The aim of this study was to assess the feasibility of laser treatment for intraductal papillomas causing PND. This interventional study demonstrated that intraductal laser ablation during ductoscopy was technically feasible in patients with intraductal lesions. The Thulium laser was capable of evaporating intraductal papillary lesions in cases with remaining lesions after biopsy resulting in discontinuation of PND complaints in 77.8% after treatment in the follow-up period of three months. There were no complications, and only 1 patient complained of post-procedural nipple pain, which can also generally be seen after ductoscopy so this cannot with certainty be attributed to the laser ablation. Laser ductoscopy thereby has potential to safely improve the therapeutic intervention capability of ductoscopy in patients with benign intraductal lesions and successfully prevent unnecessary exploratory surgery. However, further refinement and validation in follow-up clinical trials are necessary.

Ductoscopy enables the detection of malignancies with a specificity of 92% and a sensitivity of 58% [26]. Although current intraductal biopsy tools can remove lesions during ductoscopy, their removal often remains incomplete. [16, 27]. According to a prior study conducted by our research team, removal of the lesion was possible in only 36.8% of the study population [14]. In these cases, in which tissue sampling from the lesion can be obtained, laser ablation serves as a promising addition to the therapeutic capabilities of ductoscopy while retaining histological confirmation. In the present study, laser ductoscopy made it possible to remove intraductal lesions in 77.8% of patients with remaining intraductal lesions after basket removal. After undergoing regular ductoscopy, patients can still suffer from PND and therefore undergo a surgical procedure or a second ductoscopy [16,17,18]. According to a cohort study, persistent or recurrent PND after a first ductoscopy procedure was primarily caused by a remaining intraductal papilloma in the majority of patients (95%) [19]. In such cases, if laser ductoscopy was performed during the primary ductoscopy procedure, complete removal of the intraductal lesion may have been possible in a greater number of patients, thereby potentially avoiding a second (surgical) intervention.

Laser ductoscopy can improve the patient selection process for surgical procedures in the workup of PND without clinical or radiological abnormalities, because successful (laser) sablation prevents the necessity for further invasive procedures [14]. However the presence of an intraductal mass is a possible predictor for malignancy, so definitive histological diagnosis is mandatory before performing laser ablation [15]. Consequently, laser ductoscopy can lead to a reduction of the need for additional surgery and fewer surgery-related complications such as hematomas, surgical site infections, and seromas [8].

However, the role of laser ductoscopy in cases of PND caused by intraductal DCIS or invasive cancer is uncertain. In this study, one patient experienced PND due to an intraductal papilloma with a focus of ADH/DCIS grade 1. Following an intraductal biopsy during ductoscopy, laser ductoscopy was performed. Post-procedure, the localization of the tumor site for surgical resection by wide local excision was not possible because there was no remaining lesion on imaging due to complete removal with laser ablation. In this case, follow-up with mammography will be carried out. Given that observation for low-grade DCIS is becoming more common and the natural progression of ADH or DCIS within a papilloma is not well known, this may be an acceptable risk when paired with clinical and imaging surveillance. The potential for laser ductoscopy to become a routine intervention for premalignant breast lesions remains speculative. Ongoing clinical trials, such as LORD, LORIS, COMET, and LORETTA, are investigating whether low-risk DCIS is overtreated and if active monitoring is a safe approach [28]. Preliminary results suggest that active surveillance for low-risk DCIS is feasible. This supports the possibility that follow-up after laser ablation of low-grade DCIS within a papilloma may be safe. However, long-term outcomes are awaited.

According to our findings, laser ductoscopy can be safely integrated into the diagnostic and therapeutical approach for pathological nipple discharge to remove intraductal lesions in patients with remaining intraductal lesions after basket removal and subsequent histological biopsy. This procedure can be incorporated into the initial ductoscopy procedure in the presence of a visible residual lesion. Additionally, it can also be performed during a second ductoscopy procedure in patients with recurrence of complaints due to a remaining lesion. Laser ductoscopy can be implemented in medical centers already performing ductoscopy procedures for pathological nipple discharge. The widespread adoption of this technique into the work-up of PND, particularly in centers performing duct excision surgery, holds promise for the future.

To our knowledge, this is the first study to report on the application of intraductal laser ablation within a ductoscopy procedure. However, certain limitations do warrant consideration. Given the design of this study as a feasibility study, it features a relatively small sample group size of included patients. This study clearly showed the feasibility of intraductal laser ablation during ductoscopy using a Thulium laser. Nevertheless, to comprehensively evaluate both diagnostic accuracy and therapeutic efficacy, further refinement and validation in clinical trials are necessary. Additionally, the identification of optimal power settings for achieving adequate removal, as well as an examination of the effects of using different types of lasers (e.g., Holmium vs. Thulium laser) on intraductal papillomas, will have to be studied [29, 30]. Moreover, differentiation between ADH and low-grade DCIS is based on size criterion of 3 mm in papillary lesions. Therefore, due to the small size of the biopted tissue, definitive categorization may not always be possible.

To conclude, laser ablation during ductoscopy is safe and feasible in for evaporating residual intraductal breast lesions. This technique holds the potential to enhance the minimally invasive therapeutic intervention capabilities of ductoscopy procedures for patients suffering from PND without other clinical or radiological abnormalities.