Peritoneal metastases from extra-abdominal cancer – A population-based study

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Abstract

Introduction

Peritoneal metastases (PM) are predominantly seen as a manifestation of intra-abdominal malignancy such as colorectal or ovarian cancer. However, extra-abdominal primary cancer can also metastasise to the peritoneum. Population-based data on the incidence of PM from extra-abdominal cancer is lacking. This study aims to assess the patterns and survival of patients in Ireland with PM from extra-abdominal cancers.

Methods

The National Cancer Registry of Ireland database was interrogated to identify patients diagnosed with PM from extra-abdominal malignancy during the period 1994–2012. Patient demographics and tumour characteristics were analysed.

Results

5791 patients were diagnosed with PM during the study period. Of these, 543 (9%) had an extra-abdominal primary malignancy. Breast (40.8%), lung (25.6%) and melanoma (9.3%) were the most common extra-abdominal cancers to develop PM. The majority of patients with peritoneal metastases of breast origin (75%) were diagnosed at a long interval (median interval 59.5 months; range = 1–485) from the diagnosis of the primary. The median survival from diagnosis of PM was 5.8 months compared with 22.6 months from diagnosis of stage IV disease without peritoneal involvement. Survival in patients with lung cancer and melanoma who developed PM was very poor and similar to that in patients with stage IV disease not involving the peritoneum.

Conclusion

This is the first population-based study to report the incidence of PM secondary to extra-abdominal malignancy. The most common primary cancers were melanoma, breast and lung cancer. Metastatic disease to the peritoneum was uniformly associated with a poor prognosis.

Introduction

Peritoneal metastases (PM) predominantly arise in patients with colorectal, appendiceal, gastric or ovarian cancer. Approximately 5% of patients with colorectal cancer, 9% of patients with pancreatic cancer and 46% of women with ovarian cancer are diagnosed with PM at initial presentation (synchronous PM) [1], [2], [3]. While PM can arise from extra-abdominal primary cancers, such cases are uncommon and the true incidence is unknown. To date, primary breast and lung cancers are the most commonly reported extra-abdominal malignancies resulting in PM [4], [5], [6].

Peritoneal metastases from intra-abdominal primary tumours are thought to result predominantly from loco-regional rather than systemic spread [7]. A commonly accepted theory is the ‘coelomic theory’ in which serosal invasion leads to gravitational pooling of tumour cells and pelvic implants, subphrenic implants from clockwise directional flow of the peritoneal fluid, and eventually omental caking from phagocytic activity of the omentum [8]. To date, the pathophysiology of peritoneal metastases from extra abdominal primary tumours are less well understood.

PM is generally a terminal development, with an average overall survival of less than 6 months [9], [10], [11]. The true incidence and prevalence of extra-abdominal primary malignancies metastasising to the peritoneal cavity has not yet been well described in the literature. Despite recent advances in surgical techniques and chemotherapeutics in a subset of patients with PM, mainly from primary colorectal, appendiceal or ovarian cancers [9], [12], [13], [14], [15], [16], [17], [18], the paucity of clinical trials specifically focusing on PM demonstrates the need for further research to advance the development of novel targeted therapeutic strategies. A pivotal initial step in this process is the need for population based data to document the incidence, and outcomes, of patients with PM.

The aim of this study is to assess the pattern of disease and survival in Irish patients with PM from extra-abdominal malignancies.

Section snippets

Methods

The National Cancer Registry Ireland (NCRI) is a statutory body responsible for the registration of all cancers within the Republic of Ireland since 1994, encompassing a population of over 4 million inhabitants. Although the reporting of cancer is not yet mandatory in Ireland, the NCRI, through hospital-based tumour registration officers, makes considerable efforts to ensure the completeness of recording of all invasive and in situ cancers and completeness of registration is estimated at 97%

Statistical analysis

Statistical analysis was performed using SPSS 18.0 software (Chicago, Il). Survival outcome were analysed using Kaplan-Meier estimates. Differences in survival were compared using the logrank test. A p value of <0.05 was considered statistically significant.

Patients

Five thousand seven hundred and ninety one patients were diagnosed with PM between 1994 and 2012 inclusive. The annual incidence of PM diagnosis increased from 228 in 1994 to 401 in 2012. Of the 5791 patients, 543 (9.4%) had an extra-abdominal primary malignancy.

The extra-abdominal primary cancers which most commonly spread to the peritoneum were breast cancer (n = 222/543, 40.8%), lung cancer (n = 139/543, 25.6%) and malignant melanoma (n = 51/543, 9.3%). These cancers accounted over three

Discussion

This study is the first to provide detailed national population-based data on the incidence and survival of patients with peritoneal metastases (PM) from extra-abdominal primary tumours. Breast cancer, lung cancer and malignant melanoma are the most common extra-abdominal causes of PM. PM was diagnosed in 0.5% of the total population (n = 41,789) of patients diagnosed with breast cancer during the study period. This finding is slightly lower than previously published rates of 0.7%–2.7% [21],

Conclusion

The current study has shown that extra-abdominal cancers account for approximately 10% of diagnosed cases of peritoneal metastases. Breast cancer, lung cancer, and malignant melanoma are the most common cancers to spread to the peritoneum. There may be a significant latency between initial cancer diagnosis and the development of PM, particularly for breast cancer. Once established PM is however invariably and rapidly fatal. PM from extra abdominal malignancy presents an increasing challenge for

Disclaimer

The authors received no funding or financial assistance.

Declaration of interest

The authors have no disclosures or conflicts of interest to declare.

Novelty and impact

This is the first population-based study to report the incidence and outcomes for peritoneal metastases of extra abdominal origin. Peritoneal metastases of extra abdominal origin account for a significant proportion of the total number of patients diagnosed with PM, and survival is poor. These findings highlight the need for greater clinician awareness and the need to focus on new therapeutic approaches to improve patient outcomes.

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