积极监测对低风险前列腺癌患者更有利

《临床癌症研究》9月24日在线发表的一项研究报告显示，与立即接受根治性前列腺切除术相比，行积极监测的低风险前列腺癌男性患者癌症特异性生存期减少“甚微”，仅1.8个月。然而，后者可少受6年多的治疗以及由此导致的不良反应痛苦(Clin. Cancer Res. 2012 Sept. 24 [doi:10.1158/1078-0432.CCR-12-1502])。

Fred Hutchinson癌症研究中心的Ruth Etzioni博士及其同事利用现有研究数据，通过其开发的新模型预测了100万虚拟美国同期前列腺癌患者的死亡率。


Ruth Etzioni博士

首先，研究者对一项积极监测项目数据进行模拟模型分析。纳入该项目的低风险癌症患者每年接受活检，如果发现患者出现不良变化则进一步治疗。此外，如果患者前列腺特异抗原(PSA)水平升高或对“观察等待”不放心，可自行要求进一步治疗。然后，对CaPSURE研究资料进行模型分析。该项大规模纵向研究纳入了40家泌尿外科收治的14,000例患者，考察了患者从接受根治性前列腺切除术至复发的时间，资料包括了1,000项临床和患者变量。研究者还利用另一项纳入3,470例患者的队列研究数据，对患者从前列腺癌复发至死亡时间进行模型分析。最终，计算接受积极监测和立即根治性前列腺切除术模拟队列的累计癌症特异性死亡率。

结果显示，该模型预测接受积极监测和立即根治性前列腺切除术患者20年累计前列腺癌特异性死亡率将分别为2.78%和1.64%，相当于立即行根治性前列腺切除术患者生存期平均延长1.8个月，优势“甚微”。然而，该模型还显示，接受积极监测的患者能多享受6.4年没有治疗及其副作用的生活，优势非常明显。

3项独立的敏感性分析表明，即使有多种变量发生变化，该模型仍具有强大的预测性能。所有敏感性分析所得出的积极监测患者累计前列腺癌特异性死亡率差异很小，这也支持了积极监测对低风险癌症患者生命预期影响很小的预测结果。

此外，该模型还预测大约64%的主动监测患者最终将接受治疗，即意味着36%的积极监测患者将免于治疗。

上述结果至少与另外一项模型研究结果和纵向PIVOT研究结果相一致，后者随访了患者无病生存期时间达12年。研究者指出，虽然上述结果并非最新发现，但证实了研究者的预期结果，也确认了既往有关观察等待的研究结果：极少数低风险前列腺患者死于观察等待，观察等待与接受治疗差异似乎非常小。

该研究由美国国立癌症研究所和疾病控制预防中心资助。研究者无利益冲突披露。

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By: MARY ANN MOON, Internal Medicine News Digital Network

Compared with immediate radical prostatectomy, active surveillance for men with low-risk prostate cancer produces only a "very modest" 1.8-month decrease in cancer-specific survival, according to a report published online Sept. 24 in Clinical Cancer Research.

However, men on active surveillance enjoyed 6 more years of life free from treatment and its adverse effects than men who had immediate surgery, said Dr. Ruth Etzioni of the division of public health services, Fred Hutchinson Cancer Research Center, Seattle, and her associates.

These are the findings of a new simulation model they developed to predict prostate cancer mortality in a virtual population of 1 million contemporary U.S. cases, using the best available data from contemporary studies of the issue.

The investigators first incorporated into their simulation model the findings from an active surveillance program in which men with low-risk prostate cancer are biopsied every year and referred for further treatment if any adverse changes are found. This program also allows patients to self-refer for further treatment for several other reasons, including if their prostate-specific antigen level rises or if they become too anxious over "watchful waiting."

The researchers then incorporated into the model information from a large longitudinal database on the interval between radical prostatectomy and recurrence. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database enrolled nearly 14,000 men treated at 40 urology practices, and included 1,000 clinical and patient variables.

Lastly, Dr. Etzioni and her colleagues used data from another cohort study of 3,470 men to model the time from prostate cancer recurrence until death. They then computed the cumulative cancer-specific mortality in their virtual cohort for men under active surveillance compared with men who underwent immediate radical prostatectomy.

The model projected that the 20-year cumulative rate of prostate cancer–specific mortality would be 2.78% with active surveillance and 1.64% with immediate radical prostatectomy. This corresponded with an average of 1.8 months of life saved per case, which was considered a "very modest" advantage, the investigators said (Clin. Cancer Res. 2012 Sept. 24 [doi:10.1158/1078-0432.CCR-12-1502]).

However, the model also showed that men on active surveillance "had on average 6.4 more years of life free from treatment and its side effects," which could be a substantial advantage.

Three separate sensitivity analyses demonstrated that the model’s projections were robust even when multiple variables were altered. "All sensitivity analyses produced only modest differences in cumulative prostate cancer mortality under active surveillance, and supported our projection that active surveillance would have a minimal impact on life expectancy for low-risk cancer cases," Dr. Etzioni and her associates said.

"Ultimately, the model predicts that approximately 64% of men on active surveillance would be treated [for prostate cancer] within their lifetimes. ... Thus, under active surveillance, 36% of men could avoid being treated," they said.

These findings are consistent with those of at least one other modeling study and with those of the longitudinal PIVOT (Prostate Cancer Intervention versus Observation Trial) study that tracked disease-free survival for 12 years.

"Although this is not a new result, it is confirmation of what we expected, and it substantiates data from previous studies looking at watchful waiting. Very few men with low-risk disease die from prostate cancer regardless, and the difference between treatments appears to be very modest," Dr. Etzioni said in a press statement accompanying this report.

This study was supported by the National Cancer Institute and the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.