Effect of neoadjuvant chemotherapy on platinum resistance in stage IIIC and IV epithelial ovarian cancer

Abstract

It remains controversial whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) induces chemoresistance in advanced epithelial ovarian cancer (EOC) compared with primary debulking surgery (PDS). The aim of this study was to compare platinum-resistant recurrence following treatment with NACT-IDS or PDS in patients with stage IIIC and IV EOC.We retrospectively reviewed the records of 341 patients who underwent PDS or NACT-IDS for Federation of Gynecology and Obstetrics stage IIIC or IV EOC between March 1990 and December 2010. Risk factors of platinum resistance, including NACT, postoperative residual tumor size, and various clinicopathological factors, were evaluated by univariate and multivariate logistic regression analyses. Survival analysis was performed by the Kaplan–Meier method and Cox regression modeling to measure overall survival (OS).Of 341 patients, 58 (17.0%) underwent NACT-IDS and 283 (83.0%) were treated with PDS. Twenty-nine (50.0%) patients developed platinum-resistant disease at first relapse after NACT-IDS and 99 (35.0%) patients recurred after PDS (P = 0.033). In the multivariate logistic regression analyses, NACT-IDS and postoperative residual tumor mass >1 cm were risk factors for platinum-resistant recurrence (adjusted odds ratios 2.950 and 2.915; 95% confidence intervals [CIs] 1.572–5.537 and 1.780–4.771, P = 0.001 and 0.000, respectively). Postoperative residual tumor mass >1 cm and platinum-resistant disease were significantly correlated with shorter OS (adjusted hazard ratios 1.579 and 4.078; 95% CI 1.193–2.089 and 3.074–5.412, P = 0.001 and 0.000, respectively), whereas NACT-IDS did not extend OS.NACT-IDS increases the risk of platinum-resistant recurrence in patients with stage IIIC and IV EOC.

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

“…If correct, this hypothesis predicts that the time to treatment resistance and disease progression will be shorter in patients receiving neo-adjuvant therapy as compared to those that have primary de-bulking surgery. Published clinical trials support this prediction [87, 90]. We further validate this hypothesis with our syngeneic carboplatin-resistant ovarian cancer model; we show that simply removing TRPV1 sensory nerves (TRPV1-DTA mouse) is sufficient to sensitize tumors to carboplatin therapy and improve survival.…”

“…Moreover, recurrent disease is more prevalent in patients that are neo-adjuvant treated as opposed to those that receive up-front surgical de-bulking [86]. Importantly, one study shows that neo-adjuvant therapy increases the risk of platinum-resistant recurrent disease at late stage [87]. These findings together with our data suggest that chemotherapy modulates sEV cargo such that robust innervation of residual disease ensues that may ultimately contributes to platinum-resistant recurrent disease.…”

Preoperative serum levels of HE4 and CA125 predict primary optimal cytoreduction in advanced epithelial ovarian cancer: a preliminary model study

“…The 5-year survival rate is less than 30% [1]. Residual lesions after primary surgery remain one of the most important prognostic factors in patients with advanced ovarian cancer [2][3][4][5].…”

Prognostic significance of platelet‐to‐lymphocyte ratio in patients with ovarian cancer: A meta‐analysis

“…Around the world, there were an estimated 200 000 new diagnosed cases and 150 000 deaths of cancer per year. [6][7][8] Therefore, the overall prognosis of patients with ovarian cancer remains poor. 3,4 Although cytoreductive surgery and platinum-based chemotherapy were applied routinely, most cases would turn into platinum resistance and disease progression with poor long-term survival.…”

“…5 In addition, approximately half of the patients will relapse within 1 year. [6][7][8] Therefore, the overall prognosis of patients with ovarian cancer remains poor. It is therefore vital to identify more effective and convenient prognostic factors to estimate prognosis and select appropriate treatment strategies.…”