The issues regarding postoperative adjuvant therapy and prognostic risk factors for patients with stage I–II cervical cancer: A review

Abstract

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.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis

“…In the current study, 90.3% of patients completed the treatment protocol as planned and grade 3‐4 gastrointestinal toxicities occurred in only 1 patient. There has recently been much debate regarding the risk‐benefit balance of postoperative CCRT for cervical cancer . Postoperative CCRT would be expected to induce serious gastrointestinal toxicity, which could continue throughout the patient's life; this is because the organ in the pelvis that would be targeted by RT has already been subjected to radical surgery .…”

“…There has recently been much debate regarding the risk‐benefit balance of postoperative CCRT for cervical cancer . Postoperative CCRT would be expected to induce serious gastrointestinal toxicity, which could continue throughout the patient's life; this is because the organ in the pelvis that would be targeted by RT has already been subjected to radical surgery . Takekuma et al report that the level of invasiveness of the surgical procedure might be associated with the toxicities of adjuvant CCRT, which meant that patients with ≥40 dissected lymph nodes had significantly more non‐hematological toxicities of adjuvant CCRT than those with <40.…”

“…Patients with LNM have been shown to exhibit a greater rate of distant failure than those without this, so postoperative adjuvant therapy should not only control local recurrence, but also prevent distant metastasis. Postoperative CCRT would be expected to induce serious toxicities, which could continue throughout the patient's life; this is because the organ in the pelvis targeted by RT has already been subjected to radical surgery . In this context, systemic chemotherapy (CT) alone could play an important role as postoperative adjuvant therapy for patients with high‐risk cervical cancer.…”

“…[4][5][6][7][8] There has recently been much debate regarding the risk-benefit balance of postoperative CCRT for cervical cancer. [9][10][11][12] Patients with LNM have been shown to exhibit a greater rate of distant failure than those without this, 9,10 so postoperative adjuvant therapy should not only control local recurrence, but also prevent distant metastasis.…”

“…Postoperative CCRT would be expected to induce serious toxicities, which could continue throughout the patient's life; this is because the organ in the pelvis targeted by RT has already been subjected to radical surgery. 11,12 In this context, systemic chemotherapy (CT) alone could play an important role as postoperative adjuvant therapy for patients with high-risk cervical cancer.…”