Ryckman Jeffrey M, Thomas Toms V, Wang Ming, Wu Xue, Siva Shankar, Spratt Daniel E, Slotman Ben, Pal Sumanta, Chapin Brian F, Fitzal Florian, Soran Atilla, Bex Axel, Louie Alexander V, Lehrer Eric J, Zaorsky Nicholas G
Department of Radiation Oncology, West Virginia University Medicine Camden Clark Medical Center, Parkersburg, West Virginia.
Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi.
Int J Radiat Oncol Biol Phys. 2022 Dec 1;114(5):919-935. doi: 10.1016/j.ijrobp.2022.06.095. Epub 2022 Jul 15.
Local treatment of the primary tumor for patients with metastases is controversial, and prospective data across many disease sites have conflicting conclusions regarding benefits.
A comprehensive search was conducted in PubMed/MEDLINE including randomized controlled trials (RCTs) published in the past 50 years. Inclusion criteria were multi-institutional RCTs of patients with metastatic disease receiving systemic therapy randomized to addition of local treatment to the primary tumor. Two primary outcome measures, overall survival (OS) and progression-free survival (PFS), were quantitatively assessed using random effects, and meta-analyses were conducted using the inverse variance method for pooling. Secondary endpoints were qualitatively assessed and included toxicity and patient-reported quality of life. Exploratory analyses were performed by treatment type and volume of disease.
Eleven studies comprising 4952 patients were included (1558 patients received radiation therapy and 913 patients received surgery as primary tumor treatment). OS and PFS were not significantly improved from treatment of the primary (OS: hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.80-1.05; PFS: HR, 0.88; 95% CI, 0.72-1.07). Assessment of primary local treatment modality demonstrated a significant difference in summary effect size on PFS between trials using surgery (HR, 1.15; 95% CI, 0.99-1.33) compared with radiation therapy (HR, 0.73; 95% CI, 0.56-0.96) as the local treatment modality (P = .005). In low metastatic burden patients, radiation therapy was associated with significantly improved OS (HR, 0.67; 95% CI, 0.52-0.85), but surgery was not associated with improved OS compared with no local treatment (HR, 1.12; 95% CI, 0.94-1.34).
In RCTs conducted to date enrolling a variety of cancer types with variable metastatic burden, there is no consistent improvement in PFS or OS from the addition of local therapy to the primary tumor in unselected patients with metastatic disease. Carefully selected patients may derive oncologic benefit and should be discussed in tumor boards. Future prospective studies should aim to further optimize patient selection and the optimal systemic and local therapy treatment types.
对于有转移灶的患者，对原发肿瘤进行局部治疗存在争议，并且来自多个疾病部位的前瞻性数据在获益方面存在相互矛盾的结论。
在PubMed/MEDLINE中进行了全面检索，包括过去50年发表的随机对照试验（RCT）。纳入标准为针对接受全身治疗的转移性疾病患者的多机构RCT，这些患者被随机分配接受原发肿瘤的局部治疗。使用随机效应定量评估两个主要结局指标，即总生存期（OS）和无进展生存期（PFS），并使用逆方差法进行荟萃分析以汇总数据。对次要终点进行定性评估，包括毒性和患者报告的生活质量。按治疗类型和疾病范围进行探索性分析。
纳入了11项研究，共4952例患者（1558例患者接受放射治疗，913例患者接受手术作为原发肿瘤治疗）。对原发肿瘤的治疗并未显著改善OS和PFS（OS：风险比[HR]，0.91；95%置信区间[CI]，0.80 - 1.05；PFS：HR，0.88；95%CI，0.72 - 1.07）。对原发局部治疗方式的评估表明，与使用放射治疗（HR，0.73；95%CI，0.56 - 0.96）作为局部治疗方式的试验相比，使用手术作为局部治疗方式的试验在PFS的汇总效应大小上存在显著差异（P = 0.005）。在低转移负担患者中，放射治疗与显著改善的OS相关（HR，0.67；95%CI，0.52 - 0.85），但与未进行局部治疗相比，手术并未改善OS（HR，1.12；95%CI，0.94 - 1.34）。
在迄今为止纳入多种癌症类型且转移负担各异的RCT中，对于未选择的转移性疾病患者，在原发肿瘤上加用局部治疗并未使PFS或OS得到一致改善。仔细选择的患者可能会获得肿瘤学益处，应在肿瘤病例讨论会上进行讨论。未来的前瞻性研究应旨在进一步优化患者选择以及最佳的全身和局部治疗类型。
