Urological Procedures in Patients with Peritoneal Carcinomatosis of Colorectal Cancer Treated with HIPEC: Morbidity and Survival Analysis

Discussion

In the current study, we investigated the impact of combined urological procedures during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneally-metastasized colorectal cancer. Although patients with a urological procedure showed a significantly increased rate of postoperative morbidity and mortality, long-term and disease-free survival was not different between patients with or without urological procedures. The increased morbidity rate was probably mostly related to the extent of visceral resections, rather than the urological procedure by itself. As shown, postoperative morbidity predominantly consisted of gastrointestinal complications, i.e., gastrointestinal leakage, intra-abdominal abscess and fistula formation. Additionally, although the extent of peritoneal dissemination, measured by sPCI, was comparable between the groups, patients with urological procedures presented with more extensive locoregional recurrent disease requiring more visceral resections. Patients with a urological procedure had an increased rate of rectosigmoid resections, hysterectomies and partial small bowel resections most likely arising from their close anatomical relation.

Urological procedures were significantly more performed in patients with metachronous PC compared to patients with synchronous PC. An explanation for this phenomenon may be that retroperitoneal involvement of peritoneal metastasis may develop more frequently after prior surgical trauma, giving free floating tumor cells the possibility to reach the retroperitoneal plane (9).

Direct metastasis of colorectal cancer to the urogenital tract is rare and has only been described in case-reports or small case series (10). In contrast, primary tumor in-growth or locoregional or peritoneal metastases is more frequent. Accurate incidence data are currently not available. In our study, involvement of the urological tract was confirmed histopathologically in 21 patients (55%). This shows that it is difficult to preoperatively distinguish inflammatory adhesions between anatomical structures from malignant invasion. This is also demonstrated in other studies investigating en bloc resections of urological organs without HIPEC (11). In doubtful intraoperative situations, one often decides in favour of extended en bloc resections. This may result in a higher number of complete cytoreductions and better survival at the cost of more extensive resections with non-malignant definite pathology findings. Frozen section procedures are more often than not a helpful tool in this situation; in the future, intraoperative tumour-specific fluorescence imaging may possibly aid in a more accurate diagnosis of malignant and non-malignant adhesions and degree of peritoneal dissemination (12).

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Figure 1.

Kaplan-Meier survival curve following HIPEC in months, median OS: 32.1 versus 26.9 months.

The current study may be limited by its retrospective design, which precludes definite conclusions especially with regard to the post-operative mortality. To our knowledge, we reported on the largest cohort of urological procedures in exclusive colorectal cancer patients treated with CRS+HIPEC for peritoneal carcinomatosis. Four other studies have investigated the influence of an associated urological procedure during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (13-16). All these studies incorporated procedures for various primary malignancies. Between 7 and 20% of patients needed a urological procedure. Contrary to our study, all these reports concluded that urinary tract procedures at CRS+HIPEC do not increase postoperative morbidity and can be performed safely. Similar to our study, no adverse effect on the survival of patients treated with CRS+HIPEC was reported.

The rationale of hyperthermic intra-peritoneal chemotherapy is to eradicate residual tumor cells by cytotoxic chemotherapy. Inevitably the chemotherapeutic drugs also affect healthy tissues and impaired wound healing may occur. For instance, decreased strength of colonic anastomoses has been described in experimental models following hyperthermic intraperitoneal chemoperfusion with mitomycin or cisplatin (17, 18). The effect of hyperthermic intraperitoneal chemotherapy on the healing of urological anastomoses is currently unknown. In our study the number of urological leakages is limited (11%) and comparable to similar urological procedures without hyperthermic intraperitoneal chemotherapy (11).

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Figure 2.

Kaplan-Meier disease-free survival curve following HIPEC in months, median DFS: 14.5 versus 16.2 months.

In conclusion, cytoreductive surgery in combination with HIPEC in patients requiring urological resection, as part of the cytoreduction, is associated with significant postoperative morbidity and mortality, probably due to an overall more extensive cytoreduction. Urological procedures as a part of CRS+HIPEC can be performed safely, with limited urological-associated complications. Long-term survival was shown to be similar in patients with a urological procedure during CRS+HIPEC, compared to patients without additional surgery of the urinary system. Patients with peritoneal carcinomatosis with urologic involvement should be evaluated in an experienced peritoneal surface malignancy centre and treatment should be based on individual patient characteristics. Urological involvement of colorectal peritoneal metastases should not be regarded as an exclusion criterion in these patients.