Does Pelvic Lymph Node Dissection Improve the Biochemical Relapse-Free Survival in Low-Risk Prostate Cancer Patients Treated by Laparoscopic Radical Prostatectomy?

Abstract

Background and Purpose:

The roles and criteria for pelvic lymph node dissection (PLND) are not fully evaluated in patients with low-risk prostate cancer who are treated by laparoscopic radical prostatectomy (LRP). In this study, the outcome of PLND was assessed in terms of the biochemical relapse-free survival rates of low-risk prostate cancer patients who had undergone LRP.

Patients and Methods:

Included were 286 consecutive patients who were treated with LRP without previous endocrine therapy between 2002 and 2006 at our institution. Failure rates for LRP were compared in 139 patients with low-risk prostate cancer between those who underwent PLND (n=85) and those who did not (n=54). Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis.

Results:

The mean number of retrieved lymph nodes was 5.4±0.4 (range 2–22). The 5- and 7-year biochemical relapse-free survival rates were 90.1% and 88.3% in patients with PLND, and 82.4% and 82.4% in those without PLND (P=0.278), respectively (median follow-up 69.4 mos). None of the 85 patients undergoing PLND had positive lymph nodes. Only one patient had symptomatic lymphocele, and he was treated as an inpatient. The average time needed for PLND was 16 minutes, which corresponded to 7% of the entire operative time.

Conclusion:

These results indicate that the dissection of pelvic lymph nodes is not related to biochemical relapse-free survival. The omission of PLND in patients with low-risk prostate cancer not only does not adversely affect biochemical relapse-free survival, but might decrease the incidence of complication and operative time of LRP.

Introduction

D espite the development of radiologic imaging techniques, such as CT and MRI, pelvic lymph node dissection (PLND) represents the most accurate and reliable staging procedure for the detection of lymph node metastasis in prostate cancer today. In the era of prostate-specific antigens (PSA), the incidence of lymph node metastasis has declined, and PLND in prostatectomy is omitted in some cases.

None of the available guidelines recommend routine PLND staging in patients with low-risk prostate cancer.^1
–3 Nevertheless, the roles of PLND are still unknown, especially whether PLND might confer significant biochemical relapse-free survival benefit in low-risk prostate cancer. Furthermore, there are some reports of serious complications (lymphocele, leg edema, venous thromboembolism (VTE), etc.) of PLND in laparoscopic radical prostatectomy (LRP).^4,5

We report the impact of PLND in pure LRP on the outcome of patients with low-risk prostate cancer defined as Gleason score of 6 or less, PSA level of 10 ng/mL or less, and T stage of T_2a or less.¹

We assessed whether there are statistically significant differences in the biochemical relapse-free survival rates at 5 and 7 years after surgery in consecutive patients who were treated by LRP with and without PLND. Moreover, we analyzed the frequency of symptomatic complications after PLND and calculated the percentage of entire operative time needed for PLND.

Patients and Methods

Between January 2002 and December 2006, 286 consecutive patients without previous endocrine treatment underwent LRP at our institution. One hundred thirty-nine patients with serum PSA level <10 ng/mL, biopsy Gleason sum of 6 or less, and T stage of T_2a or less were identified and divided into two groups: Those who underwent PLND (PLND group, n=85) and those who did not (no-PLND group, n=54), as determined by the surgeon's discretion.

For the PLND group, the boundaries of dissection included the undersurface of the external iliac vein and obturator nerve, and lymph nodes were removed with all fatty, connective, and lymphatic tissues. These patients were followed by serum PSA value at 3-month intervals during the initial 2 years, every 6 months for the next 3 years, and then yearly thereafter.

Biochemical recurrence was defined as elevation of serum PSA level by >0.2 ng/mL. When serum PSA level did not reduce by >0.2 ng/mL, the first check of serum PSA level after LRP was conducted on the day of biochemical recurrence.

Biochemical relapse-free survival for each group was estimated by the Kaplan-Meier product-limit method. Mann-Whitney U test and chi-square test were used to estimate differences in clinical and pathologic data between the two cohorts. For all comparisons, a two-sided P value less than 0.05 was used to define statistical significance.

The symptomatic complications of PLND, whole operative times, and the required time for PLND were examined from the clinical record retrospectively, and the effectiveness of PLND was evaluated in patients with low-risk prostate cancer who were treated by LRP.

Results

The epidemiologic and clinical characteristics are summarized in Table 1, and pathologic characteristics are summarized in Table 2, stratified according to PLND status. No statistically significant differences were present between the groups. The median age of the 139 patients with low-risk prostate cancer as defined was 64.9 years (range 47–75 years), and the median preoperative serum PSA level and biopsy Gleason score was 6.4 ng/mL (range 3.6–9.9 ng/mL) and 5.2, respectively. None of the 85 patients who had undergone PLND had positive lymph nodes, and 67% of the patients had organ-confined disease. The mean of whole operative time was about 220 minutes in 85 patients who were treated by LRP with PLND, and the average time needed for PLND was about 16 minutes, which corresponded to 7% of the entire operative time. Only one patient had a symptomatic complication from PLND; he was treated for lymphocele as an inpatient. On the other hand, no patients who were treated without PLND in LRP had symptomatic complications.

Table 1.

Epidemiologic and Clinical Characteristics According to Pelvic Lymph Node Dissection

	Lymph node dissection
	Total	+	−	P value
No. of patients	139	85	54	0.606
Age	64.9	64.8	65.2	0.660
BMI	23.7	23.8	23.7	0.795
ASA-PS				0.606
1	71	45	26
2	68	40	28
MRI				0.250
T₁	39	27	12
T₂	100	58	42
PSA (ng/mL)	6.43	6.48	6.37	0.817
Gleason score (needle)	5.2	5.2	5.3	0.490
Positive core rate (%)	24	24	24	0.902

BMI=body mass index; ASA-PS=American Society of Anesthesiologists-physical status; MRI=magnetic resonance imaging; PSA-prostate-specific antigen.

Table 2.

Pathologic Characteristics According to Pelvic Lymph Node Dissection

	Lymph node dissection
	+	−	P value
Gleason score	5.87	6.09	0.186
Extracapsular extension			0.656
Absent	57	38
Present	28	16
Lymphovascular invasion			0.431
Absent	82	50
Present	3	4
Perineural invasion			0.554
Absent	62	42
Present	23	12
Seminal vesicle invasion			–
Absent	84	53
Present	1	1
Urethral invasion			–
Absent	84	54
Present	1	0

The median PSA follow-up time for the entire cohort was 69.4 months, with a similar follow-up for both cohorts (PLND group, 70.1 mos, and no-PLND group, 68.2 mos). Of all patients, biochemical relapse during follow-up developed in 18 (12.9%): 10 (18.5%) in the no-PLND group and 8 (9.4%) in the PLND group. The Kaplan-Meier estimates showed no differences in biochemical relapse-free survival between the two groups: The 5-year and 7-year biochemical relapse-free survival rates were 90.1% and 88.3% in patients with limited PLND, and 82.4 % and 82.4% in those without PLND (log-rank, P=0.278; Fig. 1).

FIG. 1.

Kaplan-Meier estimates of biochemical relapse-free survival rate according to pelvic lymph node dissection (PLND).

Discussion

Lymph node dissection as an adjunct of prostatectomy was thought to have some potential for therapeutic benefits. Bader and associates⁶ indicated that the number of lymphadenectomies might improve the time to progression. Joslyn and Konety⁷ showed that patients who underwent excision of at least 4 lymph nodes (both node-positive and node-negative patients) or greater than 10 nodes (only patients who were node-negative) had a lower risk of prostate cancer-specific death at 10 years than patients who did not undergo lymphadenectomy.

Moreover, in prostate cancer, precise staging is extremely important for the appropriate treatment and estimation of prognosis. The presence of lymph node metastasis in patients who had a diagnosis of clinically localized prostate cancer sometimes leads to an increase in the biochemical-recurrence rate after LRP.⁸ Accurate diagnosis in these patients allows more precise prognostication and may have important meaning to start adjuvant therapy.

Although the prevalence of pelvic lymph node metastases correlates directly with T stage, serum PSA level, and biopsy grade, and radiologic imaging techniques such as CT and MRI have been developed, PLND remains the most accurate staging modality for the detection of lymph node invasion in prostate cancer. In the era of PSA use, Partin and colleagues⁹ revealed that the incidence of lymph node metastasis has declined from rates of 20% to 40% in the 1970s and 1980s to less than 6% in the 1990s. As a result of this stage shift, PLND is omitted in some cases.

There have been no guidelines, however, regarding the area in which to perform PLND, the number of lymph nodes to be removed in prostatectomy, or that routinely recommend staging PLND in patients with low-risk prostate cancer. Nevertheless, it is still unknown whether PLND might confer significant biochemical relapse-free survival benefit in low-risk prostate cancer, because of the lack of prospective randomized trials. Few retrospective studies to date have assessed the impact of PLND on the outcome of low-risk patients who were treated with LRP. In the present study, we evaluated whether PLND is associated with biochemical relapse-free survival rate after LRP in patients with low-risk prostate cancer.

The results indicated that laparoscopic PLND in patients with low-risk prostate cancer did not improve biochemical relapse-free survival rate at 5 or 7 years after LRP. In some types of cancer—for example, bladder cancer¹⁰ and penile cancer¹¹—lymphadenectomy is an integral part of the surgical management, because dissection of involved lymph nodes improves survival. The therapeutic value of PLND in LRP remains a subject of intense debate. Weight and colleagues¹² showed that low-risk patients, with serum PSA level of 10 ng/mL or less, biopsy Gleason score of 6 or less, and clinical stage T₁ or T_2a, who were treated with open radical prostatectomy can be omitted from PLND, because the procedure does not affect biochemical relapse-free survival at 10 years, and the patients can be spared the morbidity and cost of PLND without affecting their chance for cure.

For the intermediate- and high-risk patients who were treated with LRP, extended PLND may improve their prognosis, because a study showed that extended PLND reduced the mortality rate by 23% if lymph nodes were positive and by 15% if they were negative.¹³ Heidenreich and coworkers¹⁴ estimated a 20% to 25% probability of detecting occult microscopic lymph node metastases in intermediate-risk patients by extended PLND, and a 30% to 40% probability in high-risk patients. On the other hand, in low-risk prostate cancer, only 1% to 3% of the patients with extended PLND in radical prostatectomy had nodal metastasis.^4,15 In Japanese men with a serum PSA level of 10 ng/m: or less, biopsy Gleason score of 6 or less, and clinical stage of T1c, T_2a, T_2b, or T_2c who underwent radical prostatectomy, 1% to 5% of the patients had lymph node involvement.¹⁶ In patients with low-risk prostate cancer, it appears to be beneficial to refrain from performing PLND.

Parkin and associates¹⁷ found, after laparoscopic PLND in patients with locally advanced prostate cancer, a major and minor complication rate of 5% and 17%, respectively. Complications in laparoscopic PLND were lymphocele, lower extremity edema, deep venous thrombosis, pelvic abscess, and ureteral injury, and the rates were 3.3%, 4.1%, 1.6%, 0.8%, and 0.8%, respectively; most of them appeared after performing extended PLND.¹⁸ VTE is the major mortality after radical prostatectomy. Eifler and colleagues⁵ showed that there was a significant association between VTE and LRP plus PLND compared with LRP only. They concluded that omitting PLND during LRP makes sense for patients at low risk for lymph node metastasis because of potentially catastrophic morbidity from VTE.

At our institution, only one patient needed admission to hospital for symptomatic lymphocele, which was a complication of PLND in LRP. This low rate of complications was a result of targeting PLND smaller than the areas targeted in other reports, and complications may not have been detected because CT or ultrasonography were not performed to detect lymphocele unless patients complained of the symptoms.

On the basis of an autopsy study, approximately 20 lymph nodes serve as a guideline for adequate and representative PLND.¹⁹ In the present study, PLND targeted the external iliac nodes and obturator fossa as sampling was performed, and the mean number of lymph nodes removed was 5.4±0.4. The area of PLND and the number of lymph nodes reserved are different in each institution, and comprise two of the limitations of this study.

Some other important limitations of this study are recognized. First, this study was retrospective, not randomized, comparing PLND in LRP to no-PLND for localized prostate cancer. Second, the mean follow-up in our series was 69.4 months. Further evaluation may be needed to confirm the long-term cancer-specific survival and metastatic progression rates.

The results of this study showed that PLND is not related to biochemical relapse-free survival. The omission of PLND in patients with serum PSA level <10 ng/mL, biopsy Gleason sum of 6 or less, and T stage of T_2a or less not only does not adversely affect biochemical relapse-free survival at 5 and 7 years after surgery, but also might decrease the incidence of complications and operative time of LRP. There has been no clear evidence that PLND offers any therapeutic benefit. As the incidence of positive nodes in low-risk disease is less than the complication rate, the utility of PLND in patients with low-risk prostate cancer needs further examination.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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