Abstract
Objective
We investigated patients who underwent robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND), analyzing the prevalence and risk factors associated with symptomatic lymphoceles (SLCs).
Methods
We evaluated 354 consecutive patients who underwent RARP with PLND by our team between June 2016 and December 2022. After analyzing the prevalence of SLCs, patients were divided into two groups, with and without SLCs. The variables were age, body mass index (BMI), prostate-specific antigen, surgery time, blood loss, length of stay, International Society of Urological Pathology score in the pathology, and the number of lymph nodes removed. These variables were compared between these groups using the Chi-square test and Student's t-test, according to the type of the variable. In all analyses, a significance level of <0.05 was considered.
Results
The prevalence of SLCs in this sample of patients undergoing RARP with PLND was 2.0% (7/354), which is slightly lower than the minimum rate reported in the literature. In our analysis, BMI (p=0.041), the number of lymph nodes removed (p=0.007), and length of hospital stay (p=0.007) were factors associated with the presence of SLCs.
Conclusion
The prevalence of SLCs in patients undergoing RARP with PLND is approximately 2.0%. Higher BMI, greater number of lymph nodes removed, and longer length of hospital stay are factors associated with the presence of SLCs.
Keywords: Lymphocele, Symptomatic lymphocele, Lymphadenectomy, Robot-assisted radical prostatectomy
1. Introduction
Prostate cancer is the second most prevalent cancer in men worldwide and robot-assisted radical prostatectomy (RARP) has emerged as the contemporary standard of care for nonmetastatic prostate cancer due to its promising oncological and functional outcomes [1,2]. Notably, RARP has supplanted open radical prostatectomy in numerous centers, largely due to its low perioperative morbidity.
Depending on the patient's risk profile, intraoperative pelvic lymph node dissection (PLND) is required as it offers a more accurate assessment of lymph node involvement, improving patient staging and follow-up [3,4]. Although the oncological benefits of extended PLND remain under debate, current guidelines advocate its implementation in patients with intermediate- and high-risk prostate cancer [3,4].
Among the potential complications after PLND, the most frequently encountered is the formation of lymphoceles (LCs), with incidence rates reported in the literature ranging from 2% to 61%, when detected by tomography [5,6]. These encapsulated collections of lymphatic fluid arise from surgical disruption of lymphatic vessels and improper closure, causing significant postoperative morbidity after radical prostatectomy [[5], [6], [7]]. Although most LCs remain asymptomatic, their clinical implications, ranging from infection and pelvic discomfort to lower urinary tract symptoms, lower limb edema, and venous thromboembolism, reinforce the need to prevent the formation of symptomatic LCs (SLCs) [[5], [6], [7]].
Previous studies have revealed SLC formation rates of up to 11.2% after radical prostatectomy with PLND, with slightly lower rates of up to 7.9% reported for RARP [[8], [9], [10]]. Although some studies have attempted to identify potential risk factors for SLC formation, most of these studies have evaluated open radical prostatectomy, resulting in limited data available for the robotic approach [[11], [12], [13], [14]]. Therefore, in this analysis of 354 consecutive patients undergoing RARP with PLND in a Brazilian high-volume surgical center, we analyzed the prevalence and factors associated with SLCs.
2. Patients and methods
The study is in accordance with the Helsinki Declaration and its amendments and was approved by the Ethics in Research Committee of Moriah Hospital, São Paulo, Brazil (registry: CAAE 67150222.4.0000.8054; approval number: 5.916.939).
In this study, all patients who underwent RARP with PLND by our team between June 2016 and December 2022 were evaluated. From patient data, we collected age, body mass index (BMI), preoperative prostate-specific antigen (PSA), surgeon time at the console, final aspirator volume, International Society of Urological Pathology (ISUP) score in pathology, high-grade tumor by ISUP (ISUP Grade 4 or 5), number of lymph nodes removed, extended PLND (more than 10 lymph nodes removed), presence of SLCs, and length of hospital stay. The normality of continuous variables was assessed using the Kolmogorov-Smirnov test.
The SLC was defined as a LC causing fever, abdominal pain, lower extremity pain and/or swelling, lower urinary tract symptoms, deep vein thrombosis, or pulmonary embolism. Patients with clinical symptoms of SLCs underwent CT scans of the abdomen and pelvis to confirm the diagnosis.
After analyzing the prevalence of SLCs, patients were divided into two groups, with and without SLCs, with the following variables: age, BMI, PSA, surgery time, blood loss, length of hospital stay, ISUP score in the pathology, and the number of lymph nodes removed, compared between these groups using the Chi-square test and Student's t-test, according to the type of the variable. In all analyses, a significance level of <0.05 was considered. The data were analyzed using the Stata program (Version 14, StataCorp, College Station, TX, USA).
3. Results
We reviewed data of 354 patients who underwent RARP during the period analyzed, with 2.0% (7/354) presenting SLCs as a postoperative complication. The baseline characteristics of the patients included in the study are summarized in Table 1. Of the seven cases of SLCs, one was classified as Clavien-Dindo Grade I (managed with symptomatic medication only), three as Grade II (treated with antibiotics), and three as Grade III (requiring percutaneous drainage).
Table 1.
Baseline characteristics of patients (n=354).
| Variable | Value |
|---|---|
| Age, year | 66.1±7.3 |
| BMI, kg/m2 | 27.9±4.7 |
| Preoperative PSA, ng/mL | 8.1±7.1 |
| Surgeon time at console, min | 134.4±44.2 |
| Final aspirator volume, mL | 312.5±232.8 |
| ISUP score in pathology | 2.95±1.17 |
| High-grade tumor by ISUP | 97 (27) |
| Lymph nodes removed, n | 15.14±11.15 |
| Extended PLND | 236 (67) |
| Symptomatic lymphocele | 7 (2.0) |
| Length of hospital stay, h | 25.26±6.25 |
| Length of hospital stay of >24 h | 72 (20) |
BMI, body mass index; ISUP, International Society of Urological Pathology; PLND, pelvic lymph node dissection; PSA, prostate-specific antigen.
Note: values are presented as mean±standard deviation or n (%).
The patients in the study were mostly elderly (over 60 years old) and were in the BMI range corresponding to overweight. More than a quarter of the patients had a high-grade tumor (ISUP Grade 4 or 5), with the mean preoperative PSA being 8.1 ng/mL (Table 1).
Among all patients, the mean number of lymph nodes removed in PLND was 15.14, and in 67% of cases, PLND was considered extended (more than 10 lymph nodes removed). The mean surgeon's time at the console and hospital stay were 134.4 min and 25.26 h, respectively (Table 1).
In our analysis, BMI (p=0.041), the number of lymph nodes removed (p=0.007), and length of hospital stay (p=0.007) were factors associated with the presence of SLCs (Table 2). These data suggest that the higher the BMI, the greater the number of lymph nodes removed, and the longer the length of hospital stay, the greater the chance of developing SLCs in the postoperative period.
Table 2.
Factors associated with the presence of SLCs.
| Variable | With SLCsa (n=7) | Without SLCsa (n=347) | p-Value |
|---|---|---|---|
| Age, year | 69.0±8.2 | 66.0±7.3 | 0.4 |
| BMI, kg/m2 | 31.1±1.9 | 27.8±4.8 | 0.041b |
| Preoperative PSA, ng/mL | 8.4±8.3 | 8.1±7.1 | 0.9 |
| Surgeon time at the console, min | 157.0±46.0 | 133.9±44.2 | 0.4 |
| Final aspirator volume, mL | 400±158.1 | 309.9±234.6 | 0.3 |
| ISUP score in pathology | 3.4±1.1 | 2.9±1.2 | 0.3 |
| Lymph nodes removed, n | 26.4±17.7 | 14.9±10.9 | 0.007b |
| Length of hospital stay, h | 33.5±12.9 | 25.1±5.9 | 0.007b |
BMI, body mass index; ISUP, International Society of Urological Pathology; PSA, prostate-specific antigen; SLC, symptomatic lymphocele.
Values are presented as mean±standard deviation.
Statistically significant.
4. Discussion
In this analysis of the prevalence and factors associated with SLCs after RARP with PLND in 354 patients, the main findings were: (1) the prevalence of SLCs after RARP with PLND was 2.0%, which is slightly lower than the minimum rate (2.3%) reported in the literature [5]; (2) the higher the patient's BMI, the greater the chance of developing SLCs; (3) the more lymph nodes removed during lymphadenectomy, the greater the chance of developing SLCs; and (4) patients who stay in hospital longer after surgery also have a greater chance of developing SLCs.
The influence of the surgical technique on SLC formation is still unclear [12]. Although some studies have shown a difference in the prevalence of SLCs between open and robotic prostatectomy [12,14], another study has not supported this relationship [15]. Not only the access route, but also other aspects of the surgical technique, such as the use of clips or electrocautery during dissection, need to be elucidated. The low prevalence of SLCs in our sample is possibly due to a dissection and hemostasis technique in RARP and PLND performed only with electrocautery. Another factor that may have contributed to the low prevalence of SLCs in our study was the non-adoption of routine antithrombotic prophylaxis with low molecular weight heparin, as this is a known predictor of LCs in the literature [12]. In our center, antithrombotic prophylaxis with heparin is performed in accordance with the European Association of Urology guidelines on thromboprophylaxis in urological surgery, being recommended for RARP with PLND in patients at high risk of thromboembolism and RARP with extended PLND in patients with medium or high risk of thromboembolism [16].
Several articles in the literature have shown the relationship between the number of lymph nodes removed during PLND and the prevalence of LCs or SLCs after RARP [[11], [12], [13], [14]]. On average, the cutoff point in the literature for the extent of lymphadenectomy to increase the risk of SLCs is 10 lymph nodes, which is equal to the cutoff point where PLND is considered extended [14]. In our sample, all patients who presented SLCs had more than 10 lymph nodes removed; that is, they underwent extended PLND.
BMI has been reported as a predictor of SLCs in some studies in the literature, possibly due to the greater concentration of adipose tissue around the pelvic lymph nodes in obese men, and this tissue has inflammatory characteristics that can be triggered by the surgical procedure, contributing to the formation of SLCs [[11], [12], [13], [14], [15],17]. Although other studies have not shown a statistically significant impact of BMI on the development of SLCs after RARP with PLND [11,15,18], our results reinforce BMI as a predictor of SLCs. It is worth mentioning that most patients who developed SLCs postoperatively in our sample were, according to BMI, overweight or Grade I obesity.
Longer surgeon's time at the console or longer operating time, as well as longer hospital stay, may indicate more complicated surgery, which may lead to SLCs [13]. Although a previous study showed a significant relationship between operation time and SLCs [13], no study in the literature has shown an association between length of stay and SLCs, with our study being the first to place length of hospital stay as a risk factor for SLCs after RARP with PLND. Regarding the operation time, which in our sample was evaluated by the surgeon's time at the console, it was not statistically significant, possibly because it did not evaluate the entire procedure time.
Other risk factors for SLCs after robotic PLND reported in the literature are the high tumor grade, extracapsular extension, percentage of the gland affected by tumor, lymph node involvement, and prostate size [[11], [12], [13], [14], [15]]. In our analyses, none of these factors were associated with the presence of SLCs after RARP with PLND.
Finally, three recent meta-analyses have analyzed the peritoneal flap fixation technique in reducing the incidence of SLC formation and obtained good results, showing a statistically significant reduction in the incidence of SLCs in patients undergoing RARP with PLND with peritoneal flap fixation [[19], [20], [21]]. These findings, as well as the accumulated evidence on predictors of SLCs, indicate a solid perspective in preventing SLCs and decreasing its prevalence in cases of RARP with PLND.
This study has some limitations, the retrospective design and lack of analysis of the total operative time. Despite these limitations, this retrospective study presents significant volume of patients, which reinforces BMI and the number of lymph nodes removed as predictors of SLCs. All patients included in the study had a follow-up period of at least 6 months postoperatively, which is sufficient time to analyze this type of the complication according to the literature.
5. Conclusion
The prevalence of SLCs in patients undergoing RARP with PLND is approximately 2.0%. Higher BMI, greater number of lymph nodes removed, and longer length of stay are factors associated with the presence of SLCs.
Author contributions
Study concept and design: João P. Manzano, João H.S. de Pinho.
Data acquisition: João H.S. de Pinho, Thainã O. Azambuja, Davi S. Constantin.
Data analysis: João H.S. de Pinho, Vinicius M. de Souza.
Drafting of manuscript: João P. Manzano, João H.S. de Pinho, Thainã O. Azambuja, Davi S. Constantin, Vinicius M. de Souza.
Critical revision of the manuscript: João P. Manzano, João H.S. de Pinho, Thainã O. Azambuja, Davi S. Constantin, Vinicius M. de Souza.
Conflicts of interest
The authors declare no conflict of interest.
Footnotes
Peer review under responsibility of Tongji University.
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