Skip to main content
Download PDF

Incidence and predictors of lower extremity lymphedema after postoperative radiotherapy for prostate cancer

Radiation Oncology volume 20, Article number: 41 (2025) Cite this article

Abstract

Background

To assess the rate and predictors of lower extremity lymphedema (LEL) after radiotherapy (RT) following radical prostatectomy (RP) ± pelvic lymph node dissection (PLND) for prostate cancer.

Methods

Patients (pts) treated with adjuvant or salvage RT after RP ± PLND and a minimum 2-year follow-up were included. LEL was defined as a volume difference ≥ 10% between limbs evaluated using circumferential measurements with a flexible non-stretch tape. The following predictors were investigated at logistic regression: age (continuous); body mass index (BMI, continuous); exercise level (low vs. medium/high); smoking (yes vs. no); cigarette pack/year (continuous); hypertension (yes ns no); vascular comorbidity (yes vs. no); diabetes (yes vs. no); PLND (yes vs. no); number of examined nodes (continuous); whole pelvis radiotherapy (WPRT) (yes vs. no); time between RP and RT (continuous); planning target volume (PTV) volume (continuous); PTV/BMI (continuous). Statistical significance was claimed for p < 0.05.

Results

101 pts were examined. The median time from surgery to RT was 36.1 months (mths) (IQR: 15.0-68.3), the median time from RT to the date of study examination was 51.1 months (IQR: 36.8–65.3). 14 pts developed LEL (13.9%), 3 pts (2.9%) before RT, 11 pts (10.8%) after RT. The median time from RT to LEL was 4 mths (IQR: 0.5–17.3). At multivariable analysis (MVA) diabetes mellitus (DM) (OR = 32.8, p = 0.02), time between surgery and RT (OR = 0.966, p = 0.039) and exercise (OR = 0.03, p = 0.002) were independently correlated to LEL. The number of examined nodes was highly correlated to LEL at univariate analysis (OR = 1.066, p = 0.025) but was not confirmed at MVA (p = 0.719). Interestingly, the distribution of the examined nodes was statistically different between pts with low (median N = 12) vs. medium/high (N = 5) exercise (p = 0.034).

Conclusions

Clinically detectable LEL involves a minority of pts after RT. DM is a predisposing factor, while awaiting RT delivery has a protective effect favoring salvage over adjuvant RT.

Background

Secondary lymphedema (LE) is an important complication after oncological treatments that can have a major impact on patient’s quality of life. Several studies have evaluated the potential risk factors and the prevalence of LE after breast and gynecological cancers ranging between 0 and 50% [1, 2]. Patients treated for prostate cancer (PCa) can develop lower limb lymphedema (LEL), as a consequence of either radical prostatectomy (RP) or radiotherapy (RT). In addition to RP, extended pelvic lymph-node dissection (ePLND), which is recommended according to current guidelines in high- and intermediate-risk PCa patients when the estimated risk for positive lymph nodes exceeds 5% [3,4,5], can increase the risk of developing LEL as well [6, 7]. Moreover, following RP, adjuvant (aRT) and early salvage RT (sRT) are thought to further increase the risk of LEL [8,9,10,11]. According to a recent systematic review the prevalence of LEL is highest (18–29%) in patients undergoing pelvic RT after ePLND, confirming the potential cumulative effect of the combination of these two treatments [12].

The diagnosis of LEL is mainly clinical and the detection is based on measurements of limbs circumference and their volume. Clinically it can present with abnormal tissue swelling, limb heaviness, erythema, pain, impaired limb function [13]. A better knowledge of the prevalence and the risk factors related to LEL can guide patient’s treatment decision and can help make an early diagnosis, which is crucial for the treatment of this condition. Indeed, LEL can be successfully treated with bandages, lymphatic drainage and physical therapy when identified in its early stages, but once chronic and advanced often becomes untreatable [12, 13].

The aim of this study was to assess the rate and the predictors of LEL after RT following RP ± PLND.

Materials and methods

In this cross-sectional study, patients treated with aRT or sRT at a single Institution between 2000 and 2020 were offered participation. Patients were extracted from a prospectively maintained database based on the following selection criteria: (1) Upfront RP +/- PLND; (2) Subsequent aRT or sRT; (3) A minimum 2 year follow up after RT.

Regarding surgery, selected patients underwent prophylactic PLND. The anatomical extent of PLND was based on both surgeon decision and the year of surgery, with recent PLNDs being more extensive [14]. aRT was generally offered to patients with prostate specific antigen (PSA) persistence after RP and/or pathological (p)T3b stage and/or pN1 disease at surgery. An early sRT approach was offered to patients with undetectable PSA and < pT3b/pN1 disease stage at surgery. In the early sRT strategy, patients were considered biochemically failed with at least 2 consecutive PSA values equal or above 0.2 ng/ml [15]. In the latter case, restaging with both dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and positron emission tomography/computed tomography (PET/CT) was offered. RT consisted in 66 Gy (aRT) or 69 Gy (sRT) to the whole prostatic fossa in 30 fractions (fxs). Macroscopic local disease, when identified at DCE-MRI, was prescribed 73.5 Gy with a simultaneous integrated boost technique in 30 fxs, as previously reported [16, 17]. When treated, the pelvic nodes (bilateral internal, external and common iliac lymph nodes as well as presacral lymph nodes) were prescribed with 54 Gy in 30 fractions [18, 19]. In patients with positive lymphnodes at the histopathologic exam the total dose to the surgical bed containing the positive node was raised. A 60–66 Gy boost was delivered to patients with pN1 or those with subsequent positive lymph nodes undergoing sRT. All treatments were delivered in 30 fractions using a simultaneous integrated boost technique. Patients were simulated and treated in the supine position with an empty rectum and a semi full bladder.

Lymphedema examination

Patients who agreed to participate to the study were invited for a supplementary follow up examination focusing on LEL. Patients were asked whether they were currently experiencing any sign or symptoms of LEL: lower extremity swelling, heaviness, thickness, tiredness, or pain. Evaluation of LEL, as well as the calculation of both limb volume and stage were based on the measurement of the lower extremity circumference as recommended by the International Society of Lymphology (ISL) [20]. Limb volume measurement was performed with the patient in the supine position at multiple levels, starting caudally 2 cm above the middle of the medial malleolus on the medial aspect of the leg and then at 4 cm intervals above the starting point up to 2 cm below the popliteal fossa. The circumference at each mark was measured with the limb in a supine position placing the top edge of the tape measure just below the mark [21]. The same process was repeated on the contralateral limb. The measurements of limb volume were calculated as the sum of each geometric segment using the frustum model [22, 23]. The difference in volume between the two limbs was expressed as percentage relatively to the smaller one. The endpoint of the study was the development of LEL defined as a volumetric difference between the two limbs ≥ 10% in case of unilateral LEL, and defined by the ISL staging system [20] in case of a difference between the two limbs < 10% or in case of bilateral LEL. The ISL staging system system relies on a three stage scale (I-III), with higher stages for higher severity of LEL [20]. Stage I is an initial collection of fluid with a high protein content, possibly with the association with pitting. This stage can be considered as transitory, since the collection of fluid can decrease when the limb is elevated. Stage II LEL encompasses changes in solid structures, with pitting, but limb elevation rarely reduces tissue swelling. Finally, Stage III includes lymphostatic elephantiasis, which may lack pitting and is characterized by trophic skin changes.

Other variables hypothetically related to LEL were investigated: health factors such as body mass index (BMI), smoking habits and comorbidities (hypertension, cardiopathies, diabetes mellitus (DM)). The amount of physical exercise after RT was also investigated and scored according to the Italian version of the International Physical Activity Questionnaire, IPAQ-2005 [24]. For patients with physical activity limitation due to LEL, the questionnaire was referred to the time period before the onset of the impairment.

Statistical analysis

To describe the cumulative incidence of LEL over time after surgery (specifically at 1-, 5- and 10-year) we used the Kaplan Meier method. Conversely, to investigate predictors of LEL, we run univariable logistic regression models. Several covariates were considered: BMI, smoking habits and comorbidities such as hypertension, cardiopathies, DM (yes vs. no). According to literature, we have used 15 as the cutoff for define the extension of lymphadenectomy [4].

Associations were summarized by calculating odds ratios (ORs) and corresponding 95% confidence intervals (95%CI) from the model parameter estimates. Only significant variables were included in the multivariate analysis (MVA). P values less than 0.05 were deemed statistically significant. All statistical tests were performed using SPSS, version 25, software (SPSS Inc, Chicago, IL).

Results

Patients and treatment characteristics

101 patients agreed to participate to the present study. Selected patient, disease, and treatment characteristics are summarized in Table 1. The median age at the time of diagnosis was 65-year-old (IQR: 58–69-year-old). Median BMI was 26.1 kg/m2 (IQR:24.4–29 kg/m2) and approximately 16.8% of patients were obese (BMI ≥ 30 kg/m2). RP with PLND were performed in 69.3% (N = 70) of patients with a median of 12.5 (IQR: 8-17.2) pelvic lymph nodes removed. Notably, only 27.7% (N = 28) had more than 15 lymph nodes removed. In 2.9% (N = 3) of the 101 patients, the postoperative histopathologic analysis showed positive lymph nodes. The median time interval between surgery and RT was 36.1 months (IQR: 15.0-68.3 months). RT to the prostatic fossa was administered to all patients while whole pelvis radiotherapy (WPRT) was limited to 69 (68.3%) patients. Treatment details are illustrated in Table 2. The median radiation dose delivered to the prostate bed and to the pelvic lymph nodes was 69 Gy and 54 Gy respectively. The median duration of RT was 6 weeks. Seven patients (6.9%) received an additional RT boost to positive lymph nodes at histopathologic exam with a median total dose of 60 Gy.

Table 1 Patients characteristics
Full size table
Table 2 Radiotherapy characteristics
Full size table

Characteristics and incidence of LEL

At a median follow-up time of 85.3 months (IQR: 61.1–121) after RP, 14 patients (13.9%, 95% CI: 8.4–21.9%) were experiencing LEL. In 13 patients LEL was unilateral, in 1 patient was bilateral. Based on patients recalls in 3/14 patients (21.4%) LEL occurred before RT while the remaining 11 patients (78.6%) developed LEL after RT. For the latter group, median time from the end of RT to the onset of LEL was 23.8 months (IQR: 9.2–36.5). Figure 1 shows the actuarial cumulative incidence of LEL from the date of surgery with 1-year, 5-year, and 10-year rates of 4.0% (95%CI 1.5–10.2%), 11.9% (95%CI 6.9–20.0%) and 15.3% respectively (95% CI: 9.2–24.9%).

Fig. 1
figure 1

Estimated cumulative incidence rates of LEL

Full size image

Selected characteristics of LEL events are shown in Table 3. The median absolute volume and percentage relative differences between limbs in patients with LEL were 14.1 ml (IQR: 12.3–20.5 ml) and 14.1% (IQR:12.3–20.5%) respectively. According to the ISL classification 6 patients had stage I LEL, 6 patients had stage II, 1 patient had stage III, while none had stage IV. Eight out of 14 patients with LEL received bandage or lymphatic drainage as treatment.

Table 3 Lymphedema characteristics
Full size table

Predictors of LEL

Univariate analysis results are shown in Table 4. Among the clinical parameters investigated, age at diagnosis (continuum), DM (yes vs. no), smoking (yes/no and pack year) and the level of exercise after RT (moderate vs. low/ high vs. low/ moderate-high vs. low) were significantly associated with LEL. The number of lymphnodes removed during surgery was highly correlated to LEL at univariate analysis (UVA) (p = 0.02; OR:1.06; 95%CI: 1.00-1.12) and the subgroup with > 15 vs. none/<15 had a borderline effect (p = 0.05; OR:3.14 95%CI: 0.98–9.99). The cut-off of 15 lymphnodes removed was decided according to the extension of pelvic lymphadenectomy: limited PLND (< 15) versus extended PLND (> 15) [4]. Among the treatment variables tested, radiation boost to positive lymphnodes (yes vs. no, p = 0.03; OR:5.65; 95%CI: 1.11–28.7) and the time between RP and RT (> 40 vs. < 40 months, OR: 0.16; 95%CI: 0.03–0.77, p = 0.02) were associated with the risk of developing LEL. At MVA, the following predictors were significantly correlated with LEL: DM (OR: 32.8, 95%CI: 1.73–622 p = 0.02), the time between surgery and RT (OR:0.96, 95%CI: 0.93-0-99 p = 0.03) and level of exercise (OR:0.03, 95%CI: 0.01–0.29 p = 0.01). Smoking had a borderline effect (OR:4.8, p = 0.05) (Table 5), while pack/year, n. of lymphnodes removed and RT boost were not significantly correlated (p = 0.81, 0.86 and 0.71 respectively).

Table 4 Univariate analysis of risk factors associated with lymphedema
Full size table
Table 5 Multivariate analysis of risk factors associated with lymphedema
Full size table

Discussion

Secondary LEL can be an invalidating side effect for patients treated with RT following RP ± PLND. Defining the precise incidence of LEL is challenging due to the lack of standardized diagnostic criteria and a uniform definition of this condition. Here we have reported the incidence and the predictors of LEL in a retrospective series of 101 PCa patients treated with RT at our Institution, using the measurement of the lower extremity circumference as recommended by the ISL. In our series, the incidence of LEL was relatively limited (≈ 15%) despite the combination of surgery and RT. Most (≈ 80%) events were observed after surgery and RT, though surgery alone can be the cause, as we found in 3/14 patients (21.4%). After RT, LEL is a relatively early side effect being observed in the majority of cases within 3 years since treatment. Indeed, LEL typically occurs within the first 12–24 months after the surgical insult to lymphatic vessels and often becomes chronic with increasing degrees of severity and disability over time [25]. The surgery insult can modify the lymphatic system resulting in plasma and fluids accumulation in the interstitial compartment, with adipose deposition, chronic tissue inflammation and fibrosis [12, 26], with all of these modifications being a predisposing factor for the further effects of RT. In fact, the correlation between surgery and RT and the onset of lower lymphedema has been widely demonstrated in the literature. Several studies on breast and gynecological cancers have reported that sentinel lymphnode biopsy, lymphadenectomy and the number of dissected lymphnodes are risk factors for developing LE. The addition of RT to axillary lymph-node sampling with partial or total lymphadenectomy increases the risk of LE from 9% to over 40% [27, 28]. The results of the study of Volpi et al. confirmed that the extent of para-aortic lymphadenectomy is significantly correlated with the risk of LEL in patients with endometrial cancer (p < 0.001, OR:5.06, 95%CI: 1.6–15.9) [29]. In another series from the Memorial Sloan-Kettering, the rate of LEL was 3.4% and was limited to women with > 10 lymphnodes removed [30]. In a recent systematic review by Clinckaert et al. [12] the prevalence of LEL in PCa ranges from 0 to 14% in patients who underwent PLND and from 0 to 8% in patients treated with pelvic RT. Furthermore, LEL was even higher in the subgroup that underwent PLND + RT with a prevalence of 18–29%. According to the literature the rate of postoperative LEL is higher in the setting of PCa patients receiving PLND compared to other malignancies undergoing the same procedure [31, 32]. In the study of Forman et al. 12/41 (29.2%) patients who underwent PLND developed LEL compared to 5/199 (2.5%) patients who did not have PLND [33]. Morizane et al. found a statistically significant difference (p < 0.001) in LEL rate between patients undergoing extended PLND (6%) versus the limited PLND group (1%) [7]. Accordingly, in our study the number of examined nodes was highly correlated to LEL at univariate analysis (OR = 1.066, p = 0.025). However, this was not confirmed at MVA (p = 0.719). Interestingly, the distribution of examined nodes was statistically different between patients with low (median N = 12) vs. medium/high (N = 5) exercise (p = 0.034) speculating that exercise level could be more a consequence of the extent of pelvic surgery rather than a cause of LEL.

In our series we have found a median of 12.5 lymph-nodes removed and a 13.8% LEL rate. Similarly, Achouri et al. reported a rate of LEL of 11.4% with a mean of 12 lymph-nodes removed [34]. When evaluating the timing of the onset of LEL, 3 patients already presented with LEL before RT, identifying an actual rate of LEL after treatment of 10.8% (N = 11) in our cohort.

RT has been found to be a major independent risk factor for the development of LE in several studies, and regional irradiation is considered as the strongest one [32, 35, 36]. In contrast, Rasmusson E. et al. [37] showed that brachytherapy and pelvic external beam RT have low incidence of LEL, and in their series there was no correlation between RT treatment volumes and LEL. In our study the addition of WPRT was not significantly related to LEL (p = 0.78, OR:1.186) at UVA, as well as the amount of the planning target volume (PTV) (p = 0.87, OR:1.00).

As reported in the literature, other risk factors related to LEL are the following ones: lymphocyst formation [38], level of exercise [39], BMI [40, 41] and DM [2, 41]. Based on our results both level of exercise (p = 0.01, OR: 0.03, 95%CI:0.01–0.29) and DM (p = 0.02, OR: 32.8, 95%CI: 1.73–622) were confirmed to be significant independent predictors for the onset of LEL.

LEL rate could also be affected by cardio-vascular comorbidity, but in our series, we have found no correlation with hypertension, cardiopathies and BMI at UVA.

Another interesting finding is that the time interval < 40 months between surgery and RT was a significant risk factor for developing LEL at MVA (p = 0.03, OR 0.96 95%CI: 0.93–0.99). This could be considered as another clinical reason for delaying RT after RP, thus favoring sRT over aRT, in addition to the recent published long-term results of the RADICALS-RT trial (NCT00541047) [42] where aRT is confirmed to be associated with increase urinary and bowel toxicity without improvement in disease control.

LEL can be considered as a multifactorial process that starts through PLND surgery, which modifies the normal lymphatic system, and becomes visible after radiotherapy, which worsens lymphatic drainage with tissue fibrosis. Therefore, a better understanding of the prevalence of LEL after PCa therapy is important for pre-operative counseling of patients, to facilitate an early diagnosis and to start LEL therapies.

Most of the studies available in the literature are based on retrospective cohorts, and were not designed to assess LEL as the primary outcome identified with appropriate and accurate measurements, thus leading to the risk of early and moderate LEL neglection and, consequently, LEL incidence may be under-estimated. However, our study has some limitation: the retrospective nature of the study; the lack of information of the evolution of LEL over time after the follow-up examination; the fact that limb volume measurement was not possible when LEL was bilateral (N = 1), thus only the ISL stage was used in this case.

Finally, the date of LEL onset was identified during patient’s interview, which may have led to under/overestimation of the actual rate and course of LEL. Nevertheless, there are limited clinical data in the literature of incidence of LEL in patients who underwent RT following RP + PLND and the strengths of our investigation include the use of a validated instrument to detect LEL.

Conclusion

Clinically detectable LEL is a relatively infrequent side effect after combined surgery and radiotherapy with roughly 1 out of 10 patients showing LEL onset after RT following RP ± PLND. Diabetes a predisposing factor while awaiting RT delivery has a protective effect favoring salvage over adjuvant RT. The role of physical exercise along with the extent of pelvic surgery and the impact on quality of life needs to be prospectively investigated. Future work aiming at early detection and assessment of patients for LEL is also needed.

Data availability

The dataset(s) supporting the conclusions of this article is(are) available in the [LEL] repository, [file:///C:/Users/farina.ilaria/Downloads/LINF_SETT.html].”

Abbreviations

LE:

Secondary lymphedema

PCa:

Prostate cancer

LEL:

Lower limb lymphedema

RP:

Radical prostatectomy

RT:

Radiotherapy

ePLND:

Extended pelvic lymph-node dissection

aRT:

Adjuvant radiotherapy

sRT:

Early salvage RT

PSA:

Prostate specific antigen

DCE-MRI:

Dynamic contrast enhanced-magnetic resonance imaging

PET/CT:

Positron emission tomography/computed tomography

fxs:

Fractions

BMI:

Body mass index

DM:

Diabetes mellitus

ISL:

International Society of Lymphology

ORs:

Odds ratios

MVA:

Multivariate analysis

WPRT:

Whole pelvis radiotherapy

UVA:

Univariate analysis

References

  1. Bona AF, Ferreira KR, Carvalho RBM, Thuler LCS, Bergmann A. Incidence, prevalence, and factors associated with lymphedema after treatment for cervical cancer: a systematic review. Int J Gynecol Cancer. 2020;30(11):1697–704.

    Article  PubMed  Google Scholar 

  2. Yost KJ, Cheville AL, Al-Hilli MM, Mariani A, Barrette BA, McGree ME, Weaver AL, Dowdy SC. Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life. Obstet Gynecol. 2014;124(2 Pt 1):307–15.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, Bellmunt J, Bolla M, Cornford P, De Santis M, et al. The benefits and Harms of different extents of Lymph Node Dissection during Radical Prostatectomy for prostate Cancer: a systematic review. Eur Urol. 2017;72(1):84–109.

    Article  PubMed  Google Scholar 

  4. Lestingi JFP, Guglielmetti GB, Trinh QD, Coelho RF, Pontes J Jr., Bastos DA, Cordeiro MD, Sarkis AS, Faraj SF, Mitre AI, et al. Extended Versus Limited Pelvic Lymph Node Dissection during Radical Prostatectomy for Intermediate- and high-risk prostate Cancer: early oncological outcomes from a Randomized Phase 3 Trial. Eur Urol. 2021;79(5):595–604.

    Article  PubMed  Google Scholar 

  5. Gandaglia G, Mazzone E, Stabile A, Pellegrino A, Cucchiara V, Barletta F, Scuderi S, Robesti D, Leni R, Samanes Gajate AM, et al. Prostate-specific membrane antigen radioguided surgery to detect nodal metastases in primary prostate Cancer patients undergoing Robot-assisted radical prostatectomy and extended pelvic lymph node dissection: results of a planned interim analysis of a prospective phase 2 study. Eur Urol. 2022;82(4):411–8.

    Article  PubMed  Google Scholar 

  6. Zhang X, Zhang G, Wang J, Bi J. Different lymph node dissection ranges during radical prostatectomy for patients with prostate cancer: a systematic review and network meta-analysis. World J Surg Oncol. 2023;21(1):80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morizane S, Honda M, Fukasawa S, Komaru A, Inokuchi J, Eto M, Shimbo M, Hattori K, Kawano Y, Takenaka A. Comparison of the diagnostic efficacy and perioperative outcomes of limited versus extended pelvic lymphadenectomy during robot-assisted radical prostatectomy: a multi-institutional retrospective study in Japan. Int J Clin Oncol. 2018;23(3):568–75.

    Article  CAS  PubMed  Google Scholar 

  8. Briganti A, Chun FK, Salonia A, Suardi N, Gallina A, Da Pozzo LF, Roscigno M, Zanni G, Valiquette L, Rigatti P, et al. Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur Urol. 2006;50(5):1006–13.

    Article  PubMed  Google Scholar 

  9. Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, Williams SG, Brown C, Delprado W, Haworth A, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020;21(10):1331–40.

    Article  CAS  PubMed  Google Scholar 

  10. Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020;396(10260):1413–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sargos P, Chabaud S, Latorzeff I, Magne N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1341–52.

    Article  CAS  PubMed  Google Scholar 

  12. Clinckaert A, Callens K, Cooreman A, Bijnens A, Moris L, Van Calster C, Geraerts I, Joniau S, Everaerts W. The Prevalence of Lower Limb and Genital Lymphedema after Prostate Cancer Treatment: A Systematic Review. Cancers (Basel) 2022, 14(22).

  13. Fokdal L, Berg M, Zedan AH, Mortensen B, Nissen HD, Bentzen L, Svenson M, Madsen CV. Patient-reported lower limb edema after primary radiotherapy for prostate cancer. Acta Oncol. 2023;62(10):1279–85.

    Article  CAS  PubMed  Google Scholar 

  14. Roach M 3rd, Marquez C, Yuo HS, Narayan P, Coleman L, Nseyo UO, Navvab Z, Carroll PR. Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 1994;28(1):33–7.

    Article  PubMed  Google Scholar 

  15. Pisansky TM, Thompson IM, Valicenti RK, D’Amico AV, Selvarajah S. Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018–2019. J Urol. 2019;202(3):533–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sanguineti G, Bertini L, Faiella A, Ferriero MC, Marzi S, Farneti A, Landoni V. Response on DCE-MRI predicts outcome of salvage radiotherapy for local recurrence after radical prostatectomy. Tumori. 2021;107(1):55–63.

    Article  CAS  PubMed  Google Scholar 

  17. Faiella A, Sciuto R, Giannarelli D, Bottero M, Farneti A, Bertini L, Rea S, Landoni V, Vici P, Ferriero MC et al. A Prospective Study Assessing the Post-Prostatectomy Detection Rate of a Presumed Local Failure at mpMR with Either (64)CuCl(2) or (64)CuPSMA PET/CT. Cancers (Basel) 2021, 13(21).

  18. Lawton CA, Michalski J, El-Naqa I, Buyyounouski MK, Lee WR, Menard C, O’Meara E, Rosenthal SA, Ritter M, Seider M. RTOG GU Radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2009;74(2):383–7.

    Article  PubMed  Google Scholar 

  19. Hall WA, Paulson E, Davis BJ, Spratt DE, Morgan TM, Dearnaley D, Tree AC, Efstathiou JA, Harisinghani M, Jani AB, et al. NRG Oncology Updated International Consensus Atlas on pelvic lymph node volumes for Intact and postoperative prostate Cancer. Int J Radiat Oncol Biol Phys. 2021;109(1):174–85.

    Article  PubMed  Google Scholar 

  20. Executive Committee of the International Society of L. The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology. 2020;53(1):3–19.

    Google Scholar 

  21. Lymphoedema framework. Best Practice for the Management of Lymphoedema. International consensus. In., edn. London: Mep ltd 2006; 2006.

  22. Sander AP, Hajer NM, Hemenway K, Miller AC. Upper-extremity volume measurements in women with lymphedema: a comparison of measurements obtained via water displacement with geometrically determined volume. Phys Ther. 2002;82(12):1201–12.

    Article  PubMed  Google Scholar 

  23. Chromy A, Zalud L, Dobsak P, Suskevic I, Mrkvicova V. Limb volume measurements: comparison of accuracy and decisive parameters of the most used present methods. Springerplus. 2015;4:707.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Minetto MA, Motta G, Gorji NE, Lucini D, Biolo G, Pigozzi F, Portincasa P, Maffiuletti NA. Reproducibility and validity of the Italian version of the International Physical Activity Questionnaire in obese and diabetic patients. J Endocrinol Invest. 2018;41(3):343–9.

    Article  CAS  PubMed  Google Scholar 

  25. Franchi M, Ghezzi F, Riva C, Miglierina M, Buttarelli M, Bolis P. Postoperative complications after pelvic lymphadenectomy for the surgical staging of endometrial cancer. J Surg Oncol. 2001;78(4):232–7. discussion 237–240.

    Article  CAS  PubMed  Google Scholar 

  26. Cemal Y, Jewell S, Albornoz CR, Pusic A, Mehrara BJ. Systematic review of quality of life and patient reported outcomes in patients with oncologic related lower extremity lymphedema. Lymphat Res Biol. 2013;11(1):14–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14(6):500–15.

    Article  PubMed  Google Scholar 

  28. Chandra RA, Miller CL, Skolny MN, Warren LE, Horick N, Jammallo LS, Sadek BT, Shenouda MN, O’Toole J, Specht MC, et al. Radiation therapy risk factors for development of lymphedema in patients treated with regional lymph node irradiation for breast cancer. Int J Radiat Oncol Biol Phys. 2015;91(4):760–4.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Volpi L, Sozzi G, Capozzi VA, Ricco M, Merisio C, Di Serio M, Chiantera V, Berretta R. Long term complications following pelvic and para-aortic lymphadenectomy for endometrial cancer, incidence and potential risk factors: a single institution experience. Int J Gynecol Cancer. 2019;29(2):312–9.

    Article  PubMed  Google Scholar 

  30. Abu-Rustum NR, Alektiar K, Iasonos A, Lev G, Sonoda Y, Aghajanian C, Chi DS, Barakat RR. The incidence of symptomatic lower-extremity lymphedema following treatment of uterine corpus malignancies: a 12-year experience at Memorial Sloan-Kettering Cancer Center. Gynecol Oncol. 2006;103(2):714–8.

    Article  PubMed  Google Scholar 

  31. Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr., Wells N, Smith J Jr. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol. 2003;169(1):145–7. discussion 147–148.

    Article  PubMed  Google Scholar 

  32. Pilepich MV, Perez CA, Walz BJ, Zivnuska FR. Complications of definitive radiotherapy for carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 1981;7(10):1341–8.

    Article  CAS  PubMed  Google Scholar 

  33. Forman JD, Zinreich E, Lee DJ, Wharam MD, Baumgardner RA, Order SE. Improving the therapeutic ratio of external beam irradiation for carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 1985;11(12):2073–80.

    Article  CAS  PubMed  Google Scholar 

  34. Achouri A, Huchon C, Bats AS, Bensaid C, Nos C, Lecuru F. Complications of lymphadenectomy for gynecologic cancer. Eur J Surg Oncol. 2013;39(1):81–6.

    Article  CAS  PubMed  Google Scholar 

  35. Allam O, Park KE, Chandler L, Mozaffari MA, Ahmad M, Lu X, Alperovich M. The impact of radiation on lymphedema: a review of the literature. Gland Surg. 2020;9(2):596–602.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mitra D, Catalano PJ, Cimbak N, Damato AL, Muto MG, Viswanathan AN. The risk of lymphedema after postoperative radiation therapy in endometrial cancer. J Gynecol Oncol. 2016;27(1):e4.

    Article  PubMed  Google Scholar 

  37. Rasmusson E, Gunnlaugsson A, Blom R, Bjork-Eriksson T, Nilsson P, Ahlgen G, Jonsson C, Johansson K, Kjellen E. Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer. Radiat Oncol. 2013;8:271.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kuroda K, Yamamoto Y, Yanagisawa M, Kawata A, Akiba N, Suzuki K, Naritaka K. Risk factors and a prediction model for lower limb lymphedema following lymphadenectomy in gynecologic cancer: a hospital-based retrospective cohort study. BMC Womens Health. 2017;17(1):50.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hayes SC, Janda M, Ward LC, Reul-Hirche H, Steele ML, Carter J, Quinn M, Cornish B, Obermair A. Lymphedema following gynecological cancer: results from a prospective, longitudinal cohort study on prevalence, incidence and risk factors. Gynecol Oncol. 2017;146(3):623–9.

    Article  PubMed  Google Scholar 

  40. Greene AK, Zurakowski D, Goss JA. Body Mass Index and Lymphedema Morbidity: comparison of obese versus normal-weight patients. Plast Reconstr Surg. 2020;146(2):402–7.

    Article  CAS  PubMed  Google Scholar 

  41. Leitao MM Jr., Zhou QC, Gomez-Hidalgo NR, Iasonos A, Baser R, Mezzancello M, Chang K, Ward J, Chi DS, Long Roche K, et al. Patient-reported outcomes after surgery for endometrial carcinoma: prevalence of lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy. Gynecol Oncol. 2020;156(1):147–53.

    Article  PubMed  Google Scholar 

  42. Parker CC, Petersen PM, Cook AD, Clarke NW, Catton C, Cross WR, Kynaston H, Parulekar WR, Persad RA, Saad F et al. Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047). Ann Oncol 2024.

Download references

Acknowledgements

Not applicable.

Funding

This work was financially supported through funding from the institutional "Ricerca Corrente" granted by the Italian Ministry of Health.

Author information

Author notes

  1. Giuseppe Facondo and Marta Bottero equally contributed to this work.

Authors and Affiliations

  1. Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Giuseppe Facondo, Marta Bottero, Lucia Goanta, Alessia Farneti, Adriana Faiella, Pasqualina D’Urso & Giuseppe Sanguineti

Authors
  1. Giuseppe Facondo
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Marta Bottero
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Lucia Goanta
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Alessia Farneti
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Adriana Faiella
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Pasqualina D’Urso
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Giuseppe Sanguineti
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Conceptualization: G.S., G.F., M.B.; Data curation: G.F., L.G; Formal Analysis: G.S.; Investigation: G.F., L.G., M.B.; Methodology: G.S.; Project administration: G.S; Resources: A.F. (A.Farneti), P.D., A.F (A.Faiella); Supervision: G.S.; Validation: G.S., M.B.; Visualization: A.F. (A.Farneti), P.D., A.F (A.Faiella); Writing– original draft: G.S., G.F., M.B; Writing– review & editing: G.S., M.B, G.F.; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Marta Bottero.

Ethics declarations

Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the ‘Regina Elena’ National Cancer Institute (protocol code 946/17) and approved 13 June 2017.

Consent for publication

Informed consent was obtained from all subjects involved in the study.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Facondo, G., Bottero, M., Goanta, L. et al. Incidence and predictors of lower extremity lymphedema after postoperative radiotherapy for prostate cancer. Radiat Oncol 20, 41 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02599-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13014-025-02599-7

Keywords

Radiation Oncology

ISSN: 1748-717X

Contact us