Systematic review and meta-analysis on safety and effectiveness of postoperative radiotherapy after ear keloid excision

INTRODUCTION

Keloids are a challenging fibroproliferative scar disorder with high recurrence rates despite treatment. They are abnormal fibroproliferative scars that develop after surgery, injury, or minor skin irritation. While some external stimuli can evoke the development of keloids, there are patients with genetic predispositions to developing keloids, and in some instances, keloids may also occur spontaneously without an identifiable trigger^[1,2].

A range of therapeutic strategies has been investigated to manage keloids, including topical treatments such as corticosteroid injections, intralesional chemotherapy, cryotherapy, and laser therapy^[3]. Nevertheless, surgical excision remains the primary treatment approach, particularly for primary auricular keloids. Although surgical excision may be successful in excising lesions, recurrence rates remain high and are often reported to exceed 50%. Surgical method choice is critical in reducing rates of recurrence and preserving morphology of the ear. Complete excision is largely favored for minor auricular keloids; nevertheless, application in larger keloids is restricted by increased wound tension and risk of distortion of auricular structure. Core excision (i.e., removal of the fibrotic core while preserving the overlying epidermis and papillary dermis) may reduce contour deformity risk^[4]. For the management of earlobe keloids, excision with primary closure is generally successful, although for simple direct linear closure of helical keloids it is generally not feasible or results in severe deformity of ear shape^[5]. In such cases, reconstruction through the application of flaps has helped to redistribute stress at the periphery of the wound and consequently diminish the risk of recurrence^[6].

Postoperative radiotherapy has emerged as a valuable adjunct to surgical excision in the treatment of keloids^[7]. Radiotherapy alone is associated with high recurrence; however, adjuvant radiotherapy after excision has been associated with improved outcomes^[8]. Reported efficacy rates for this combined approach range from 28% to 98%; however, the variability in results reflects a lack of standardized treatment protocols in prior studies. Numerous studies have evaluated the effectiveness of combined treatment modalities, of which results from some studies reflect superb success and limited recurrence rates, thus suggesting its effectiveness as a treatment approach^[9].

The aim of this systematic review is to analyze the efficacy and safety of postoperative radiotherapy plus surgical excision, with/without reconstruction by flap, for the treatment of ear keloids. Specifically, this review assesses the effects of these treatment modalities on recurrence rates and late clinical outcomes and provides a combined analysis of their clinical value.

METHODS

The systematic review adheres to the guidelines established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)^[10]. The protocol for this systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), under the registration number CRD420251015501.

RESULTS

Search results and included studies

A comprehensive literature search was conducted across four electronic databases, PubMed, ScienceDirect, Cochrane, and EBSCOHost, using the keywords “ear keloid” or “auricular keloid” combined with “radiotherapy”, “radiation therapy”, or “postoperative radiotherapy”, and “excision”. The literature search was confined to publications in the English language and was restricted to studies published between January 2015 and August 2025. This search yielded 45 articles in PubMed, 286 articles in ScienceDirect, 1 article in Cochrane, and 13 articles in EBSCOHost. A total of 345 articles were identified through the initial database search. Following the removal of duplicates, 314 articles underwent title and abstract screening. Of these, 19 articles were assessed for full-text eligibility, and ultimately, 14 studies were included in this systematic review and meta-analysis. The study designs varied, comprising one randomized controlled trial (RCT), three case series, and multiple cohort studies. Figure 1 illustrates the progression of the literature search process.

Figure 1. PRISMA flowchart of the literature search. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Outcomes: recurrence rate

Two proportional meta-analyses [Figures 2 and 3] summarized pooled recurrence proportions for studies reporting excision with postoperative radiotherapy and studies reporting excision with flap reconstruction plus postoperative radiotherapy. The pooled recurrence proportion was 0.200 (95%CI: 0.052-0.348) for excision plus radiotherapy and 0.078 (95%CI: 0.000-0.160) for flap plus radiotherapy, both under random-effects models. Between-study heterogeneity was substantial in both analyses (I² = 90% and 72%, respectively). Funnel plot inspection suggested asymmetry, particularly for the excision plus radiotherapy group [Figure 4].

Figure 2. Proportional meta-analysis of recurrence rates following excision in conjunction with postoperative radiotherapy for the management of ear keloids^[9,15-22].

Figure 3. Proportional meta-analysis of recurrence rates following excision with flap in conjunction with postoperative radiotherapy for the management of ear keloids^[6,7,23-25].

Figure 4. The funnel plot illustrates the standard error in relation to the proportion for studies evaluating excision interventions (left) and flap interventions (right).

As an additional descriptive summary, crude recurrence proportions were calculated across studies with extractable numerators and denominators. For electron-beam radiotherapy, 38 recurrences/553 keloids (6.9%) were reported; for non-electron modalities, 27/203 (13.3%). When grouped by total prescribed dose, regimens ≥ 15 gray (Gy) reported 15/426 (3.5%), whereas regimens < 15 Gy reported 25/73 (34.2%); other dose groupings were heterogeneous (2/28, 7.1%) or unclear/not reported (23/229, 10.0%). When grouped by reported timing of initiation, radiotherapy started ≤ 24 h reported 38/225 (16.9%), 24-72 h reported 3/65 (4.6%), > 72 h reported 3/239 (1.3%), and unclear/unreported timing reported 21/227 (9.3%).

Safety outcomes: complications or side effects

Postoperative adverse effects and complications are summarized in Figure 5. Overall, reported events were relatively infrequent and generally mild across the included studies, suggesting that the interventions were well tolerated in most series. Acute radiotherapy-related effects were most commonly limited to transient skin reactions, including mild erythema and redness, which were typically self-limiting and did not require additional intervention. Late non-malignant complications were variably reported and primarily included skin hyperpigmentation and hypertrophic scarring. These events were more frequently described in excision-based series. In flap-based reports, flap-related complications were uncommon, with a single case of postoperative flap congestion documented. Reporting of long-term and oncologic outcomes was limited. One cohort study described a case of lung carcinoma during follow-up, while most other studies did not systematically report malignancy-related outcomes or were not designed to detect rare late events.

Figure 5. Reported side effects and complications following excision in conjunction with postoperative radiotherapy for the management of ear keloids.

DISCUSSION

Keloids are defined as raised scars that extend beyond the margin of the original wound, often arising from minor tissue injuries or a genetic predisposition. Histologically, keloids are marked by an excessive aggregation of fibroblasts and type I collagen in the inflammatory reticular dermis. As a result, the balance between collagen deposition and collagen lysis, which is essential in normal wound healing, is not achieved^[26]. In their review on the epidemiology of keloids, Huang et al. reported that the average incidence is estimated to be 5%-10% among individuals of African populations, 0%-0.1% in Asian populations, and less than 0.1% in other regions^[27].

Keloids can develop on any part of the body, with the most commonly affected areas including the anterior chest, earlobes, upper chest, and cheeks. In contrast, they are rarely found on the eyelids, cornea, palms, mucous membranes, genitalia, and soles^[28]. Bayat et al. reported that 42.2% of patients had keloids in multiple anatomical locations, with the earlobe being the most commonly affected site, accounting for 24% of cases. Ear piercing was the most frequent triggering factor, and earlobe keloids typically appeared at an average age of 17.1 years. Ear keloids often cause significant stress for patients due to their visible cosmetic impact, and pose challenges for surgeons because of the complexity of treatment and high risk of recurrence^[29].

Management of ear keloids typically involves a combination of nonsurgical and surgical modalities. Various methodologies have been utilized to treat ear keloids, such as surgical excision, intralesional corticosteroids, use of radiotherapy, laser, cryotherapy, or combination therapies. Injection of intralesional corticosteroids is usually utilized for small-sized ear keloids, while large keloids can be surgically excised. If the keloid has a narrow pedicle, complete excision with primary closure can usually be performed. If, however, the stalk is broader, then a conservative approach is advised, with the goal of reducing scar bulk rather than achieving complete excision. Excising large auricular keloids with wide bases can produce large defects that cannot be primarily closed. Tensioning the wound edges can deform the ear. When primary closure cannot be performed and there is a risk of ear deformity due to improper closure, reconstruction with flaps can be utilized. Anatomical subsite within the auricle may act as an important effect modifier in surgical planning and outcomes. Earlobe keloids may often be managed with wedge excision and primary closure, whereas keloids involving cartilaginous auricular subunits (such as the helix or scapha) more frequently require local flap reconstruction to prevent contour deformity and excessive wound tension^[7,30,31]. Types of flaps that can be utilized to reconstruct the ear for keloids include tongue flap, fillet flap, cross flap, and keystone flap^[32].

Surgical excision alone has been reported to have a high recurrence rate, ranging from 45% to 100%^[33]. To reduce this risk, adjuvant radiotherapy may be considered as part of postoperative management. First described by De Beurmann and Gougerot in 1906, radiotherapy has since been widely used as an adjunct to surgical excision. It has demonstrated a success rate of 67% to 98%, with recurrence rates below 10%, significantly lower than excision alone^[34]. Postoperative radiotherapy has been established as one of the most effective strategies for preventing keloid recurrence after surgical excision. Its mechanism involves the suppression of fibroblast proliferation, neovascularization, and inflammatory mediators, key elements responsible for the abnormal wound healing characteristic of keloids. Ionizing radiation inhibits the expression of growth factors such as transforming growth factor beta (TGF-β) and platelet-derived growth factor (PDGF), which play central roles in promoting fibroblast activity and collagen deposition. By targeting rapidly proliferating cells at the wound site, especially immature fibroblasts and inflammatory cells, radiotherapy disrupts the cycle of excessive scar formation and helps stabilize the wound healing process before abnormal fibrosis can reinitiate^[7,17,35].

Excision methods for keloids vary in technique, resulting in different biological effects on wound healing. A more recent method of excision, keloid intralesional excision (KILE) was introduced and presented a distinct surgical strategy compared to conventional extralesional excision. KILE removes the fibrotic core selectively while preserving the overlying epidermis and dermis. Therefore, it maintained the vascular integrity, reducing wound tension, and potentially modulating the fibroproliferative wound-healing response. A recent meta-analysis by Lawera et al. of 608 patients showed the anti-recurrence effect of KILE with a pooled recurrence rate of approximately 13% following KILE without postoperative radiotherapy, which is substantially lower than recurrence rates reported for excision alone^[36]. These findings showed that KILE itself functions as an active recurrence-reducing intervention rather than a variant of excision. Although the meta-analysis by Lawera et al. was not incorporated into the present quantitative analysis due to the differences in study scope and interventions, its findings highlight the influence of the surgical technique of keloid excision on recurrence outcome^[36].

There is consensus that the biologically effective dose (BED) for optimal keloid control should exceed 28-30 Gy, calculated using an α/β ratio of 10, appropriate for early-responding tissues such as keloids^[37]. Studies demonstrate that recurrence rates are significantly reduced when BED ≥ 30 Gy is achieved^[38]. For example, treatment protocols that deliver 20 Gy in 5 fractions or 18 Gy in 3 fractions consistently show recurrence rates of less than 10%. In contrast, doses below this threshold are associated with higher rates of treatment failure. Importantly, increasing the dose beyond 30 Gy does not provide any additional benefits and may instead increase the risk of adverse effects. Treatment delivery methods and fractionation schemes have evolved to strike a balance between effectiveness and safety. Electron beam therapy is often preferred because of its favorable depth-dose profile, which confines the radiation effects to the dermal layers while minimizing exposure to the underlying tissues^[7].

The timing of radiotherapy initiation post-excision is crucial for maximizing its efficacy. Hintz et al. suggested that delaying radiotherapy after excision might benefit keloid treatment by enhancing radiosensitization during the proliferative phase of cell growth, though immediate treatment is effective mainly for earlobe keloids^[39]. Conversely, studies show starting radiotherapy within 24 h post-surgery can reduce recurrence by 10% to 23% by inhibiting fibroblast proliferation, leading to the common practice of early initiation to minimize the chance of recurrence. As a result, radiotherapy is now commonly initiated within 24 h after surgical excision^[16,40,41].

However, the approach to postoperative radiotherapy for treating keloids has shifted from a generic 15 Gy in three fractions to individualized regimens. Initially, the generic protocol had revealed over 35%-40% recurrence rates, particularly at high-risk areas such as the scapula and chest front. To minimize that, in 2003, they instituted a protocol of dose boosts for higher recurrence sites to 20 Gy over four days and reduced doses for less recurrence sites (e.g., the earlobe) to 10 Gy over two days. That lowered recurrence rates significantly. Subsequent changes in 2013 refined the treatment by lessening sessions: higher recurrence sites received 18 Gy over three days, the earlobe 8 Gy as a single-day dose, and all others 15 Gy over two days. Those changes maintained the treatment at an efficacy level, reaching less than 10% for total recurrence, emphasizing the need for individualization of treatment based on localization of keloids and recurrence risk^[7].

In circumstances where adjuvant radiotherapy is not aligned with patient-specific factors or local resource constraints, multiple non-radiation options remain part of contemporary keloid management, including silicone/pressure-based therapies, intralesional agents (most commonly corticosteroids, with adjuvant options such as 5-fluorouracil, bleomycin, or verapamil), cryotherapy/cryosurgery, and laser-based approaches. Evidence syntheses and practice guidelines generally support intralesional corticosteroids as a core modality, with combination regimens (e.g., corticosteroid plus 5-fluorouracil) frequently reported to improve response in refractory lesions and reduce recurrence when used as adjuvant therapy. Laser modalities (e.g., pulsed-dye laser or ablative lasers) are commonly used as adjuncts, either to improve vascularity/erythema and scar texture or to enhance drug penetration when combined with intralesional or topical therapies. Cryotherapy has also been described as an effective option and is recommended in some guidelines particularly in combination with intralesional corticosteroids. Nevertheless, the comparative effectiveness of these alternatives vs. adjuvant radiotherapy for auricular keloids remains heterogeneous across the literature, so selection should be individualized based on lesion characteristics, prior recurrence, anatomic subunit, access to modalities, and patient preference within shared decision-making^[3,42,43].

The systematic review and meta-analysis evaluated recurrence rates following surgical excision of auricular keloids with and without reconstruction by flaps in combination with postoperative radiotherapy. In this review, the pooled recurrence proportion was 7.8% (95%CI: 0.0%-16.0%) in studies of excision with flap reconstruction plus postoperative radiotherapy and 20.0% (95%CI: 5.2%-34.8% in studies of excision plus postoperative radiotherapy without flap. Differences in the anatomical distribution of lesions across studies may partially confound the apparent benefit observed in the flap subgroup. The excision group also demonstrated higher heterogeneity (I² = 90%) than the flap subgroup (I² = 72%), suggesting greater variability among studies evaluating excision-based approaches. This heterogeneity may be attributable to variations in surgical techniques, patient selection, radiotherapy protocols, and follow-up duration. Accordingly, technique-based comparisons should be interpreted cautiously, particularly in the absence of direct comparative designs^[23-25]. Descriptive subgroup summaries show variability in reported recurrence by modality, dose schedules, and treatment timing. Electron-beam radiotherapy was the most frequently reported modality, while non-electron techniques were less commonly represented and heterogeneous. Across the included evidence base, radiotherapy regimens and reporting practices varied substantially, and key clinical factors that may drive treatment selection (e.g., lesion complexity, prior recurrence, auricular subunit, and wound tension) were inconsistently captured. As a result, the subgroup patterns should be interpreted as study-level signals rather than comparative effects, reinforcing the need for standardized reporting of radiotherapy parameters and recurrence definitions in future controlled studies.

The included studies reported minimal and generally manageable complications. Reported adverse effects in the excision group included hyperpigmentation and hypertrophic scarring, while in flap-based reports, a single instance of postoperative flap congestion was described. Reconstructive flap techniques are used to achieve stable wound closure and redistribute wound tension, which may influence postoperative healing and scar behavior. Radiotherapy was generally well tolerated in the majority of studies, with only mild skin reactions reported in selected cases. However, safety reporting in the included literature primarily reflects short-term toxicity and selected late benign effects, with heterogeneous definitions and follow-up duration across studies. While acute reactions were generally mild in reported series, the available evidence base is not designed to quantify rare late outcomes. In particular, radiation-associated malignancy risk cannot be reliably estimated from these studies due to limited follow-up, inconsistent oncologic outcome reporting, and the rarity of such events. Although one study reported a case of lung carcinoma following radiotherapy, no such events were observed in other included studies.

Postoperative radiotherapy following excision surgery may offer advantages in reducing recurrence and improving patient outcomes. Early administration of radiotherapy, particularly within 24 h after surgery, has been suggested to interfere with the early inflammatory cascade involved in keloid pathogenesis. When combined with flap reconstruction, which redistributes mechanical tension away from wound edges, this approach may address both biological and biomechanical contributors to keloid recurrence. Patients treated with flap reconstruction have also reported less skin irritation and discoloration, which may reflect improved tissue perfusion and vascularity within the flap, potentially enhancing radiation tolerance^[24,44]. Consequently, this combined approach not only mitigates the risk of recurrence but also promotes improved wound healing and aesthetic satisfaction. However, interpretation of these findings should consider the very low certainty of evidence for recurrence outcomes as assessed by the GRADE framework. Although pooled analyses suggest lower recurrence following flap reconstruction with adjuvant radiotherapy, the predominance of non-randomized studies, substantial heterogeneity, and limited adjustment for confounding preclude definitive causal inference. Accordingly, these results should be interpreted as hypothesis-generating and warrant confirmation in well-designed comparative studies.