Chemotherapy Before Surgery Versus Surgery First for Advanced Ovarian Cancer: A Comprehensive Patient Guide

Table of Contents

• Background: Understanding Advanced Ovarian Cancer
• How the Research Was Conducted
• Detailed Research Findings
• Survival Outcomes: Time to Death and Disease Progression
• Surgical Risks and Complications
• Quality of Life Measurements
• What These Findings Mean for Patients
• Study Limitations and Uncertainties
• Patient Recommendations and Decision-Making
• Source Information

Background: Understanding Advanced Ovarian Cancer

Epithelial ovarian cancer, which develops from the surface layer of the ovaries or the lining of the fallopian tubes, is the seventh most common cancer in women worldwide. This type accounts for approximately 90% of all ovarian cancer cases. Unfortunately, most women are diagnosed at an advanced stage when the cancer has already spread throughout the abdomen.

The disease often begins at the ends of the fallopian tubes, where individual cancer cells can break away and enter the abdominal cavity even when the primary tumor is microscopic. These cells circulate in the peritoneal fluid that lubricates the abdominal organs, eventually implanting on other surfaces and growing until they cause symptoms. The symptoms—such as bloating, abdominal discomfort, and bowel changes—are often non-specific and easily mistaken for more common benign conditions.

In Europe, only about 35% of women diagnosed with ovarian cancer survive five years after diagnosis. Conventional treatment involves two main approaches: surgery to remove as much visible cancer as possible (debulking or cytoreduction) and chemotherapy to target remaining cancer cells. Traditionally, surgery comes first followed by chemotherapy, but there has been growing interest in whether giving chemotherapy before surgery might offer benefits.

How the Research Was Conducted

This comprehensive analysis, published in the Cochrane Database of Systematic Reviews in 2019, examined all available high-quality evidence comparing two treatment approaches for advanced ovarian cancer. The researchers conducted an extensive search of medical databases up to February 2019, identifying 1,952 potential studies.

After rigorous evaluation, five randomized controlled trials met the inclusion criteria. These studies collectively involved 1,713 women with stage IIIC or IV ovarian cancer—meaning their cancer had spread extensively within the abdomen or to distant organs. The trials were conducted across multiple countries including the UK, Canada, Japan, and several European nations.

The research team compared two treatment strategies: primary debulking surgery (PDS) followed by chemotherapy versus neoadjuvant chemotherapy (NACT) followed by interval debulking surgery. All patients received platinum-based chemotherapy, which is the standard treatment for ovarian cancer. The researchers carefully analyzed data on survival, surgical complications, and quality of life outcomes.

Two reviewers independently extracted and verified all data to ensure accuracy, and they assessed each study's quality using standardized methods. The team pooled results from multiple studies where possible to provide more reliable conclusions, analyzing data from 1,521-1,631 patients for survival outcomes and 524-1,571 patients for complication rates depending on the specific measure being examined.

Detailed Research Findings

The analysis revealed crucial information about how treatment sequencing affects outcomes for women with advanced ovarian cancer. The most significant finding was that survival outcomes were remarkably similar between the two approaches, but complication rates differed substantially.

For overall survival—the length of time from treatment until death from any cause—the hazard ratio was 1.06 with a 95% confidence interval of 0.94 to 1.19. This statistical measure indicates that there was no meaningful difference in survival between starting with chemotherapy versus starting with surgery. The consistency across studies was high (I² = 0%), meaning all studies pointed in the same direction.

Similarly, for progression-free survival—the length of time until the cancer progresses or worsens—the hazard ratio was 1.02 with a 95% confidence interval of 0.92 to 1.13. Again, this shows no significant difference between the two treatment sequences. The evidence for both survival outcomes was rated as moderate certainty, meaning we can be reasonably confident in these results.

Where the treatments differed markedly was in surgical complication rates. Women who received chemotherapy before surgery experienced substantially fewer serious adverse events related to their operations. These differences were statistically significant and clinically meaningful for several specific complications.

Survival Outcomes: Time to Death and Disease Progression

The comprehensive analysis of survival data provides reassurance that neither treatment approach compromises life expectancy. The pooled data from three studies involving 1,521 women showed virtually identical overall survival between the two groups. The hazard ratio of 1.06 indicates that, if anything, there might be a very slight advantage to primary debulking surgery, but the confidence interval crossing 1.0 means this difference is not statistically significant.

Similarly, progression-free survival data from four studies including 1,631 women demonstrated a hazard ratio of 1.02, essentially indicating no difference in how quickly the cancer progressed between the two treatment approaches. The consistency across studies (I² = 0% for both outcomes) strengthens our confidence in these findings.

These results are particularly important because they come from randomized controlled trials, the gold standard in medical research. The studies included women with advanced disease (stage IIIC/IV), and a large proportion had very bulky tumors, making these findings especially relevant for patients with extensive disease.

The moderate certainty rating for these survival outcomes means that while further research might refine our understanding, it's unlikely to fundamentally change the conclusion that both treatment sequences offer similar survival benefits.

Surgical Risks and Complications

The most striking differences between the two treatment approaches emerged in surgical complication rates. Women who received chemotherapy before surgery experienced significantly fewer serious adverse events, with particularly notable reductions in several specific complications:

• Need for blood transfusion: Risk ratio 0.80 (95% CI 0.64 to 0.99) based on 1,085 women from four studies—representing a 20% reduction in transfusion needs
• Venous thromboembolism: Risk ratio 0.28 (95% CI 0.09 to 0.90) based on 1,490 women from four studies—a 72% reduction in dangerous blood clots
• Serious infections: Risk ratio 0.30 (95% CI 0.16 to 0.56) based on 1,490 women from four studies—a 70% reduction in major infections
• Stoma formation: Risk ratio 0.43 (95% CI 0.26 to 0.72) based on 581 women from two studies—a 57% reduction in needing an intestinal stoma
• Bowel resection: Risk ratio 0.49 (95% CI 0.26 to 0.92) based on 1,213 women from three studies—a 51% reduction in needing bowel removal
• Postoperative mortality: Risk ratio 0.18 (95% CI 0.06 to 0.54) based on 1,571 women from five studies—an 82% reduction in death within 30 days of surgery

The evidence quality for these surgical outcomes varied from low to moderate certainty, with the strongest evidence (moderate certainty) supporting the reductions in infections, stoma formation, bowel resection, and postoperative mortality.

Quality of Life Measurements

Quality of life data were less consistently reported across the studies, and the results were more difficult to interpret. Researchers used standardized quality of life instruments including the EORTC QLQ-C30 and QLQ-Ov28 questionnaires, which measure various aspects of physical, emotional, and social functioning.

Two studies involving 307 participants showed a slight difference in quality of life scores at six months (mean difference -1.34, 95% CI -2.36 to -0.32), but the clinical significance of this small difference is uncertain. Another study with 217 participants using different measurement approaches found a mean difference of 7.60 (95% CI 1.89 to 13.31), suggesting possibly better quality of life with neoadjuvant chemotherapy.

Overall, the evidence for quality of life outcomes was rated as very low certainty due to inconsistencies between studies, heterogeneity in measurement approaches, and high rates of missing data. This means we cannot draw firm conclusions about how treatment sequencing affects quality of life, and this remains an important area for future research.

What These Findings Mean for Patients

This comprehensive analysis provides important evidence that can inform treatment decisions for women with advanced ovarian cancer. The most significant finding is that starting with chemotherapy does not compromise survival outcomes compared to starting with surgery. This is crucial information because it means patients and doctors can choose the sequence that best fits an individual's circumstances without worrying about sacrificing survival time.

The reduced surgical complication rates with neoadjuvant chemotherapy are particularly important for women who might be less able to tolerate extensive surgery due to age, overall health status, or particularly extensive disease. The 82% reduction in postoperative mortality is especially noteworthy, as is the approximately 50% reduction in needing bowel resection or stoma formation.

These findings support a more personalized approach to ovarian cancer treatment. Rather than a one-size-fits-all protocol, doctors can now recommend treatment sequencing based on individual factors including surgical resectability (how completely the cancer can be removed), age, specific cancer characteristics, overall health status, and patient preferences.

For women with very bulky disease or significant health concerns, starting with chemotherapy may offer meaningful advantages in reducing surgical risks and complications while providing equivalent survival outcomes. The research team noted that they are awaiting results from additional ongoing studies that may provide further guidance in this area.

Study Limitations and Uncertainties

While this analysis provides valuable insights, it's important to understand its limitations. The evidence quality varied across different outcomes, with survival data rated as moderate certainty but some surgical complication data rated as low certainty due to concerns about how completely outcomes were reported.

The quality of life measurements were particularly problematic, with very low certainty evidence due to inconsistencies between studies and high rates of missing data. This means we cannot confidently determine how treatment sequencing affects patients' daily lives and well-being beyond survival and surgical complications.

All included studies focused on women with stage IIIC/IV disease—those with the most advanced ovarian cancer—so these findings may not apply to women with earlier stage disease. Additionally, a large proportion of participants had very bulky tumors, which means the results might be most relevant for patients with extensive disease.

The researchers identified two ongoing studies and one unpublished study that were not included in this analysis. As these results become available, they may provide additional insights or modify our understanding of the optimal treatment sequence for advanced ovarian cancer.

Patient Recommendations and Decision-Making

Based on this comprehensive evidence, women with advanced ovarian cancer and their healthcare providers should consider several factors when deciding on treatment sequencing:

1. Discuss both options thoroughly with your medical team, understanding that survival outcomes are similar with either approach
2. Consider your individual surgical risks—if you have factors that increase surgical risk (age, other health conditions, very extensive disease), neoadjuvant chemotherapy may significantly reduce complications
3. Evaluate the importance of avoiding specific complications—if avoiding bowel resection, stoma formation, or blood transfusions is particularly important to you, neoadjuvant chemotherapy offers substantial advantages
4. Consider practical aspects—starting with chemotherapy may allow time to prepare physically and emotionally for major surgery
5. Ask about center expertise—the ability to achieve optimal surgical outcomes may vary between treatment centers

Ultimately, the decision should be individualized based on your specific cancer characteristics, overall health, personal values, and preferences. This research provides reassurance that neither approach compromises survival, allowing you to make a decision based on which risks and benefits matter most to you personally.

Source Information

Original Article Title: Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer

Authors: Coleridge SL, Bryant A, Lyons TJ, Goodall RJ, Kehoe S, Morrison J

Publication Details: Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD005343. DOI: 10.1002/14651858.CD005343.pub4

Note: This patient-friendly article is based on peer-reviewed research from the Cochrane Collaboration, an international organization that provides systematic reviews of healthcare interventions.