At a recent international academic conference, Professor Walter Weber from University Hospital Basel, Switzerland, detailed the results of the international randomized Phase III PREPEC trial (OPBC-02). The study aimed to compare the impact of two implant placement strategies—Prepectoral versus traditional Subpectoral—on the quality of life and safety of patients undergoing implant-based breast reconstruction (IBBR) following therapeutic or prophylactic mastectomy.01 Background and Study Rationale: The Trade-off Between Surgical De-escalation and Quality of Life
Mastectomy is the primary treatment for approximately 40% of breast cancer patients and some high-risk individuals (prophylactic mastectomy). About half of these patients choose immediate breast reconstruction, and implant-based breast reconstruction (IBBR) is currently the most widely used technique in clinical practice. Traditional IBBR typically employs a “subpectoral placement” approach, which requires detaching the pectoralis major muscle from the chest wall and squeezing the implant beneath the muscle. The goal is to provide increased soft tissue coverage through muscle protection, thereby reducing the risk of skin complications. However, this cutting and stripping of the muscle often leads to long-term postoperative pain, chest tightness, weakness, and even animation deformity. Professor Walter Weber pointed out that with advancements in soft tissue coverage techniques and auxiliary materials (such as biological matrices and synthetic meshes), a clinical trend toward “prepectoral placement” has emerged. This involves preserving the pectoralis major and placing the implant directly beneath the skin flap. Whether this “surgical de-escalation” approach can improve postoperative quality of life by reducing muscle damage without increasing the risk of serious complications is the core question explored by the PREPEC study.
02 Study Design: A Pragmatic Exploration of Global Multicenter Real-World Authenticity
The PREPEC trial (OPBC-02) is an international, multicenter, randomized, controlled, Phase III clinical trial. Its research design is highly pragmatic, meaning interventions were conducted while adhering as closely as possible to routine clinical care. • Subject Population: Included a broad population of patients planned for IBBR following therapeutic or prophylactic mastectomy. Exclusion criteria were minimal, only excluding cases where the surgeon deemed the skin flap unsuitable for prepectoral placement or cases transitioning from temporary expanders to autologous reconstruction. • Sample Size and Grouping: The study randomized 383 patients across 26 centers in 10 countries, with a final effective sample size of 372 patients. Patients were allocated 1:1 to either the prepectoral group or the subpectoral group. • Treatment Details: The study did not mandate uniform surgical technical details but rather recorded high clinical heterogeneity. For example: 50% of cases used synthetic or biological mesh, 75% were single-stage reconstructions, 25% received radiotherapy, and 42% received chemotherapy. • Evaluation Indicators: o Primary Endpoint: Patient-reported “Physical well-being of the chest” at 2 years post-surgery, assessed using the Breast-Q scale. The Minimal Clinically Important Difference (MID) was set at 4 points (later updated to 3 points based on the latest literature). o Key Secondary Safety Endpoint: Rate of implant/expander loss within 2 years. A non-inferiority margin of 5% was set. o Other Indicators: Complications (animation deformity, capsular contracture), psychological health, sexual satisfaction, etc.
03 Primary Endpoint Analysis: Prepectoral Placement Significantly Improves Physical Well-being
Study results showed that during the 2-year long-term follow-up, the prepectoral group demonstrated a significant advantage in Breast-Q “Physical well-being of the chest” scores. • Data Results: The difference in scores between the prepectoral and subpectoral groups was 4.8 points, which is not only statistically significant (P-value showed significant difference) but also exceeded the preset MID of 4 points. • Symptom Improvement: The improvement in scores primarily reflected a significant reduction in patient-reported muscle pain, chest tightness, tenderness, and difficulty lifting upper limbs. • Subgroup Consistency: Whether the surgery was unilateral or bilateral, whether mesh was used, whether radiotherapy was received, or whether single/two-stage reconstruction was performed, the physical well-being benefits of the prepectoral group remained highly consistent. Professor Walter Weber emphasized that “less surgery” indeed brings about an improvement in Quality of Life (QoL), and this finding provides strong evidence in support of surgical de-escalation.
04 Safety and Complications: The Cost of Implant Loss Risk vs. Long-term Aesthetic Benefits
Although the prepectoral group won decisively in terms of quality of life, analysis of safety data revealed challenges with this approach. • Implant Loss Rate: The implant loss rate in the prepectoral group was 21%, compared to 14.5% in the subpectoral group. The absolute difference between the two groups was 5.7%, exceeding the pre-specified 5% non-inferiority margin. This means that for every 20 patients undergoing prepectoral reconstruction, there is one additional case of implant loss. • Early Complications: In the perioperative period, more early complications were observed in the prepectoral group, with a difference between groups of 2.5% to 5%, which is related to the pressure of the implant directly loading onto the skin flap. • Long-term Aesthetic Complications: However, in terms of long-term complications, the prepectoral group showed a clear advantage. The incidence rates of animation deformity and capsular contracture were significantly lower than in the subpectoral group. This indicates that preserving the integrity of the pectoralis major not only avoids implant displacement caused by muscle movement but may also alter the microenvironment of capsule formation to some extent.
05 Psychosocial Dimensions: A Trend of All-around Benefits
In addition to the primary endpoint, the PREPEC study also used the Breast-Q scale to examine patients’ psychological health, sexual health, and overall satisfaction with their breasts. Data indicated that the prepectoral group showed comprehensive improvements in Psychosocial well-being, Sexual well-being, and overall Satisfaction with breasts, with differences between groups all reaching the MID requirement of 4 points or more. This proves that physical recovery brought about by reducing surgical trauma can translate into a comprehensive return of psychological and social functions for patients.
06 Conclusion and Outlook: Moving Toward Individualized Precision Decision-making
Professor Walter Weber summarized the PREPEC trial:
- Pragmatic Evidence: The PREPEC study, through its pragmatic design, confirmed that in real-world clinical practice, prepectoral positioning can significantly improve the physical well-being and multi-dimensional quality of life for IBBR patients.
- Risk Balance: This QoL benefit comes at the cost of a higher risk of implant loss (an additional risk of approximately 5.7%). This is a tough trade-off in clinical decision-making; for that 1 in 20 patients, it is a serious negative event.
- Clinical Recommendations: Given the significant advantages of prepectoral placement in reducing animation deformity and capsular contracture and improving QoL, this technique should be considered one of the standard treatment options for breast reconstruction. However, doctors must conduct in-depth risk disclosure with patients preoperatively, weighing the improvement in quality of life against the potential risk of implant loss.
[Expert Commentary]
The PREPEC study provides high-quality evidence-based medical proof for the choice of post-mastectomy reconstruction techniques. It clarifies the direction of “surgical de-escalation”—the value of preserving pectoralis major function. Future research should further explore how to reduce the risk of perioperative loss while maintaining the benefits of prepectoral placement through optimized patient screening (e.g., identifying high-risk skin flaps), refined surgical techniques, or improved auxiliary materials, thereby truly achieving precise and individualized reconstruction decisions.
