Background
Peritoneal metastasis (PM) in patients with breast cancer (BC) and endometrial cancer (EC) is a rare and challenging condition. Patients with PM account for less than 3% of recurrent BC and EC cases [
1‐
4]. In a comprehensive review of the literature, only 21 articles with 505 patients with BC and PM were identified [
1]. Based on these data, PM was associated with invasive lobular histology, loss of functional p53, and loss of E-cadherin expression. BC patients with PM have a very poor prognosis. For example, in a retrospective series of 44 patients, the median survival from the diagnosis of BC and PM was only 1.5 months (range 0.2–27 months) [
2]. In analogy to patients with BC and PM, patients with EC and PM also have a poor prognosis [
5,
6]. In a French multicenter study with 1230 EC patients, for example, metachronous PM developed in less than 2% of cases [
7]. Patients with PM had significantly shorter survival times compared to EC patients with other recurrence pathways. In accordance, Ozkan et al. found that the 5-year progression-free survival rate of patients with EC and PM was 35% compared to 54% for patients with EC and vaginal vault recurrence [
8].
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a new technique to deliver intraperitoneal chemotherapy with the aim of achieving high local concentrations of chemotherapy compounds in the peritoneum [
9‐
13]. Recently, Alyami et al. summarized 45 clinical studies with 1810 PIPAC procedures in 838 patients [
14]. In this review, repeated PIPAC was feasible in 64% of patients with a 3% rate of intraoperative and postoperative surgical complications. Objective histological response was 62 to 88% for ovarian cancer, 50 to 91% for gastric cancer, and 71 to 86% for colorectal cancer. In this comprehensive review, however, no data on PIPAC in patients with BC and EC were identified. In addition, we performed a PubMed search (search terms: PIPAC, intraperitoneal chemotherapy, pressurized intraperitoneal chemotherapy, breast cancer, endometrial cancer; search date: April 8, 2020) and confirmed that there are no studies available reporting on PIPAC in patients with BC or EC.
During the last 7 years we established a comprehensive PIPAC program at our institution with clinical experience in > 1000 PIPAC procedures including patients with BC and EC [
15]. In order to address the feasibility, safety, and efficacy of PIPAC in patients with BC and EC, we identified all cases of PM from BC and EC treated with PIPAC in our institution and herein report the clinical results.
Discussion
PM in patients with BC and EC is associated with a poor prognosis and treatment options for this condition are limited. In a retrospective cohort study of patients with PM from BC and EC undergoing 150 PIPACs with doxorubicin and cisplatin, we found that this treatment was feasible and induced objective TRG in up to 55% of patients while maintaining quality of life. PIPAC induced no systemic toxicity and treatment-associated morbidity was acceptable with CTCAE grade 3/4 in 8% of procedures.
PIPAC is a new form of intraperitoneal chemotherapy for patients with PM from various origins, including BC and EC, where cytostatic drugs are laparoscopically delivered in the form of a pressurized aerosol rather than in liquid form during conventional intraperitoneal chemotherapy. This is thought to offer a number of advantages, supported by experimental evidence: increased surface/volume ratio of the aerosol droplets versus larger liquid volumes, better diffusion and influx by convection, as well as enhanced tissue penetration under pressure [
21,
22]. Furthermore, PIPAC can be applied repeatedly, providing the opportunity to obtain sequential tumor biopsies and PCI assessment, thus allowing the objective monitoring of therapy response. Safety and feasibility of PIPAC have been demonstrated in a number of studies on patients with mesothelioma, ovarian, gastric, pancreatic and colorectal cancer [
10,
12‐
15,
23‐
25]. We now confirm, for the first time, that PIPAC is also feasible and safe in patients with PM from BC and EC.
In our series, we encounterd a primary and/or secondary non-access of 5%, which is comparable to that observed by other groups [
10,
12,
26,
27]. The rate of postoperative complications (12 CTCAE grade 3/4 events in 150 PIPACs, some of which were unlikely to be procedure-related) was acceptable. Since the deepest tissue penetration, as demonstrated by ex-vivo studies [
28,
29], occurs in the small bowel, we did not perform adhesiolysis during PIPAC in order to avoid small bowel laceration. This might be one reason why there were no abdominal adverse events secondary to PIPAC.
Objective tumor regression was seen in > 70% of our patients with PM and major regression was achieved in more than 50% of patients. Matching up these findings with systemic chemotherapy outcomes reported by previous studies [
1‐
4] suggests PIPAC as a suitable therapy alternative. In addition, 30/44 patients had concomitant systemic chemotherapy or endocrine therapy, suggesting that PIPAC is also suitable in this patient population for a bidirectional therapy approach. This finding is in line with a recent report by Ploug et al. confirming the feasibility of bidirectional PIPAC and systemic chemotherapy in non-gynecological cancer patients [
27].
We found that PIPAC may preserve quality of life, as most functional scales such as the global health score, physical functioning, role functioning, emotional functioning, social functioning, and cognitive functioning had increased over time, while symptom scales of gastrointestinal toxicity (appetite loss, constipation, and diarrhea) were decreased. This is of note in such a population of patients with BC and EC, diagnosed with PM, that is treated with palliative intent and underscores the potential validity of PIPAC in such a setting.
Our study has limitations. The sample size is small, but this is usually the case when reporting on a rare disease such as PM in patients with BC and EC. As this is the first report on PIPAC in patients with BC and EC, our results must be independently confirmed. Furhtermore, the retrospective design of this study limits the internal validity of our study. Selection bias may have played a role because only fit patients were eligible for this therapy. Self-selection of patients may also have affected the results in favor of PIPAC. In addition, patients abandoning the therapy because of side effects or weakness also contribute to selection. However, these limitations also apply to studies evaluating palliative systemic chemotherapy. Prospecitve studies that avoid these limitations by applying uniform inclusion criteria should be carried out.
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