Takekuma Munetaka, Kasamatsu Yuka, Kado Nobuhiro, Kuji Shiho, Tanaka Aki, Takahashi Nobutaka, Abe Masakazu, Hirashima Yasuyuki
Shizuoka Cancer Center, Suntogun, Japan.
J Obstet Gynaecol Res. 2017 Apr;43(4):617-626. doi: 10.1111/jog.13282. Epub 2017 Feb 11.
The treatment for most patients with early-stage cervical cancer involves radical hysterectomy and pelvic lymph node dissection, and indications for postoperative adjuvant therapy have been determined by evaluating the prognostic risk factors for recurrence in each case. The aim of this review is to raise and discuss the various issues that have not yet been resolved regarding the prognostic risk factors and postoperative adjuvant therapy. Several clinicopathological factors, such as tumor size, lymphovascular space involvement, deep stromal invasion, parametrial involvement and lymph node metastasis, have been identified to have prognostic significance in early-stage cervical cancer. However, this remains controversial because there is suggested to be substantial heterogeneity among patients after radical hysterectomy and lymphadenectomy and it would be difficult to define the risk groups clearly. This indicates the need to develop more convenient and accurate criteria to define risk groups. According to the currently available evidence, patients in the high-risk group should receive adjuvant concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) and fluolouracil. However, CCRT with CDDP administered weekly (CCRT-P) has instead been applied in a clinical context worldwide. Whether CCRT-P has a survival benefit compared with radiotherapy (RT) alone is unknown because no randomized phase III trials have been performed for patients in the high-risk group after radical surgery. Patients with high-risk factors have a high incidence of distant metastasis, for whom systemic chemotherapy might be a key to improving overall survival. The pivotal study that investigated the role of RT alone for patients with intermediate-risk factors after hysterectomy is the GOG092 trial. This trial showed a 47% reduction in the risk of recurrence after RT compared with no further treatment (NFT). However, the improvement in overall survival with RT did not reach statistical significance, while patients allocated to the RT group did experience an increase in severe toxicities compared with the NFT group. This could be why many physicians are reluctant to treat patients with this approach, although guidelines recommend RT for patients with intermediate-risk factors. With regard to toxicities, postoperative RT would be problematic because the organs in the pelvis targeted by RT have already been damaged by radical surgery. To reduce the toxicities, intensity-modulated radiotherapy would best be used worldwide. Further improvement in adjuvant therapy will come from enhanced definition of prognostic risk factors, better patient selection, and refinements in both local and systematic therapies.
大多数早期宫颈癌患者的治疗包括根治性子宫切除术和盆腔淋巴结清扫术，术后辅助治疗的指征是通过评估每个病例复发的预后危险因素来确定的。本综述的目的是提出并讨论关于预后危险因素和术后辅助治疗尚未解决的各种问题。一些临床病理因素，如肿瘤大小、脉管间隙浸润、深部间质浸润、宫旁组织受累和淋巴结转移，已被确定在早期宫颈癌中具有预后意义。然而，这仍然存在争议，因为根治性子宫切除术和淋巴结切除术后患者之间存在明显的异质性，难以清晰地界定风险组。这表明需要制定更方便、准确的标准来界定风险组。根据目前可得的证据，高危组患者应接受顺铂（CDDP）和氟尿嘧啶的辅助同步放化疗（CCRT）。然而，每周应用顺铂的CCRT（CCRT-P）已在全球临床中应用。与单纯放疗（RT）相比，CCRT-P是否具有生存获益尚不清楚，因为尚未对根治性手术后的高危组患者进行随机III期试验。具有高危因素的患者远处转移发生率高，对于他们而言，全身化疗可能是提高总生存率的关键。研究子宫切除术后中度危险因素患者单纯放疗作用的关键研究是GOG092试验。该试验显示，与未进一步治疗（NFT）相比，放疗后复发风险降低了47%。然而，放疗对总生存率的改善未达到统计学意义，而与NFT组相比，分配到放疗组的患者严重毒性反应有所增加。这可能就是尽管指南推荐对中度危险因素患者进行放疗，但许多医生仍不愿采用这种方法治疗患者的原因。关于毒性反应，术后放疗会有问题，因为放疗所针对的盆腔器官已因根治性手术而受损。为降低毒性反应，全球最好采用调强放疗。辅助治疗的进一步改善将来自于对预后危险因素的更精确界定、更好的患者选择以及局部和全身治疗的优化。
