Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry

Our plain-English summary of Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry, by K.I. Votanopoulos, P. Sugarbaker, M. Deraco, et al (Annals of Surgical Oncology, 2018).

The study

• Authors: K.I. Votanopoulos, P. Sugarbaker, M. Deraco, D. Morris, O. Glehen, D. Elias, M. De Simone, M. Robella, B. Heyd, S. Kusamura, D. Baratti, K. Chouliaras, G. Russell, P. Shen, E.A. Levine, RENAPE Working Group
• Journal: Annals of Surgical Oncology
• Published: 2018;25(3):667-673
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant.

Methods: A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease.

Results: Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years; p = 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years; p = 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI; p = 0.015), CC status of resection (p < 0.0001), and Ki67 (p = 0.04) as predictors of survival. Systemic chemotherapy before (p = 0.55) or after (p = 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (p = 0.03) and CC (p = 0.04) remained significant.

Conclusions: Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.

In plain English

This was a retrospective analysis of an international registry of 1165 cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) procedures for peritoneal mesothelioma. The procedures were done at 33 centers in Australia, Europe and the US between 1990 and 2016. The authors compared survival after complete surgery in 450 epithelioid and 34 biphasic cases. Sarcomatoid cases were excluded. When no visible tumor was left (CC0), 5-year survival was 64.5% for epithelioid patients (208) and 50.2% for biphasic patients (22), with medians of 7.8 and 6.8 years. When surgery leaving residual disease under 0.25 cm (CC1) was added, 5-year survival was 62.9% versus 41.6%, with medians of 7.8 and 2.8 years. Among biphasic patients, more extensive disease and less complete surgery were linked to shorter survival. Chemotherapy before or after surgery was not a statistically significant predictor. The authors concluded that long-term survival is achievable in strictly selected biphasic patients with low-volume disease, only after complete macroscopic cytoreduction. They noted the limits of retrospective, multi-center data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of a multi-center international registry (Peritoneal Surface Oncology Group International) of surgical procedures
• Who was studied: 1165 CRS/HIPEC procedures for peritoneal mesothelioma at 33 centers in Australia, Europe and the US, 1990 to 2016. Analysis covered the 484 procedures (41.5%) with complete cytoreduction: 450 epithelioid and 34 biphasic. Sarcomatoid, well-differentiated papillary and cystic mesotheliomas were excluded.
• Exposure: The study examined a treatment, not an asbestos exposure: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), compared by mesothelioma subtype (epithelioid vs biphasic) and completeness of cytoreduction (CC0, CC1, CC2). Asbestos exposure was recorded only as a baseline characteristic.
• Main results:
  • After CC0 surgery (no visible residual disease), 5-year survival was 64.5% in epithelioid patients (n = 208) and 50.2% in biphasic patients (n = 22). Median survival was 7.8 and 6.8 years respectively (p = 0.015).
  • After CC0 surgery, 1- and 3-year survival were 93.5% and 70.6% in the epithelioid group. In the biphasic group they were 55.7% and 50.2%. Most deaths in the biphasic group occurred within the first 2 years.
  • With CC0 and CC1 surgeries combined, 5-year survival was 62.9% in epithelioid patients (n = 450) and 41.6% in biphasic patients (n = 34). Median survival was 7.8 and 2.8 years (p = 0.001 in the text; the abstract gives p = 0.0012).
  • Biphasic patients with CC1 surgery analyzed alone (12 patients) had a median survival of 2.8 years (33.9 months) and a 5-year survival of 33.3%.
  • Among biphasic patients, median survival was 33.9 months after CC1 surgery and 4.3 months after incomplete CC2 surgery (p = 0.005).
  • In univariate analysis of 37 biphasic patients, three factors predicted survival: Peritoneal Cancer Index (PCI, a measure of disease volume; p = 0.015; Table 2 hazard ratio 1.06 per unit, 95% CI 1.01 to 1.11), completeness of cytoreduction (p less than 0.001), and Ki-67 (p = 0.04).
  • In the biphasic group, systemic chemotherapy before surgery (p = 0.55) or after surgery (p = 0.7) was not statistically significant in predicting survival.
  • In multivariate analysis of the biphasic group, only PCI (p = 0.03) and completeness of cytoreduction (p = 0.04) remained significant.
  • CC0 surgery was achieved in 13% (2/15) of patients with PCI above 20, versus 69% (16/23) with PCI of 20 or less (p = 0.0009).
  • Table 1 lists asbestos exposure in 27 patients (19%) overall: 26 (19.6%) epithelioid and 1 (11%) biphasic. The difference was not significant. The article does not state how many patients had exposure information recorded.
• The authors' conclusion: The authors concluded that long-term survival is achievable in strictly selected biphasic patients at expert centers with low-volume disease, only after complete macroscopic cytoreduction. They concluded that CC1 resection should be regarded as incomplete for biphasic disease, and that patients with a PCI of 20 or more should not be routinely operated on. They also concluded that biphasic peritoneal mesothelioma should not be an absolute contraindication to CRS/HIPEC if complete cytoreduction can be achieved.
• Limitations the authors state:
  • The study was retrospective and multi-institutional, with selection bias, institutional learning curves and variability in treatment protocols.
  • It is unknown how many patients had an attempted but aborted CRS/HIPEC, or why.
  • The number of biphasic patients was small: 34 patients collected over 26 years from 33 centers.
  • Most biphasic cases came from three high-volume centers. This could explain the higher use of the closed HIPEC technique and the higher rate of CC0 surgery in that group.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Biphasic Mesothelioma, Peritoneal Mesothelioma, Peritoneal Surface Oncology, Epithelioid, Mesothelioma, Median Survival.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy — K.I. Votanopoulos, C. Ihemelandu, et al. (2012)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)

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