This study reports the outcome of 8 PMP patients with very high PCI who were approached with a two-step surgical strategy in an attempt to reduce the postoperative morbidity and mortality associated with CRS for such an extensive disease. While one patient was deemed unresectable at the second surgery, complete CRS with HIPEC was feasible for 7 patients, with good oncological outcomes, reasonable morbidity and no mortality.
Patient selection can be challenging in PMP cases with very high PCI. Predicting resectability with preoperative imaging remains an issue[21] and the need to resect multiple organs or digestive segments [22] is particularly difficult to anticipate. Furthermore, extensive disease [23, 24], prolonged operative time and postoperative complications are all factors associated with long-term impairment of quality of life [10], which has to be considered when performing CRS and HIPEC for such patients. Since the only therapeutic alternatives are debulking and systemic chemotherapy, which are both palliative options [25], CRS and HIPEC in this population may be considered in a curative intent, but only if a complete CRS is achievable with acceptable postoperative morbidity and impact on quality of life.
Benhaim et al. [17] recently published a series of 68 PMP patients with extensive disease that underwent complete CRS with HIPEC in a single procedure, with a median PCI of 37. The mean operative time was 713 minutes, mean estimated blood loss was 1826 mL and mean hospital stay was 37 days. Finally, severe complications and mortality were reported in 46% and 8% of patients, respectively. In the present study, the two-step approach resulted in a median PCI reduction of 12 (33 to 21) between the two procedures, with a combined median operative time of 900 minutes, estimated blood loss of 1900 mL and hospital stay of 35 days. However, severe complications were reported in only 25% of patients with no mortality, which is consistent with morbidity rates (2.7–33%) and mortality rates (0-2.7%) reported in the literature [26] for all PMP patients, regardless of the PCI. We could hypothesize that in a two-step approach, operative outcomes are cumulative, but morbidity and mortality are not, with each procedure having its own risks and associated complications.
Only one other example of two-step approach for peritoneal surface malignancy has been reported in the literature. Leinwand et al.[27] reported a series of 204 cases of malignant peritoneal mesothelioma treated with a similar strategy. The first step consisted of an omentectomy and gross debulking, followed by the insertion of an intraperitoneal catheter for chemotherapy infusion in the postoperative course, with a planned second look. The second surgery was performed in 63% of the patients. HIPEC was delivered in 61% after the first CRS and 89% after the second CRS. Major complications were reported in 13% of patients after the first surgery and 10% after the second surgery. PCI was not reported. The median time between the two procedures was 5.4 months.
In this series, two patients had a recurrence. One patient presented with peritoneal recurrence at 9.3 months after a complete two-step surgery and underwent a third intervention consisting of CRS and mitomycin C HIPEC. This patient is still alive after 63 months of follow-up. Another patient presented with peritoneal recurrence at 16.6 months, but was deemed unresectable at exploratory laparotomy. Despite receiving palliative chemotherapy, the patient died at 66 months. For that patient, the initial histology of peritoneal metastases was low grade PMP, but revision of pathology slides later classified the disease as high-grade PMP. The aggressiveness of the disease was therefore higher than initially expected and might have been the cause of the unfavourable outcome. This highlights the fact that this two-step approach should probably be reserved for low-grade disease, as high-grade disease presents a higher risk of early reccurence[28].
Optimal timing for the second procedure has yet to be determined. The hypothesis is that the surgical risk of an early reoperation is outweighted by the risk of progression, as PMP is an indolent disease. The patient needs to recover completely from the first surgery. Complete resorption of the postoperative intrabdominal inflammatory response is necessary in order to proceed to second CRS. In this series, time between the two procedures ranged from 90 to 212 days and no patient was deemed unresectable because of an unresolved inflammatory response. However, one patient PMCA-I disease (PSOGI low-grade PMP) presented an early invasive pelvic recurrence after the initial surgery, with a time span of 4 months between the two procedures. Because of the early recurrence and overall extent of the disease, CRS and HIPEC were not performed. Palliative chemotherapy was started and the patient eventually died 39 months later. Having said that, it is noteworthy that the patient was symptomatic (bloating and abdominal discomfort) before his first surgery and felt much better after, without severe morbidity. In the recent guidelines published by PSOGI/EURACAN (European network for Rare Adults Solid Cancer)[26], tumor debulking was an accepted strategy for selected patients with unresectable low grade PMP, as it may improve quality of life with acceptable morbidity and mortality. Even though the patients undergoing the two-step approach are operated with a curative intent, the first step certainly reduces the bulkiness of the disease and may improve patients’ condition in a similar way than palliative tumor debulking.
This study is not without its limitations. This is a retrospective study and only a small number of patients could be included, as extensive PMP is a rare presentation of a rare disease. No group-control comparison was possible within our institution, since all PMP patients with very high PCI are approached with a two-step strategy. Future studies aiming to compare the outcomes of PMP patients with very high PCI after pairing them with patients from large international cohorts could be helpful.