Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis

Sala, Paolo; Bogliolo, Stefano; Barra, Fabio; Fazio, Alessandra; Maramai, Mattia; Cassani, Chiara; Gardella, Barbara; Babilonti, L; Giannelli, Flavio; Mammoliti, Serafina; Spinillo, Arsenio; Ferrero, Simone; Menada, Mario Valenzano; Costantini, Sergio; Bruzzi, Paolo; Marchiolè, Pierangelo

doi:10.1080/08941939.2020.1856239

Cited by 11 publications

(11 citation statements)

References 21 publications

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“…Later retrospective studies comparing neoadjuvant chemotherapy followed by surgery with concurrent chemotherapy have also reported improved outcomes in terms of disease-free and overall survivals, and suggested the use of this approach, especially in young pre-menopausal women desiring sexual function 26 27. However, most of these studies have selection bias due to their retrospective or non-randomized design and could not establish neoadjuvant chemotherapy as the standard of care for any sub-set of patients with cervical cancer.…”

Section: Rationale For Neoadjuvant Chemotherapy Followed By Surgerymentioning

confidence: 99%

Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future

Miriyala

Mahantshetty

Maheshwari

et al. 2022

Int J Gynecol Cancer

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BackgroundCisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer.MethodsA comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer.ResultsRandomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25–30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy.ConclusionNeoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.

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Section: Rationale For Neoadjuvant Chemotherapy Followed By Surgerymentioning

confidence: 99%

Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future

Miriyala

Mahantshetty

Maheshwari

et al. 2022

Int J Gynecol Cancer

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“…NAC is a useful treatment option for patients with cervical cancer; therefore, a significant amount of research has focused on the use of NAC for patients with cervical cancer in recent years. For instance, Sala et al (8) reported that NAC improved the survival outcome for patients with stage IB2-IVA uterine cervical cancer in a multicenter retrospective analysis. Chen et al (32) demonstrated that NAC reduced the probability of lymph node metastasis for patients with stage IB1-IIB uterine cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…However, the prognosis of these patients remains unfavorable, suggesting that improvements in the available treatments are required. Effective NAC treatment has been reported to reduce the tumor size, allow patients to undergo hysterectomy and potentially improve patient prognosis (7,8). However, if NAC is ineffective, there are currently no alternatives to surgical resection other than radiotherapy, which may lead to unfavorable prognosis due to the delay in the initiation of core treatment (35).…”

Section: Discussionmentioning

confidence: 99%

“…However, compared with patients with early-stage disease, the prognosis of these patients is unfavorable, with a 5-year survival rate of <60% (5,6). Reducing the tumor size by administering neoadjuvant chemotherapy (NAC) was indicated to facilitate the success of hysterectomy, resulting in improved prognosis (7,8); therefore, the use of NAC for the treatment of cervical cancer has attracted significant attention in recent years (8). However, if NAC fails to sufficiently reduce the tumor size to perform hysterectomy, the treatment strategy is altered to radiation therapy, which delays the initiation of core treatment and results in unfavorable prognosis (9,10).…”

Section: Introductionmentioning

confidence: 99%

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T‑box 2 expression is a useful indicator of the response to neoadjuvant chemotherapy for patients with locally advanced uterine cervical squamous cell carcinoma

et al. 2021

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Platinum-based concurrent chemoradiotherapy is the standard treatment for patients with locally advanced uterine cervical squamous cell carcinoma. Reducing the tumor size by administering neoadjuvant chemotherapy (NAC) is beneficial for successful hysterectomy, resulting in a more favorable prognosis. Therefore, identifying biomarkers that predict the effectiveness of NAC in patients with cervical squamous cell carcinoma remains a priority. Cancer cells widely express T-box 2 (TBX2), which contributes to the resistance to DNA-damaging chemotherapeutic agents. The present study aimed to determine the association between TBX2 protein expression in tumor tissues and the efficacy of NAC in locally advanced uterine cervical squamous cell carcinoma using immunohistochemistry. Data from 46 patients with locally advanced uterine cervical squamous cell carcinoma were classified into two groups based on their effective or ineffective response to NAC treatment. In addition, the effect of small interfering RNA-mediated knockdown of TBX2 on the sensitivity of cervical cancer cells to cisplatin was investigated in vitro. The results revealed that there were no significant differences in patient clinicopathological features between the NAC effective and NAC ineffective groups. The overall survival of the NAC effective group was significantly improved compared with the NAC ineffective group (P=0.007). Tumors from the NAC effective group also had significantly downregulated TBX2 expression levels compared with those from the NAC ineffective group (P=0.0138). Of note, decreased TBX2 expression was indicated to be significantly associated with higher sensitivity to NAC (P=0.009). The low TBX2 expression group had a more favorable overall survival compared with the high TBX2 expression group (P=0.049). Furthermore, knockdown of TBX2 expression significantly increased cancer cell sensitivity to cisplatin in vitro. In conclusion, the results of the present study suggested that TBX2 expression may be a useful predictor of the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma.

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“…Neoadjuvant chemotherapy (NAC) followed by surgery is considered one of the treatment options for patients with locally advanced uterine cervical cancer, even though its value remains contested. NAC has the potential to reduce the tumor size and allow for a hysterectomy for patients with stages IIIB-IVA uterine cancer in which hysterectomy is normally not possible, and this course can improve a patient's prognosis (4)(5)(6). However, if the NAC treatment does not effectively shrink the tumor size, the patients instead have to undergo radiotherapy, and this delays the initiation of the core treatment, and thus a worse prognosis.…”

Section: Introductionmentioning

confidence: 99%

Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy

et al. 2022

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Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer.

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Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis

Cited by 11 publications

References 21 publications

Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future

Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future

T‑box 2 expression is a useful indicator of the response to neoadjuvant chemotherapy for patients with locally advanced uterine cervical squamous cell carcinoma

Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy

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