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Resection Therapy Outcomes In Ovarian Metastases

Resection Therapy Outcomes In Ovarian Metastases

Overview

This study aimed to elucidate the significance of resecting ovarian metastases from colorectal cancer and identify relevant clinicopathologic characteristics.

Conducted retrospectively across 20 centers in Japan from 2000 to 2014, the study assessed data from 296 patients with ovarian metastases. The 3-year overall survival rate was 68.6% for solitary ovarian metastases.

Notably, curative resection demonstrated a 3-year overall survival rate of 65.9%, compared to 31.8% for noncurative resection and 6.1% for nonresection.

Multivariate analysis identified several prognostic factors, including the size of ovarian metastasis, bilateral involvement, peritoneal and pulmonary metastases, liver metastasis, and the presence of remnant ovarian metastasis.

The findings emphasize that both curative and noncurative resection of ovarian metastases confer a survival benefit, with prognostic factors centered around the characteristics of the metastases.

Introduction

Colorectal cancer (CRC) poses a significant global health burden, ranking third in new cases worldwide. Among the complications associated with CRC, ovarian metastasis is observed in approximately 1.1%–4.2% of affected women, contributing to substantial morbidity and mortality.

The median survival for individuals with ovarian metastasis from CRC ranges from 19 to 27 months, highlighting the urgency to understand and address this specific aspect of the disease.

 

Despite notable progress in chemotherapy, particularly with molecular-targeted therapy, ovarian metastases exhibit lower responsiveness to treatment compared to other metastatic sites. The ovary is characterized as a “sanctuary for metastases,” emphasizing the need for surgical intervention.

Surgical resection becomes crucial even in the presence of extraovarian metastases. However, the pathways leading from CRC to ovarian metastasis are not fully elucidated and may involve various mechanisms such as direct invasion, peritoneal dissemination, hematogenous spread, or lymphatic metastasis.

The classification of ovarian metastasis as distant metastasis (M) in both the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) and TNM systems underscores its severity.

However, a historical discrepancy existed, as the Japanese classification previously categorized it as peritoneal metastasis.

 

Existing literature on ovarian metastases often relies on small sample sizes from single institutions, resulting in a lack of robust data regarding clinicopathologic characteristics, prognosis, and the efficacy of treatments.

This study seeks to address these gaps by conducting a multicenter and retrospective analysis. It aims to provide comprehensive insights into the clinicopathological features of ovarian metastasis from CRC, shed light on prognosis, and clarify the significance of ovarian resection in its management.

The controversial aspects surrounding treatment strategies, including prophylactic and palliative ovarian resection, will be systematically explored, contributing valuable knowledge to the global discourse on CRC management.

 

Methods

This retrospective study, conducted across 20 institutions in Japan, aimed to investigate the significance of resection in cases of ovarian metastases from colorectal cancer (CRC) and identify relevant clinicopathologic characteristics.

The study, approved by the Ethics Committees of the Japanese Society for Cancer of the Colon and Rectum (JSCCR) and the Institutional Review Boards of participating hospitals, adhered to the Declaration of Helsinki.

Patients diagnosed with ovarian metastasis from CRC between 2000 and 2014 were included, and the study protocol was registered with the University Hospital Medical Information Network Clinical Trial Registry.

 

Data were collected retrospectively from medical records, encompassing information such as age, primary tumor details, histology, TNM classification, distant metastasis sites, preoperative serum markers, treatment interventions, and survival outcomes.

The primary outcome was the survival period after the diagnosis of ovarian metastasis, categorized into curative resection, noncurative resection, or nonresection. Secondary outcomes included the assessment of prognostic factors, clinicopathological characteristics, and the survival of solitary ovarian metastases.

 

The study employed well-defined criteria for curability, distinguishing between Curability A (no distant metastasis and no residual tumor), Curability B (not corresponding to A or C), and Curability C (macroscopic residual tumor).

Curative resection involved the complete removal of the ovarian metastasis, while noncurative resection aimed at symptom management or cytoreduction, with the possibility of remaining distant metastases.

Nonresection referred to cases where ovarian metastases were not surgically removed. Remnant ovarian metastases, denoting unresected cases, included those not treated with chemotherapy.

In-depth analyses sought to elucidate the impact of these variables on overall survival, providing valuable insights into the management and outcomes of ovarian metastases from CRC.

 

Statistical Analysis

The study presents its statistical methodology and analysis approach. Continuous data, expressed as median (range), and categorical data, presented as numbers (%), underwent comparison using the Mann–Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables.

The primary outcome, overall survival (OS) interval, was calculated from the diagnosis of ovarian metastasis (synchronous or metachronous) to the date of death, employing the Kaplan–Meier method for survival curve estimation and the log-rank test for comparisons.

 

Significant variables identified in univariate analyses were included in a Cox proportional hazards model. The model results were reported as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

A significance threshold of P < 0.05 was adopted for statistical significance.

The statistical analyses were carried out using EZR, a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria, v. 2.13.0), enhancing accessibility and usability in statistical procedures.

 

Results

In a retrospective study spanning the years 2000 to 2014, a comprehensive examination was conducted across 20 medical institutions in Japan to unravel the intricacies surrounding ovarian metastases from colorectal cancer (CRC).

Out of 20,841 female patients who underwent CRC surgery during this period, 296 cases of ovarian metastasis were identified, amounting to an estimated incidence of 1.4%.

The meticulous analysis of clinicopathological characteristics shed light on the nuances of primary tumors, illustrating that the majority of patients predominantly had colon or rectosigmoid cancer, with adenocarcinoma being the predominant histological finding in 81.8% of cases.

 

Digging deeper into primary tumor features, it was observed that nearly 90.9% of the cases were classified as T3/T4, signifying the extent of tumor invasion.

Lymph node metastasis, detected in 69.9% of patients, added another layer to the complexity of these cases. The study also differentiated between synchronous and metachronous ovarian metastases, unraveling distinct patterns and challenges associated with each.

 

Turning attention to ovarian metastases, the investigation unveiled intriguing details such as the prevalence of bilateral involvement in 37.8% of cases and a median tumor diameter of 10 cm.

For cases with metachronous ovarian metastasis, the median duration of disease-free interval post-primary resection was found to be 13.1 months.

The significance of surgical intervention emerged prominently, with a substantial 85.1% of patients opting for resection, further categorized into curative and noncurative procedures.

 

The survival outcomes painted a nuanced picture, emphasizing the critical role of resection types. The 3-year overall survival rates were reported as 68.6% for solitary ovarian metastasis, 65.7% for synchronous, and 69.7% for metachronous metastasis.

The divergence in survival rates based on the type of resection underscored the impact of these interventions on patient outcomes. Specifically, curative resection demonstrated significantly better outcomes with a 65.9% 3-year survival rate, in stark contrast to noncurative resection (31.8%) and nonresection (6.1%).

 

Delving into the realm of recurrence post-curative resection provided valuable insights, with the peritoneum emerging as the most common site of recurrence, followed by the liver and lungs.

This multifaceted exploration of recurrence patterns added depth to the understanding of disease progression even after seemingly successful interventions.

 

Prognostic factors identified through univariate and multivariate analyses further enriched the narrative. Tumor size, bilateral ovarian metastasis, peritoneal and pulmonary metastasis, liver metastasis, and the presence of remnant ovarian metastasis were all delineated as significant predictors of shorter survival, contributing to a refined prognostic framework.

 

In essence, this retrospective study meticulously unveiled the intricate landscape of ovarian metastases from CRC, providing a holistic view of clinicopathological characteristics, treatment dynamics, and survival outcomes.

The findings underscore the multifaceted challenges posed by these metastases and illuminate the critical importance of tailored interventions to optimize patient outcomes.

 

Conclusion

This study investigates the prognosis of solitary ovarian metastasis in Stage IV colorectal cancer (CRC), whether synchronous or metachronous. With a 3-year overall survival (OS) rate of 68.6%, solitary ovarian metastasis presents a relatively optimistic outlook.

The research challenges the historical perspective on extraovarian metastasis, emphasizing the pivotal role of resection (curative or noncurative) as a significant prognostic factor.

Despite the resistance of ovarian metastases to chemotherapy, oophorectomy is highlighted as a potential strategy, enabling continued chemotherapy and potentially prolonging prognosis.

Bilateral oophorectomy is recommended, considering the recurrence risk in the contralateral ovary.

 

The study also questions the classification of ovarian metastasis as distant metastasis within the TNM system, proposing an association with peritoneal metastasis.

Characteristics like synchronous ovarian and peritoneal metastases suggest a clinicopathological link. The findings prompt considerations for a refined classification aligning with the JCCRC’s peritoneal metastasis framework.

Overall, the study contributes nuanced insights into managing ovarian metastases in CRC, advocating for tailored approaches to optimize outcomes.

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