Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer

Munetaka Takekuma,Shiho Kuji,Aki Tanaka,Nobutaka Takahashi,Masakazu Abe,Yasuyuki Hirashima 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.3

Objective: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. Methods: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. Results: In total, 49 patients―34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)―were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). Conclusion: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross- resistance of cisplatin analogue with cisplatin.

Challenges and perspectives on less invasive surgery for early-stage cervical cancer: a critical analysis of the SHAPE trial and its implications

Munetaka Takekuma 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.2

Cer vical cancer represents a global public health issue, particularly burdening many low-incomeand middle-income countries. Effective inter ventions, such as vaccination against thehuman papillomavirus and screening, render cer vical cancer a preventable disease [1]. By implementing these inter ventions, the incidence of cer vical cancer can be reduced,simultaneously enhancing the quality of life for cancer sur vivors, particularly those in theearly stages. Currently, the standard treatment for cer vical cancer is surger y with radicalhysterectomy (RH), which can lead to complications such as urinar y incontinence. The SHAPE trial results have been published in the New England Journal of Medicine [2], generatingenthusiasm among patients with early-stage cer vical cancer and gynecologic oncologists. The trial demonstrated that less invasive surger y is non-inferior to standard surger y for low-riskpatients. The trial results demonstrate that a lot of patients with early-stage cer vical cancer cansur vive with a good quality of life in clinical practice. However, I am composing this articledue to certain concerns regarding this trial. First, there are concerns related to the quality assurance of the surgical procedures. This trial excels in terms of external validity, specifically in terms of study generalization. However, doubts arise when considering whether the trial was conducted with adequateinternal validity. A crucial issue related to this trial is the quality assurance of the trial inter vention, i.e.,surgical therapy. To what extent was quality assurance implemented for RH or surgicaltherapy? Upon reviewing the trial results, in the RH group, there were 9 cases (2.7%) withpositive vaginal margins, which is higher than the expected occurrence rate. The studyincluded low-risk patients alone based on preoperative assessment. Considering thefrequency of positive vaginal margins when performing RH on the eligible trial participants,questions arise regarding the quality assurance of surgical therapy. For quality assurance,an audit of surgical therapy is crucial, and central review through photographs (or videos)should be considered mandator y. In particular, did the trial manager ensure that thecomponents deemed essential for RH, as outlined in the trial protocol, were appropriatelyperformed in the standard treatment group? According to the protocol, the followingprocedures are specified for RH: the en block removal of the uterus, cer vix, medial one-thirdof parametria, 2 cm of the uterosacral ligaments, and upper 1–2 cm of the vagina, the ligationof uterine arteries lateral to the ureters, and the unroofing of ureters from the ureterovesical junction. If these techniques were not adequately conducted, the trial could not evaluate itsoriginal research question, which means the trial may inadvertently compare “hysterectomy-mimicked RH” to simple hysterectomy. In the SHAPE trial, only photographic images of thesurgical specimen were requested for quality assurance [2], which may not be sufficient. Considering these factors, although the external validity is somewhat lacking, it might havebeen prudent to conduct the trial by limiting participating facilities and surgeons to enhancethe internal validity. Secondly, there are concerns about the primar y endpoint and non-inferiority margin. The primar y endpoint was changed from pelvic relapse-free sur vival to pelvic recurrence rateat 3 years (PRR3) due to the ver y low event rate. However, the choice of the primar y endpointas PRR3 raises concerns. Can we assert the establishment of surrogacy for the essentialultimate goal of cancer treatment, i.e., overall sur vival, based on PRR3? It is questionablewhether sufficient obser vation has been conducted for cases with an obser vation period<3 years. Furthermore, the outcomes may var y depending on the number of patients lostwithin the 3-year period and how they were labeled in the process of analysis. Additionall...

The relationship between positive peritoneal cytology and the prognosis of patients with FIGO stage I/II uterine cervical cancer

Shiho Kuji,Yasuyuki Hirashima,Satomi Komeda,Aki Tanaka,Masakazu Abe,Nobutaka Takahashi,Munetaka Takekuma 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.2

Objective: The purpose of this study was to assess whether peritoneal cytology has prognostic significance in uterine cervical cancer. Methods: Peritoneal cytology was obtained in 228 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics [FIGO] stages IB1-IIB) between October 2002 and August 2010. All patients were negative for intraperitoneal disease at the time of their radical hysterectomy. The pathological features and clinical prognosis of cases of positive peritoneal cytology were examined retrospectively. Results: Peritoneal cytology was positive in 9 patients (3.9%). Of these patients, 3/139 (2.2%) had squamous cell carcinoma and 6/89 (6.7%) had adenocarcinoma or adenosquamous carcinoma. One of the 3 patients with squamous cell carcinoma who had positive cytology had a recurrence at the vaginal stump 21 months after radical hysterectomy. All of the 6 patients with adenocarcinoma or adenosquamous carcinoma had disease recurrence during the follow-up period: 3 with peritoneal dissemination and 2 with lymph node metastases. There were significant differences in recurrence-free survival and overall survival between the peritoneal cytology-negative and cytology-positive groups (log-rank p<0.001). Multivariate analysis of prognosis in cervical cancer revealed that peritoneal cytology (p=0.029) and histological type (p=0.004) were independent prognostic factors. Conclusion: Positive peritoneal cytology may be associated with a poor prognosis in adenocarcinoma or adenosquamous carcinoma of the uterine cervix. Therefore, the results of peritoneal cytology must be considered in postoperative treatment planning.