疗效果。
