The search of the four medical indices yielded a total of 48 articles (33 prospective studies and 15 systematic reviews), providing a total sample size of 234,079 cancer survivors (Fig. 1). Our search encompassed papers reporting on CRL according to any cancer type. However, only four categories of cancer were included breast, gynecological and urological, head and neck (H&N) and melanoma. A fifth category represented preventive lymphatic surgery aiming to reduced CRL incidence including lymphovenous anastomosis (LVA) and axillary reverse mapping (ARM).

Breast cancer studies were the most numerous (50%, n = 24) and provided 88.6% of the total study population. Gynecological and urological cancers represented 27.1% (n = 13) of the included articles, and 6.1% of the population. This was followed by preventive lymphatic surgery (12.5%, n = 6), mainly focussing on breast cancer patients, representing 4.3% of the total population. Melanoma and H&N cancers represented the lowest number of included articles with 6.3 and 4.2%, respectively, corresponding to 0.5 and 0.2% of the total population.

A total of nine clinical definitions were identified, whereby 43.8% of the studies used a difference of greater than 5–10% between the limbs to define lymphedema (Table 1). Additionally, some studies also used more than one definition when various methods of diagnosis were used. About a quarter of the studies (13 studies, 27%) did not specify their clinical definition of lymphedema.

Our review yielded a plethora of diagnostic methods, grouped into seven different methods, whereby most studies (30 studies, 62.5%) used circumferences and self-reported (16 studies, 33.3%) methods (Table 2). Several studies used more than one method of diagnosis, while two studies did not report diagnostic methods.

Subsequently, while extracting data, we were able to identify several trends regarding risk factors that might influence CRL incidence. Our findings suggest that the following could increase the risk of developing CRL: extensive surgery (e.g., tumor and/or lymph node dissection), increasing age, having received adjuvant therapy (both chemotherapy and radiation therapy), body mass index (BMI) greater than 25 or 30 at surgery and increasing post-treatment, insufficient physical activity levels, and post-surgical complications (e.g., lymphocele, wound infection, seroma). Conversely, education (preoperative and general about lymphedema), prospective surveillance with early identification of signs and symptoms, lymphedema risk reduction practices, weight management or weight reduction, scar tissue release and omission of axillary dissection, show a trend toward decreasing the risk of CRL.

A total of 15 prospective studies reporting on the incidence of breast cancer-related lymphedema (BCRL), representing nearly 15,000 patients, were identified (Table 3) [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]. Incidence findings were reported using either objective measures (limb circumference, Bio-Impedance Spectroscopy (BIS), perometry, Indocyanine Green (ICG)), or by self-report. Length of follow-up varied between 6 and 120 months.

For objective measures, BCRL incidence ranged from 2 to 60.3%. While the majority of studies (9 studies) utilized circumferential measurements to assess for lymphedema, variations in how lymphedema was defined were noted. Lowest incidence was reported with perometry and ICG at 24 months. For self-report, BCRL incidence ranged from 2.1 to 74.3%. Survivors treated with axillary lymph node dissection (ALND), chemotherapy and/or regional lymph node radiation reported a higher incidence of BCRL, varying between 2.9% (perometry and ICG) and 60.3% (circumference). Table 3 further highlights the heterogeneity of the findings reported for the breast cancer population.

Additionally, nine systematic reviews reporting on BCRL incidence met our inclusion criteria, encompassing a total of 283 articles and representing over 192,000 BCRL patients (Table 4) [40,41,42,43,44,45,46,47,48]. Some systematic reviews provided pooled lymphedema estimates, varying between 4 and 23.6%, and/or a variation in lymphedema incidence ranging from 0% to 63.4%.

Some systematic reviews presented lymphedema incidence based on the measurement technique used. Water displacement tends to report the lowest incidence (0–22.2%), followed by BIS (3.1–31.9%), self-report (0–54.0%), perometry (7.2–54.0%), and circumferences measurements (1–63.4%). As observed in prospective studies, ALND showed a higher incidence in the systematic reviews varying from 6 to 24.6%, compared to 3.7% to 7.5% for SLNB.

Eleven studies, with over 3200 patients, representing cervical, endometrial, ovarian, and vulvar malignancies were included (Table 5) [49,50,51,52,53,54,55,56,57,58,59]. The length of follow-up varied between 6 and 120 months, with the highest incidence of 45.1% self-reported by patients at 24 months. Incidence varied among the different types of gynecological cancers, with all of them reporting a lower incidence when neither lymph node dissection nor sentinel lymph node biopsy (SLNB) were performed. The highest incidence was reported by women treated for vulvar (66.7%), followed by cervical (51.7%), endometrial (44.4%), and ovarian (40.4%) cancer. Most studies assessing for lower limb lymphedema (LLL) post-gynecological cancers used circumferential measurements as an objective measure (Table 5).

One systematic review on prostate cancer [60] and one on vulvar cancer [61] were included with a total sample size of 11,758 patients (Table 6). For prostate cancer, Clinckaert et al. (2022) [60] reported LLL varying from 0 to 29%, and genital lymphedema varying from 0 to 22%, respectively. A higher incidence was found in those who underwent pelvic lymph node dissection (PLND) and radiotherapy. Huang et al. (2017) [61] provided a pooled LLL estimate of 28.8% in vulvar malignancies, with the highest incidence in cross-sectional studies (49.2%) or randomized controlled trials (45.1%).

A total of 380 participants, distributed in two studies were included (Table 7) [62, 63]. Participants of both studies received similar interventions. The incidence of H&N CRL tends to be higher in the early phase post-treatment, varying from 80 to 90.1%, while decreasing over time to 70.6–82.3%. Ridner et al. (2016) [62] reported that external lymphedema tends to vary between 81.9 and 90.1%, internal lymphedema between 80.4 and 89.4%, and a combination of both between 70.6 and 80.9%. Tribius et al. (2020) [63] reported an incidence of 80% between 3 and 6 months in advanced stage H&N cancer.

The three melanoma studies all distinguished between upper and lower limb lymphedema (Table 8) [64,65,66]. The overall CRL incidence varied between 2 and 28.6%, with the lowest incidence attributed to upper limb or trunk melanoma treated with SLNB (1.0–18.4%), and the highest to lower limb or trunk melanoma treated with “total” lymph node dissection (TLND) (7.7–47.4%). Only one study [65] had participants self-reporting an incidence of 23.1% at a median time of 37 months after SLNB in both upper and lower limb CRL.

Two prospective studies [67, 68] and four systematic reviews [69,70,71,72] on surgery aiming to prevent lymphedema were included, representing a total of 10,080 patients (Table 9). Preventive surgery included LVA or ARM procedures, in cases where full lymph node dissection was judged to be required. The reported CRL incidence was 16–28.5% and 5.2–23.4% for prospective studies and systematic reviews, respectively. Patients receiving the preventive procedure experienced a lower incidence of CRL compared to controls in both prospective studies and systematic reviews: 3–21% versus 19–42%, 2–18% versus 14.1–48.5%, respectively.