Analysis of regional lymph nodes in periprostatic fat following robot-assisted radical prostatectomy

Authors


Bertram Yuh, Department of Urologic Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA. e-mail: byuh@coh.org

Abstract

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

A few publications have reported on the presence of lymph nodes in the anterior prostate lymphofatty tissue. This is important as increasing emphasis is placed on extending the overall limits of lymph node dissection in prostate cancer.

For a large group of patients treated with robotic prostatectomy we continue to routinely remove and examine this tissue in order to provide additional staging information for patients. In a comprehensive cancer centre, the long-term oncologic ramifications of excising tumour containing lymph nodes will continue to be studied.

OBJECTIVE

• To determine the incidence and significance of lymph nodes in the anterior prostatovesicular lymphofatty tissue.

PATIENTS AND METHODS

• One hundred and twenty patients with clinically localized prostate cancer underwent robot-assisted laparoscopic radical prostatectomy with excision of anterior prostatovesicular tissue at a single institution over a 6-month period.

• Tissue was sent for pathological analysis.

• Separate pelvic lymph node dissection was carried out in moderate-risk and high-risk patients.

RESULTS

• A total of 20 out of 120 patients (16.7%) had lymph nodes in the anterior lymphofatty tissue.

• Average lymph node number when present was 1.5 (one to three).

• Pathological assessment of the lymph nodes revealed metastatic prostate cancer in 3 out of 120 (2.5%) patients, each of whom had adverse pathological features.

• Patients with metastatic lymph nodes in the anterior tissue did not have cancer involvement of the pelvic lymph nodes.

• Patients with lymph nodes found in the anterior lymphofatty tissue were slightly younger but were otherwise similar with respect to other demographics, prostate-specific antigen, biopsy Gleason score, clinical stage, pathological stage, pathological Gleason score, seminal vesicle invasion, and margin status.

CONCLUSIONS

• Anterior lymphofatty tissue overlying the prostate occasionally contains lymph nodes that can harbour malignant disease and routine excision may eradicate regional tumour burden.

• Of patients with nodes, 15% were found to have malignant involvement.

• The long-term impact on progression-free and overall survival requires further study.

Abbreviation
ALFT

anterior lymphofatty tissue.

INTRODUCTION

The most reliable and definitive means of staging lymph node involvement in prostate cancer remains dissection and removal of the pelvic nodes. Recently, increased attention to extending the limits of obturator node dissection to include the external and internal iliac nodes has been suggested. Although consensus has not been reached regarding when and how to proceed, the current recommendation is that an extended pelvic lymph node dissection is preferred because it provides enhanced staging [1]. However, even with an extended dissection, landing zones for prostate cancer can still be missed.

During the anterior dissection of a radical prostatectomy, a shroud of lymphofatty tissue overlying the prostate that extends from the inner surface of the pubic bone towards the bladder is routinely encountered. This tissue is often excised to improve visualization and clearly expose the operative field. Robot-assisted laparoscopic pelvic lymph node dissection has been shown to be feasible with lymph node yields comparable to those for open dissection [2]. In addition, the three-dimensional magnification of the Da Vinci surgical robotic system (Sunnyvale, CA, USA) allows simple dissection of this fat away from the anterior prostate, apex, endopelvic fascia and bladder neck.

We commonly perform excision of this tissue with pathological analysis because others have described the occasional presence of lymph nodes [3,4]. We surmised that regional lymph node removal could provide better oncological staging and define patients at greater risk for disease recurrence. Over a 6-month period we prospectively examined the incidence of nodal tissue in the anterior lymphofatty tissue (ALFT) specimen and examined clinical and pathological predictors of malignancy in these lymph nodes.

METHODS

Over a 6-month period between January and June 2010, 120 patients undergoing robot-assisted laparoscopic radical prostatectomy at the City of Hope National Cancer Center were entered onto the City of Hope Prostate Cancer Database and enrolled in our institutional review board-approved study. Patients had a preoperative bone scan and computed tomography of the abdomen and pelvis as clinically indicated. All patients had their ALFT sent for pathological analysis. Standard template pelvic lymph node dissection of the obturator fossa and internal and external iliac chains was carried out in medium-risk and high-risk patients (Gleason score ≥7, PSA >10, or cT2b or above) and in selected low-risk patients according to D’Amico risk criteria. Database records were reviewed for demographic information, pathology and operative data.

Technical aspects of tissue removal are as follows. After posterior dissection and release of the bladder from the anterior abdominal wall, the retropubic space is developed. The pubic arch is identified and the lymphofatty tissue overlying the prostate, bladder neck and endopelvic fascia is dissected free starting from the inner surface of the pubic arch. The lateral edges of the prostate are maintained as the lateral borders of dissection to maintain integrity of the pelvic sidewall lymphatic tissue. The tissue is kept on traction and easily mobilized away with minimal cautery and removed en bloc through the assistant port. We then perform bladder neck dissection through the perivesical space, which is facilitated by the removal of the previous tissue. The entirety of this dissection is performed before pelvic lymph node dissection and is anatomically separate from the pelvic sidewall.

All prostatectomy specimens with corresponding pelvic lymph nodes and ALFT from these patients were submitted routinely for processing and examination in the pathology department after surgery. Specifically for each ALFT specimen, all possible lymph nodes and the entire fatty tissue specimen were fixed in formalin, embedded in paraffin tissue blocks, and underwent standard pathological assessment for lymph nodes by a single pathologist. No special methods were employed.

Data analysis was performed using a standard statistical package (SAS®; SAS Institute, Cary, NC, USA). Data were summarized using descriptive statistics. A two-sided Student’s t test was used to test for differences in continuous data, and a chi-squared test for equality was used to compare proportions for categorical data.

RESULTS

A total of 120 patients had specimens sent from the ALFT for pathology permanent section. Dissection of the ALFT did not result in any intraoperative or postoperative morbidity and did not affect operative time. The ALFT specimen size varied greatly but ranged between 1 and 6 cm in length and did not correlate with prostate size. In all, 64 of 120 (53%) patients underwent standard pelvic lymphadenectomy with a mean yield of 7.7 lymph nodes (range 2–25). Table 1 lists demographic data comparing patients with and without lymph nodes found in the ALFT. Patients with ALFT lymph nodes were slightly younger, with a median age of 60.5 years compared with a median age of 65.0 years in patients without ALFT lymph nodes (P= 0.02). There were no differences in ethnicity, body mass index, PSA, biopsy Gleason score, clinical stage, pathological stage, pathological Gleason score, seminal vesicle invasion, or margin status between groups.

Table 1.  Demographics comparing patients with lymph nodes present or absent in anterior lymphofatty tissue (ALFT)
 Lymph nodes present in ALFT (n= 20)Lymph nodes absent in ALFT (n= 100)P value
Age at surgery, median (sd)60.5 (6.4)65.0 (7.3)0.02
Race, n (%)   
 Caucasian17 (85.0)85 (85.0)0.38
 Black 1 (5.0) 7 (7.0) 
 Asian 0 (0.0) 5 (5.0) 
 Other 2 (10.0) 3 (3.0) 
BMI, mean (sd)28.4 (4.0)28.0 (5.1)0.73
Prostate weight, mean (sd)57.0 (16.5)53.1 (16.7)0.34
PSA, n (%)   
 0–3.9 3 (15.0)20 (20.0)0.91
 4–1015 (75.0)69 (69.0) 
 >10 2 (10.0) 11 (11.0) 
Preoperative Gleason Score, n (%)   
 2–6 7 (35.0)43 (43.0)0.80
 7 11 (55.0)48 (48.0) 
 8–10 2 (10.0) 9 (9.0) 
Clinical T stage, n (%)   
 T1abc13 (65.0)78 (78.0)0.30
 T2/T2a/T2b 7 (35.0)20 (20.0) 
 T2c 0 (0.0) 2 (2.0) 

Table 2 lists the surgical and pathological data from the patients with and without ALFT lymph nodes. Twenty of the 120 (16.7%) patients had lymph nodes in their surgical specimens. In these patients, the number of nodes ranged from one to three (mean 1.5). Lymph node size ranged from 0.3 to 1.5 cm and did not correlate with malignancy, there were both benign and malignant lymph nodes measuring 1.5 cm. Size of tumour deposit in the lymph nodes ranged from 0.1 to 0.7 mm.

Table 2.  Surgical and pathologic data comparing patients with lymph nodes present or absent in anterior lymphofatty tissue (ALFT)
 Lymph nodes present in ALFT (n= 20)Lymph nodes absent in ALFT (n= 100)P value
Intraoperative blood loss, mean (sd)208.6 (123.1)201.4 (108.6)0.79
Pathological T stage, n (%)   
 pT2 14 (70.0) 75 (75.0)0.15
 pT3  5 (25.0) 24 (24.0) 
 Indeterminate  1 (5.0)  1 (5.0) 
Seminal vesicle invasion, n (%)   
 Negative 19 (95.0) 89 (89.0)0.41
 Positive  1 (5.0)  11 (11.0) 
Surgical Gleason Score, n (%)   
 ≤6  5 (25.0) 17 (17.0)0.80
 7 12 (60.0) 71 (71.0) 
 8–10  2 (10.0)  8 (8.0) 
 Indeterminate  1 (5.0)  4 (4.0) 
Surgical margin status, n (%)   
 Negative 16 (80.0) 74 (74.0)0.57
 Positive  4 (20.0) 26 (26.0) 

Three of the 20 patients with ALFT lymph nodes had metastatic prostate cancer in the ALFT (Fig. 1), in one lymph node for each patient. None of these patients with positive ALFT lymph nodes had positive pelvic sidewall lymph nodes. All of these patients showed some component of carcinoma in the anterior prostate. Intraoperative findings were not predictive of metastatic cancer in this tissue. Clinical data for these patients are listed in Table 3. Of the three patients with positive lymph nodes, two had undetectable PSA at follow-up (8 months). The third patient had an elevated PSA of 7.8 and subsequently was placed on combined androgen blockade and a clinical trial of taxotere-based chemotherapy.

Figure 1.

Lymph node infiltrated by metastatic prostate cancer.

Table 3.  Patients with positive lymph nodes in anterior lymphofatty tissue (ALFT)
 Age (year)LN + ve/LN foundFinal Gleason gradePathological stage% involvement of tumourSurgical marginsPelvic LN +ve/ total pelvic LNPreop. PSAPreop. CTPreop. stageBiopsy Gleason Grade
1.601/14 + 3pT3a90/98.87negativeT1c3 + 4
2.701/23 + 4pT3a36+0/57.4n/aT1c3 + 4
3.701/14 + 5pT2c100/414negativeT24 + 5

DISCUSSION

Survival of patients with prostate cancer is adversely affected by lymph node metastasis, with involvement of the lymph nodes signifying more advanced disease. For patients undergoing surgical excision as definitive treatment, accurate staging is important to identify patients who are at risk for disease progression. Pelvic lymph node dissection remains the standard for staging nodal involvement. While ALFT lymph nodes are found only in a minority of patients, the nodes may have a relatively high rate of malignancy (in three of 20 patients).

Brössner et al. [5] previously established a framework of anatomical drainage of the prostate using injection of contrast medium into the prostate followed by serial imaging. For all patients studied, prostatic drainage involved three major routes, primarily to the lateral pelvic wall to the internal/external iliac group to the common iliac group; to the perineal floor to the internal pudendal lymph nodes to the iliac groups; and to the sacral lymph nodes. None of the patients with positive periprostatic nodes also had positive pelvic sidewall lymph nodes in our study, suggesting that in some patients, it may represent a pre-lateral pelvic wall landing zone. A previous study is similar in showing that three out of four patients with positive ALFT had negative pelvic sidewall nodes [4].

The predominant lymphatic drainage of the prostate is to the obturator fossa and surrounding the external and internal iliac vessels [6]. However, a substantial percentage of lymphatic drainage from the prostate is to other lymphatic drainage basins [7]. Schilling et al. [8] used Tc-99m-labelled nanocolloid prostatic injection for targeted lymph node dissection using a gamma-probe and found 51.6% of lymph node metastases to be outside the obturator fossa. Similarly, Mattei et al. [9] used injection with post-injection single photon emission computed tomography (SPECT) CT/MRI showing coverage of two-thirds of primary prostatic lymphatic landing sites with an extended pelvic lymph node dissection compared with only one-third in a limited pelvic lymph node dissection.

When pelvic lymph node dissection is performed, the rate of malignant involvement increases with more aggressive dissection [1,10,11]. Extending the boundaries of dissection increases lymph node yield, allowing better staging [12] without generally affecting complication rates [13]. Frequently, when this tissue is encountered intraoperatively it is cauterized or discarded, precluding pathological assessment. For most patients this is likely to be of no consequence; however, occasional patients have tumour involvement of these lymph nodes, which increases the pathological stage to N1 [4].

No universal agreement regarding the optimal dissection for prostatectomy patients has been reached, so the decision should be patient-specific on a case-by-case basis. In certain circumstances, omitting pelvic lymph node dissection in low-risk patients can be considered [14]. The decision-making process and discussion with patients before embarking on surgery depends on currently identifiable criteria (PSA, disease stage and tumour grade [15]) and also on not presently identifiable criteria.

Despite advancements in imaging technology, staging of lymph nodes through imaging modalities alone remains suboptimal. For CT and MRI, the sensitivity and specificity for detecting lymph node metastases is approximately 0.4 and 0.8, respectively [16]. More recent investigations combining ultrasmall superparamagnetic iron particles and diffusion-weighted MRI have accurately detected 92% of cancerous lymph nodes [17]. Nevertheless, some cases of micrometastatic disease are still overlooked, though the clinical significance of this is uncertain.

Finley et al. as well as others [3,4] have previously described the presence of lymph nodes in the periprostatic and perivesical tissue. The described nodal detection rates and nodal malignancy rates are between 4.4 and 14.7% and between 0.6 and 2%, respectively. Similarly, our nodal detection rate was 16.7% with 2.5% metastatic detection. All patients with positive nodes in these studies had disease of pT3 and above but one of the patients in our study had pT2c disease (although with Gleason 9 cancer), suggesting that ALFT involvement is possible even in organ-confined disease.

Extended pelvic lymph node dissection for invasive transitional cell carcinoma of the bladder has established its importance in staging as well as in improving survival [18]. Bladder and prostate cancers often drain through similar lymphatic channels and some comparisons may be made. Involvement of perivesical lymph nodes is occasionally seen in bladder cancer. Metastatic transitional cell carcinoma in these nodes is associated with significantly worse overall and disease-specific survival [19]. Most patients (10/14) with perivesical lymph node involvement did not have metastatic disease in the pelvic nodes but mean overall survival was only 6 months. It also appears that patients with prostate cancer and positive ALFT nodes generally do not have metastatic disease in the pelvic nodes. Though the long-term benefit of extended pelvic lymph node dissection is debatable for prostate adenocarcinoma, the recent body of literature suggests a possible improvement in biochemical relapse even in node-negative patients [20]. Patients in this study who underwent lymph node dissection removing less than 10 nodes had a significantly higher biochemical relapse rate compared with those with removal of 10 or more nodes.

Gross examination of the ALFT generally failed to show the presence of lymph nodes. However, on further microscopic examination about 16% of specimens contained lymph nodes and 2.5% showed metastatic prostate cancer. The use of microscopy may explain the higher occurrence of lymph nodes found in the present study compared with a previous study that screened specimens based on examination with the naked eye [4]. Hence, it may be beneficial to microscopically examine all ALFT specimens regardless of their gross appearance.

At the time of prostatectomy, we routinely proceed with a pelvic lymph node dissection for improved staging confidence and remove the ALFT because it helps to visually guide our entry point for bladder neck dissection, provides better depiction of anatomical relations and assists with apical dissection of the prostate. If not removed this tissue could represent a troublesome site of detectable PSA after prostatectomy or nidus for malignant persistence. In our series of patients with evidence of pathological adenocarcinoma in the ALFT, the clinical course of these patients was variable. Although they all had adverse pathological characteristics, only the patient with Gleason 4 + 3, pT3a disease had an elevated PSA postoperatively and was subsequently placed on systemic therapy. The other two patients, though with high-risk cancer characteristics (one patient with pT3a and positive margins and another with Gleason 4 + 5 disease) have had no biochemical evidence of recurrence.

Generally, patients with low-volume nodal metastases experience very good overall survival [1]. As such, this subgroup of patients with a solitary metastatic node may experience similar survival. The role of adjuvant therapy is unclear. Whether or not these patients would benefit more from pelvic radiation than those N1 patients with pelvic sidewall involvement requires further examination. Patients with anteriorly detected prostate cancer may be more at risk for positive ALFT lymph nodes.

The limitations of this study are the small number of lymph-node-positive patients and short follow-up. The phenomenon of lymph nodes in the ALFT is an uncommon entity and more study is required. With more patients the natural course may be elucidated. Longer follow-up will be needed on these patients to fully ascertain the effect of these lymph nodes on survival. Additionally, while strict adherence to a template excision as described above was followed, the boundaries of ALFT are somewhat indiscrete and variable.

CONCLUSION

Lymph nodes are occasionally found by microscopic examination of lymphofatty tissue anterior to the prostate and may contain regional spread of prostate cancer. This tissue may represent a preliminary landing site in a minority of prostate cancer patients. The long-term status and ramifications of detection and excision need to be determined.

ACKNOWLEDGEMENTS

The authors would like to thank Nicola Solomon for editorial assistance and critical review of the manuscript.

CONFLICT OF INTEREST

Timothy Wilson is a speaker to Astellas and Intuitive Surgical.

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