Survival outcomes after delayed cytoreduction surgery following neoadjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: Interval cytoreduction following neoadjuvant chemotherapy is a well-recognized treatment alternative to primary debulking surgery in the treatment of advanced epithelial ovarian cancer where patient and/or disease factors prevent complete macroscopic disease resection to be achieved. More recently, the strain of the global COVID-19 pandemic on hospital resources has forced many units to alter the timing of interval surgery and extend the number of neoadjuvant chemotherapy cycles. In order to support this paradigm shift and provide more accurate counseling during these unprecedented times, we investigated the survival outcomes in advanced epithelial ovarian cancer patients with the intent of maximal cytoreduction following neoadjuvant chemotherapy with respect to timing of surgery and degree of cytoreduction. METHODS: A retrospective review of all patients aged 18 years and above with FIGO (2014) stage III/IV epithelial ovarian cancer treated with neoadjuvant chemotherapy and the intention of interval cytoreduction surgery between January 2008 and December 2017 was conducted. Overall and progression-free survival outcomes were analyzed and compared with patients who only received chemotherapy. Outcome measures were correlated with the number of neoadjuvant chemotherapy cycles and amount of residual disease following surgery. RESULTS: Six hundred and seventy-one patients (median age 67 (range 20-91) years) were included in the study with 572 patients treated with neoadjuvant chemotherapy and surgery and 99 patients with chemotherapy only. There was no difference in the proportion of patients in whom complete cytoreduction was achieved based on number of cycles of neoadjuvant chemotherapy (2-4 cycles: 67.7%, n=337/498); ≥5 cycles: 62.2%, n=46/74). Patients undergoing cytoreduction surgery after neoadjuvant chemotherapy had a median 5-year progression-free and overall survival of 24 and 38 months, respectively. No significant difference in overall survival between surgical groups was observed (interval cytoreduction: 41 months vs delayed cytoreduction: 43 months, p=0.52). Those who achieved complete cytoreduction to R0 (no macroscopic disease) had a significant median overall survival advantage compared with those with any macroscopic residual disease (R0: 49-51 months vs R<1: 22-39 months, p<0.001 vs R≥1: 23-26 months, p<0.001). CONCLUSIONS: Survival outcomes do not appear to be worse for patients treated with neoadjuvant chemotherapy if cytoreduction surgery is delayed beyond three cycles. In advanced epithelial ovarian cancer patients the imperative to achieve complete surgical cytoreduction remains gold standard, irrespective of surgical timing, for best survival benefit.

Analysis of prognostic variables, development of predictive models, and stratification of risk groups in surgically treated FIGO early-stage (IA-IIA) carcinoma cervix.

OBJECTIVES: The objectives of the study were to evaluate clinicopathologic prognostic variables in surgically treated International Federation of Obstetrics and Gynecology early-stage (IA-IIA) cervical cancer, develop prognostic models, and note the role of adjuvant treatment, patterns of failure, and salvage survival (SS) in each group. METHODS: Records of 542 patients who received primary surgical treatment for International Federation of Obstetrics and Gynecology (IA-IIA) cervical cancer were reviewed. Ninety-eight patients who relapsed after primary treatment were identified and matched for stage and age with a control group. Clinicopathologic prognostic variables were identified and used to develop a prognostic model with 3 risk groups for overall survival (OS) and relapse-free survival (RFS). The roles of adjuvant treatment, relapse sites, and SS were also noted in the groups. RESULTS: The 5-year OS was 70% for the whole group, 97% in the control group, and 44% in the relapse group. There was a statistically significant decrease in survival in patients 70 years or older, those with positive lymphovascular space invasion (LVSI), and in patients with positive LVSI and increasing depth of invasion in both univariate and multivariate analyses (P < 0.001). Positive lymph node status and tumor size of 31 mm or greater showed only a trend toward lower OS and RFS, respectively, in multivariate analysis. An additive model using regression coefficients from multivariate Cox model stratified patients into low-, medium-, and high-risk groups. Relapse-free survival and OS were significantly different in all 3 groups (P < 0.001). Salvage survival was better in low-risk group relative to medium- and high-risk groups, (P = 0.05) as well as between the medium- and high-risk groups (P = 0.03). More distant and locoregional relapses were noted in the medium- and high-risk groups, and SS was better with a local versus locoregional or distant recurrence (P < 0.001). CONCLUSIONS: In this study, age 70 years or older and positive LVSI were found to be statistically significant prognostic factors for both OS and RFS. Positive lymph nodes status showed only a trend toward lower OS. Positive LVSI status had significant adverse prognostic effects on RFS and OS in tumors with increasing depth of invasion. Additive prognostic model helps identify predictors and stratify patients into low-, medium-, and high-risk groups for survival. Many of these factors can be identified preoperatively and may assist in decision to offer primary surgery or alternative therapies in patients with potentially operable cervix cancer. Prognostic model can be used as a tool to design clinical trials and select the group of patients who are the appropriate target for a trial.

Neoadjuvant chemotherapy followed by radical vaginal trachelectomy and adjuvant chemotherapy for clear cell cancer of the cervix: a feasible approach and review.

BACKGROUND: Clear cell adenocarcinoma of the cervix (CCAC) may affect pediatric and younger women in absence of diethylstilbestrol exposure and other classic predisposing factors for cervical cancer. Prognosis is similar for early-stage CCAC, squamous cell cancer and non-clear cell adenocarcinoma of the cervix. Vaginal radical trachelectomy (VRT) and abdominal radical trachelectomy (ART) with pelvic lymph node dissection have evolved as valuable fertility-preserving treatment options. Neoadjuvant chemotherapy (NACT) before abdominal radical trachelectomy/VRT may reduce tumor size and thereby facilitate surgery. In some cases, adjuvant treatment in the presence of high-risk prognostic features may be required to optimize treatment. METHODS: A 13-year-old adolescent with International Federation of Obstetrics and Gynecology stage IB1 CCAC was treated with NACT using carboplatin and paclitaxel (CP) followed by laparoscopic pelvic lymphadenectomy, VRT, and adjuvant chemotherapy. RESULTS: Neoadjuvant chemotherapy using CP was well tolerated with no toxicity. Neoadjuvant chemotherapy reduced the tumor size and facilitated radical vaginal trachelectomy. Adjuvant treatment was recommended in the presence of risk factors. The patient elected to conserve the uterus and underwent 3 further cycles of adjuvant chemotherapy with CP. CONCLUSIONS: This is the first reported case of CCAC treated with NACT using CP followed by laparoscopic pelvic lymphadenectomy, VRT, and adjuvant chemotherapy. A successful treatment outcome achieved using this novel approach suggests its applicability in selected cases.

Pyomyositis after chemotherapy for endometrial cancer.

Pyomyositis is a rare complication of chemotherapy that is commonly seen in tropical climates and in patients with immunodeficiency states. Owing to its rarity and subacute presentation, its diagnosis is often delayed. It has been reported after intense chemotherapy for hematological cancers. We present a case of a 58-year-old woman with endometrial cancer who developed pyomyositis after the first cycle of carboplatin and paclitaxel with no prior predisposing factor except for cancer and premedication with corticosteroids. The patient improved once the diagnosis was established and managed with antibiotics and drainage of abscess. Full recovery was made with a protracted course of antibiotics.Early diagnosis of this entity with appropriate investigations and treatment prevents septicemia, which can often be life threatening.

Hormone replacement after gynaecological cancer.

Treatment of gynaecological cancer frequently results in the loss of ovarian function and menopausal symptoms. Symptoms of iatrogenic menopause are usually significantly more intense than those of natural menopause due to sudden onset of symptoms, younger age and its effects on common physical and psychological problems of cancer therapy like body image concerns and sexual dysfunction. The most effective treatment for menopausal symptoms is hormone replacement therapy (HRT). However, it is very controversial if HRT is safe in patients after a gynaecological malignancy. The main concerns are the potential stimulation of residual cancer and the induction of new hormone-dependent disease. However, the majority of the most common gynaecological malignancies like squamous cell carcinomas of the cervix, serous papillary epithelial ovarian carcinomas and squamous cell carcinomas of the vulva are not oestrogen dependent. Furthermore, current scientific evidence does not show HRT to adversely affect the outcome in patients after treatment for hormone sensitive cancers like early stage endometrioid adenocarcinomas of the endometrium. There are only a small number of gynaecological malignancies like low grade endometrial stromal sarcomas in which HRT is an absolute contraindication. Therefore, as maintaining quality of life and minimising the physical and psychological impact of treatment side effects is one of the most important factors in cancer care, it is imperative to give patients unbiased information about their individual cancer which in most cases will allow them to use HRT without any detrimental effect on their survival.

Lethal endometrial recurrence after cone biopsy for microinvasive cervical adenocarcinoma.

The follow up of microinvasive cervical adenocarcinoma treated conservatively is difficult because recurrences are often out of range and Pap smears difficult to interpret. A 30-year-old woman with a microinvasive adenocarcinoma with clear, but narrow, margins on cone biopsy was treated conservatively. After 2 years of close follow up in which no recurrence was detected, dilatation and curettage performed for infertility revealed adenocarcinoma invading secretory endometrium. The carcinoma resembled her cervical adenocarcinoma histologically, immunohistochemically and was HPV DNA 16 positive. A radical hysterectomy showed carcinoma involving the entire endometrium and the uppermost 3 mm of the endocervical canal, but sparing the remainder of the cervix. The patient died of disseminated carcinoma at the age of 34 years. The location of the recurrence was the reason it escaped detection for so long despite close follow up.