术后放疗可减缓前列腺癌进展

10月19日《柳叶刀》在线报告的一项随机Ⅲ期试验长期随访数据表明，与等待观察方案相比，术后立即放疗可减少根治性前列腺癌切除术患者前列腺癌生化进展，但对总生存率未见影响，并且对于70岁以上患者还可能具有不利影响(doi: 10.1016/S0140-6736(12)61253-7)。

法国米萨隆大学中心医院的Michel Bolla博士及其同事考察了入组欧洲癌症研究与治疗组织(EORTC)22911试验的1,005例男性患者，患者中位年龄65岁，中位随访时间为10.6年。队列中包括前列腺癌未治患者和至少有以下情况的患者：包膜穿孔、切缘阳性或精囊浸润。所有患者均接受根治性前列腺癌切除术，术后被随机分组，分别接受术后即时体外放疗(术后16周内)或等待观察，后者出现生化或临床复发后再接受后续治疗。

总体上，术后放疗组有198例(39.4%)患者出现生化进展(定义为间隔至少2周的2次检测前列腺特异性抗原水平增加>0.2 mcg/L)、临床进展或死亡，而等待观察组有311例(61.8%)患者出现进展或死亡，放疗方案风险比(HR)为0.49(P<0.0001)。

按年龄分层后的结果显示，与等待观察组相比，放疗组<70岁患者无生化进展生存率(HR，0.44；P<0.0001)和无临床进展生存率(HR，0.67；P=0.0013)均有所改善。但放疗组≥70岁患者死亡率大于等待观察组，死亡比例分别为40例/94例和20例/102例(HR，2.94；P<0.0001)。总体上，放疗组和等待观察组10年全因生存率未见显著差异，分别为76.9%和80.7%；前列腺癌死亡率也未见组间差异。

该研究由法国国家癌症防治联盟和EORTC慈善信托基金资助，研究者报告无相关利益冲突。

随刊述评：选择患者是关键

麻省总医院放射肿瘤科的Jason A. Efstathiou博士指出，制定前列腺癌治疗决策需要汇集泌尿肿瘤团队中内、外和放射科专家的意见。手术治疗有可能以治愈为目的，但前瞻性数据仍支持术后放疗。泌尿肿瘤团队有义务与患者讨论术后放疗方案，如果可行，还应确定最佳治疗时机，如果不行也应说明理由。展望未来，正在广泛开发应用的新影像模式，诸如淋巴细胞纳米颗粒及多参数MRI和PET(18F-氟化钠、18F-乙酸、11C-乙酸、18F-胆碱等)为前列腺癌治疗带来了新的希望，这方面的进展将有助于确认究竟哪些患者最有可能受益于术后放疗。

Efstathiou博士声称无相关利益冲突。

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By: DENISE NAPOLI, Oncology Practice

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

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Selection of Patients Is Key

In a comment accompanying the article, Dr. Jason A. Efstathiou wrote that "the decision to treat [prostate cancer] needs multidisciplinary input" from the entire uro-oncology team, including surgical, radiation, and medical specialists (Lancet 2012 Oct. 19 [doi: 10.1016/S0140-6736(12)61253-7]).

"When surgery has probably not cured a patient, prospective data still support postoperative radiation. The onus is on the uro-oncology team (surgical, radiation, and medical) to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and provide justification when it is not," he wrote.

Looking to the future, "novel imaging modalities, such as lymphotropic nanoparticle and multiparametric MRI and PET (18F-sodium fluoride, 18F-acetate, 11C-acetate, 18F-choline, 11C-choline, and others), are being explored extensively, and provide further promise," he added.

"Such advances might help discern which patients are most likely to benefit from postoperative radiation."

DR. EFSTATHIOU is with the department of radiation oncology at Massachusetts General Hospital in Boston. He declared that he had no conflicts of interest.