Pegulicianine: a game changer for image-guided breast cancer surgery

Dear Editor, Breast cancer remains a formidable challenge worldwide, with an estimated 2.3 million new cases and 670 000 deaths in 20221. Traditional lumpectomy involves the removal of cancerous tissue while sparing as much of the breast as possible2. However, achieving clean margins—ensuring no cancer cells are left behind—has always been somewhat of a surgical gamble2. Residual disease often necessitates additional surgeries, increasing patient distress, and healthcare costs2,3. The recent approval of pegulicianine (Lumisight) by the U. S. Food and drug administration on 17 April 2024, an innovative imaging drug in enhancing the precision and efficacy of cancer resections, represents a transformative advancement in the realm of breast cancer surgery4. Pegulicianine is a fluorescent imaging drug administered intravenously before surgery, used in conjunction with the Lumicell Direct Visualization System (DVS) or other approved devices following standard of care (SOC) lumpectomy4. This combination allows surgeons to visualize cancerous tissues that may not be detectable by the human eye or traditional imaging techniques during surgery. One of the primary benefits of pegulicianine is its potential to enhance surgical precision. The drug’s ability to fluoresce in the presence of cancer cells provides real-time, intraoperative guidance that helps surgeons identify and remove additional cancerous tissues at the initial surgery. This capability is crucial, particularly in cases where cancerous tissues are not palpable or visually distinct from normal tissues. A recent multicenter clinical trial (NCT03686215), utilized Lumicell DVS following SOC lumpectomy in 357 patients, and evaluated the fraction of participants in which residual tumor tissue was detected and resected5. Pegulicianine use led to additional resections in 7.6% of cases, which might have been missed without the aid of this imaging technology. Such advancements could significantly reduce the need for re-excision surgeries, which currently occur in up to 20% of breast cancer lumpectomy cases2,4. While the introduction of pegulicianine into surgical practice is promising, its efficacy is balanced by a sensitivity of 49.1% and specificity of 86.5%4,5. These figures suggest that while the drug is highly specific in identifying cancer-free regions, its sensitivity in detecting all cancerous areas is moderate. Therefore, pegulicianine should be viewed as an adjunct to, rather than a replacement for, standard surgical judgment and other imaging modalities. Furthermore, 43% of patients experienced at least one false positive image, and 8% had at least one false negative image4,5. These statistics highlight the potential risks of both over-resection due to false positives, which could lead to unnecessary tissue loss, and under-resection due to false negatives, potentially leaving behind residual disease. The safety profile of pegulicianine is also a critical consideration. The most significant adverse reaction is hypersensitivity, including anaphylaxis, although this is relatively rare (1.4% with 0.6% being anaphylactic reactions)4,5. Nevertheless, it underscores the necessity for thorough preoperative screening for hypersensitivity to contrast media or polyethylene glycol (PEG), meticulous intraoperative monitoring, and the readiness of emergency resuscitation measures. Another common side effect, experienced by 85% of patients, is chromaturia—an abnormal urine color—which is generally benign and self-limiting but must be communicated to patients to avoid undue alarm4,5. As we integrate pegulicianine and Lumicell DVS into clinical practice, ongoing evaluation through postmarket surveillance and further research will be pivotal. These studies should aim to refine the use cases for pegulicianine, optimize its dosage and administration protocols, and evaluate long-term outcomes in diverse patient populations. Moreover, the economic implications of adopting this technology must be considered. While the upfront costs of pegulicianine and the necessary imaging systems may be high, the potential reduction in re-excision surgeries and the associated healthcare expenditures could justify these initial investments. In conclusion, pegulicianine heralds a new era in the surgical management of breast cancer, offering surgeons an unprecedented ability to identify and resect cancerous tissues with greater accuracy during lumpectomies. By potentially reducing the frequency of re-excisions and improving surgical outcomes, pegulicianine could indeed be a game-changer in the fight against breast cancer. As with any new technology, its integration into routine clinical practice must be approached with an evidence-based strategy, balancing its benefits against its limitations and costs. Ethical approval Not applicable. Consent Not applicable. Sources of funding Not applicable. Author contribution A.A.: conceptualization, project administration, supervision, validation, writing – original draft, and writing – review and editing; P.S., R.K.S., D.S., M.A., M.N.K., S.G., Q.S.Z., and S.R: supervision, validation, and writing – review and editing. Conflicts of interest disclosure The authors declare that they have no conflicts of interest. Research registration unique identifying number (UIN) Name of the registry: not applicable. Unique identifying number or registration ID: not applicable. Hyperlink to your specific registration (must be publicly accessible and will be checked): not applicable. Guarantor Ayush Anand. Data availability statement Not applicable. Provenance and peer review Not commissioned, externally peer-reviewed. Assistance with the study Not applicable.

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