Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons

Peritoneal surface malignancies (PSM) represent an advanced form of abdominal malignancies associated with a dismal prognosis which including gastric, colorectal, ovarian, peritoneal mesothelioma, and pseudomyxoma peritonei. Many patients have been treated with palliative surgical debulking procedures followed by systemic chemotherapy only [1]. However, the success of this treatment modality has been limited by peritoneal penetration [2]. Although PSM is categorized as a metastatic peritoneal disease, it may represent a special locoregional disease pattern limited to the abdominal cavity. Cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) have been used as the standard locoregional treatment for selected patients with PSM [3, 4]. In well-selected patients with an acceptable disease burden, the multimodal modality of CRS with HIPEC may offer an extended survival compared to standard systemic chemotherapy or no treatment [5, 6]. However, given the perceived and well-recognized morbidities, the lack of widespread acceptance, adoption, and accessibility associated with CRS/HIPEC remain a significant challenge, even in recent inquiries [7, 8].

A few guidelines have been created to optimize the benefits and minimize the morbidity for patients with PSM [9, 10]. However, the treatments for PSM are complex and heterogeneous and require institutional support [11]. Therefore, actual practice protocols vary according to each surgeon’s preference despite general guidelines established from consensus obtained through a Delphi process. The standardization of clinical practice guidelines is paramount in improving patient selection, perioperative morbidity, and completeness of cytoreduction [12, 13].

The goal of this study was to investigate the variations in clinical practice of CRS with HIPEC among oncologic surgeons from different countries and to assess their opinions surrounding this therapeutic modality.

From September to October 2016, an online questionnaire surveyed by the corresponding authors from various countries from published manuscripts on CRS with HIPEC and to the members of the Korean Society of PSM (KSPSM). The questionnaire was received from only one respondent per team. An English-language survey was developed by the authors and was made available online for anonymous submission using a web-based survey service (SurveyMonkey (R), Palo Alto, CA, USA). The full survey is available in Additional file 1. Surgeons were requested by email to complete the survey within a 4-week period, and approval was obtained from the institutional review board of the primary site (CNUH 2017-01-034-002). The questionnaire included 20 multiple-choice questions to assess the opinions of the responders; their criteria for patient selection; and eligibility for CRS with HIPEC, modes of perioperative staging, level of surgery skills, residual tumor assessment, and method used for HIPEC administration. A reminder was sent to non-respondents 3 to 4 weeks following the initial mailing of the questionnaire. The closing date of the survey was October 2016, and the results were analyzed. A descriptive analysis was performed. A subgroup analysis of the experience of CRS/HIPEC and hospital volume of the responders was performed using the T test for continuous variables (or the Kolmogorov-Smirnov test when the expected frequency within any cell was less than 5) and the χ²—test (or Fisher’s exact test when the expected frequency within any cell was less than 5) for the categorical variables.

Our study indicated that diffuse mesenteric invasion is the most crucial factor impacting the treatment decision for PSM. Approximately half of the respondents indicated that a poor ECOG performance status and portal vein invasion were the second and third factors, respectively, as challenges against the use of CRS with HIPEC. Previous studies have reported that high-volume surgeons could produce favorable oncologic outcomes and reduce adverse events [13, 15, 16]. The present study showed that surgeons who have performed at least 50 cytoreductive surgeries encountered fewer obstacles perioperatively and morbidities, and revealed that the volume of the medical institutions may not be the critical factor.

There was no doubt that the number of experienced CRS/HIPEC by the surgeons was one of the important factors for the treatment outcomes of PSM. However, Gary et al. reported that even low-volume experiences with CRS/HIPEC can lead to a reduction in adverse perioperative events with acceptable oncologic outcomes [17]. In addition, Cliby et al. reported that CRS was greatly influenced by surgical effort, and the rate of optimal cytoreduction was depended upon surgeon tendency [18], which implies that the individual surgeon’s skills and effort may be as important as the experiences of the surgeon in the oncologic outcomes of CRS. In order to achieve the optimal outcome, all surgeons that perform CRS/HIPEC were expected to have received proper training and asked to strictly follow the guidelines.

CRS and HIPEC have been shown to improve survival in selected patients with PSM, and it can be considered as the standard of care for this specific disease entity [19, 20]. Despite its widespread use in clinical practice, CRS with HIPEC continues to be perceived by a sizable proportion of the surgical community as experimental, possibly related to a lack of inclusion in clinical practice guidelines [9]. In this study, most surgeons used an FDA-authorized or a commercially available machine during HIPEC. However, current practices regarding infusion temperature during HIPEC have widely varied. While half of the surgeons used 42°, t temperatures ranged from 41, 43, 40, and over 43 °C (18, 18, 6, and 6%, respectively). The HIPEC perfusion time is also different, with approximately half of the surgeons indicating 90 min while others preferred a treatment time of 60, 30, and 120 min (48, 30, and 19%, respectively). Likewise, inconsistencies in the various technical practice patterns may significantly impact the clinical outcomes. Despite the complexity of PSM, a standardization of practice protocols must be formulated.

We demonstrated that most surgeons used the Sugarbaker’s staging system to intraoperatively measure the extent of peritoneal invasion. However, a few others use their own non-standardized peritoneal carcinomatous index. Furthermore, clinicians are using different methods to measure the residual tumor size. Most responders measured the size of the entire clustered group as one tumor while others individually measured the size of each tumor nodule. The methods to standardize perioperative staging are paramount.

Although the originally described closed technique is limited by a lack of direct control to the abdominal cavity, resulting in a suboptimal homogeneous distribution of the perfusate, it may provide the highest level of protection for the operating room staff. In this study, almost all respondents used the closed method. However, there is also no standard protocol described for HIPEC using the closed method. Approximately half of the surgeons who selected HIPEC with a closed method first sutured the skin closed, performed HIPEC, followed by re-opening of the abdomen for final assessment and closure. Other methods used include various permutations of the closed method. Further studies are needed to evaluate which strategy of the closed method would maximize clinical outcome, efficiency, and safety for the operating staff.

The limitations of this study include the potential for self-reported bias. The sample size was small and exhibited heterogeneity. Our results should be further verified in future studies using a large prospective cohort. Despite these limitations, this study warrants the importance of further large-scale studies to evaluate and subsequently recommend clinical guidelines for CRS with HIPEC in the treatment of PSM. Although CRS with HIPEC is currently the recommended treatment for PSM, practices vary widely. Therefore, the standardization of clinical practice protocols will provide an opportunity to improve patient outcomes.

The CRS and HIPEC have been used as the standard treatment for selected patients with PSM. However, the clinical practices of CRS with HIPEC are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.