Ovarian cancer: What can we expect of second-look laparotomy?

Although the number of biopsies performed at SLL varies widely by surgeon, meticulous sampling of peritoneal surfaces may be necessary to detect occult tumor. In cases of microscopic disease, fewer than 5% of biopsies may be positive for tumor.⁷ Not surprisingly, some studies have noted a significantly worse survival rate among patients deemed to be in complete pathologic remission who underwent fewer biopsies at the time of SLL.⁸

TABLE

Components of second-look laparotomy

What do SLL findings predict?

Survival rates

Women who achieve a complete pathologic response after primary chemotherapy have the greatest survival. Rubin et al³ noted a 10-year survival rate of 51% for 91 patients after negative SLL. Median survivals for patients with negative findings have been reported in excess of 70 months.^7,9 Tuxen et al⁹ examined 242 patients after SLL and reported a median survival of 149 months for those with negative findings, versus 39 and 24 months for those with microscopic and gross disease, respectively (P.0005>

Survival rates among women with negative findings were substantially higher than among patients with positive findings, even though the latter group received salvage chemotherapy.

Recurrence rates

In a review of 38 studies encompassing 1,511 patients, Barter and Barnes⁶ noted a 23% rate of recurrence among women with negative findings at SLL. Other studies from single institutions document recurrence rates approximating 50%.^3,10 Patients experiencing recurrence after negative SLL have median survivals of 11 to 45 months.^3,8,10-12

Gross versus microscopic disease

Studies comparing outcomes based on volume of disease detected at SLL have found statistically improved survival for patients without evidence of gross tumor.^9,13-15 Podratz et al¹⁴ reported 4-year survival of 55% for women with microscopic findings versus 19% for those with gross disease (P.01>

The presence of gross tumor at SLL indicates a grave prognosis; median survival ranges between 13 and 24 months.^9,16,17 Nevertheless, several studies have shown that patients able to undergo debulking of all visible disease derive a survival benefit.^4,15,18,19

Given the potential complications of extensive debulking surgery and lack of a proven survival benefit for patients unable to achieve complete cytoreduction, debulking should only be attempted if persistent disease is judged to be completely resectable.

When SLL is positive: Salvage therapy regimens

Many different salvage regimens for epithelial ovarian cancer have been investigated for use after positive second-look laparotomy, including intraperitoneal radioactive phosphorus (³²P), systemic chemotherapy, whole abdominal radiation (WAR), hormonal therapy, and biologic response modifiers. Unfortunately, studies of salvage therapy tend to be retrospective, nonrandomized, and uncontrolled, and no proven regimen has yet been found.

Whole abdominal radiation

This modality appears to confer no definitive survival benefit and does produce toxicity. MacGibbon et al²⁰ treated 51 patients with WAR for both salvage and consolidation. Of these, 27% could not complete treatment because of progressive disease, bowel perforation, myelosuppression, and bowel toxicity. An additional 24% required treatment delays because of hematologic and gastrointestinal toxicity. Among those completing the prescribed course of radiation, 6 developed late bowel symptoms, and 2 of these required surgical intervention to relieve bowel obstruction.

Other salvage therapies

Recently, Dowdy et al¹⁸ reported long-term follow-up for 145 patients with positive findings at SLL. Neither intraperitoneal ³²P nor WAR provided a survival benefit. Multivariate analysis indicated that only grade and volume of residual disease following cytoreduction were associated with improved survival.

Other trials involving intraperitoneal interferon-alpha and carboplatin,²¹ and high-dose chemotherapy with autologous stem cell rescue²² have also failed to demonstrate any significant advantages in survival or rate of progression. An early phase II study of intraperitoneal paclitaxel showed promise: Markman et al²³ noted a complete pathologic response in 61% of patients with microscopic disease at SLL, but only 4% of those with gross disease achieved a complete response.

Need for effective consolidation therapy

A critical component of cancer care is targeting patients at highest risk of recurrence for effective consolidation therapy. The factors most strongly correlated with disease progression are stage at diagnosis, tumor grade, and volume of residual disease after initial cytoreduction.

Many consolidation therapies have been described, including systemic and intraperitoneal chemotherapy, WAR, intraperitoneal ³²P, and biologic response modifiers.

Significant risk of distant recurrences

Although most tumors recur in the abdomen and pelvis, approximately 30% recur at distant locations. For this reason, consider systemic treatment when planning the consolidation regimen. Bertucci et al²² studied systemic melphalan-based, high-dose chemotherapy with autologous stem cell rescue and noted a 5-year progression-free survival of 43% and overall survival of 75%.