Eliminating tumor cell entrapment from the natural history of ovarian cancer, a narrative summary

Objective: The surgery performed on patients with abdominal or pelvic malignancy has a profound effect on the natural history of that disease process. In this manuscript we examine the impact of hysterectomy performed in patients with ovarian cancer. Methods: Two assessment tools were reviewed to quantitate the changes induced by hysterectomy on the patterns of recurrence. The prior surgical score (PSS) correlates the survival of patients with the extent of surgery that was performed prior to cytoreductive surgery (CRS). Also, an assessment of anatomic sites of disease documented at the time of CRS for recurrent ovarian cancer determined the extent of tumor cell entrapment (TCE) at sites of surgical trauma. Results: Patients with recurrence of ovarian malignancy who had a CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) showed a statistically significant reduced survival if they had a high PSS. The data from TCE assessment showed that the sites of surgical trauma that occurred with hysterectomy performed for treatment of the primary ovarian cancer was associated with disease within the abdominal incision, laparoscopy port sites, and the resection site for hysterectomy. Conclusions: Hysterectomy performed in patients with stage 3 ovarian malignancy who have large numbers of free cancer cells within the abdominal and pelvic space had a profound effect upon the natural history of this malignancy as determined by PSS and an assessment of anatomic sites of TCE. HIPEC was suggested as a treatment to reduce the reimplantation of cancer cells at sites of surgical trauma following hysterectomy.

Cytoreductive surgery; Hysterectomy; Cisplatin; Paclitaxel; HIPEC; EPIC; Prior surgical score; Peritoneal metastases; Regional chemotherapy

[1] Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. International Journal of Women’s Health. 2019; 11: 287–299.

[2] Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Seminars in Surgical Oncology. 2000; 19: 3–10.

[3] Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018; 68: 284–296.

[4] Kuhn E, Kurman RJ, Vang R, Sehdev AS, Han G, Soslow R, et al. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma-evidence supporting the clonal relationship of the two lesions. Journal of Pathology. 2012; 226: 421–426.

[5] Sehouli J, Senyuva F, Fotopoulou C, Neumann U, Denkert C, Werner L, et al. Intra-abdominal tumor dissemination pattern and surgical outcome in 214 patients with primary ovarian cancer. Journal of Surgical Oncology. 2009; 99: 424–427.

[6] Lengyel E. Ovarian cancer development and metastasis. American Journal of Pathology. 2010; 177: 1053–1064.

[7] Sugarbaker PH. Peritoneum and peritoneal cavity. In Standring S (ed.) Gray’s Anatomy (pp. 1098–1110). 41st edn. Chennai, India: Churchill Livingston/Elsevier. 2015.

[8] Carmignani CP, Sugarbaker TA, Bromley CM, Sugarbaker PH. Intraperitoneal cancer dissemination: mechanisms of the patterns of spread. Cancer Metastasis Reviews. 2003; 22: 465–472.

[9] Goldstein P, Cabanas J, da Silva R, Sugarbaker PH. Management of peritoneal surface malignancy, a review. Cancer Therapy 2005; 3: 299–320.

[10] Weiss L. Some effects of mechanical trauma on the development of primary cancers and their metastases. Journal of Forensic Sciences. 1990; 35: 614–627.

[11] Sethna KS, Sugarbaker PH. New prospects for the control of peritoneal surface dissemination of gastric cancer using perioperative intraperitoneal chemotherapy. Cancer Therapy. 2004; 2: 79–84.

[12] Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy. 2020; 5: 28.

[13] Eggermont AM, Steller EP, Marquet RL, Jeekel J, Sugarbaker PH. Local regional promotion of tumor growth after abdominal surgery is dominant over immunotherapy with interleukin-2 and lymphokine activated killer cells. Cancer Detection and Prevention. 1988; 12: 421–429.

[14] Ceelen W, Pattyn P, Mareel M. Surgery, wound healing, and metastasis: recent insights and clinical implications. Critical Reviews in Oncology/Hematology. 2014; 89: 16–26.

[15] Jacquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. Journal of Experimental & Clinical Cancer Research. 1996; 15: 49–58.

[16] Look M, Chang D, Sugarbaker PH. Long-term results of cytore-ductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. International Journal of Gynecological Cancer. 2004; 14: 35–41.

[17] Sugarbaker PH. Patterns of recurrence in women with ovarian cancer having hysterectomy for treatment of primary disease.(Submitted)

[18] van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. New England Journal of Medicine. 2018; 378: 230–240.

[19] Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, et al. Cytoreductive Surgery and HIPEC in Recurrent Epithelial Ovarian Cancer: a Prospective Randomized Phase III Study. Annals of Surgical Oncology. 2015; 22: 1570–1575.

[20] Chitrathara K, Sheikh ZA, Vijaykumar DK, Kuriakose S, Anupama R, Nandeesh M. Is hysterectomy needed in ovarian cancer?Indian Journal of Cancer. 2011; 48: 471–476.

[21] Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas—a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecologic Oncology. 2001; 83: 355–362.

[22] Dizon DS, Birrer MJ. Making a Difference: Distinguishing Two Primaries from Metastasis in Synchronous Tumors of the Ovary and Uterus. Journal of the National Cancer Institute. 2016; 108: djv442.

[23] Bunting MW, Jaaback KS, McNally OM. Routine Hysterectomy in the Surgical Management of Ovarian Cancer: a Retrospective Case Series, Physician Opinion Survey, and Review of the Literature. International Journal of Gynecologic Cancer. 2011; 21: 1579–1584.