Pelvic Lymphadenectomy in Prostate Cancer
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Prostate Cancer and Prostatic Diseases (2008) 11, 320–324 & 2008 Nature Publishing Group All rights reserved 1365-7852/08 $30.00 www.nature.com/pcan REVIEW Pelvic lymphadenectomy in prostate cancer BN Breyer1, KL Greene1, MA Dall’Era1, BJ Davies1 and CJ Kane2 1Department of Urology, University of California, San Francisco, CA, USA and 2Division of Urology, University of California, San Diego, CA, USA This review analyzes the anatomy of the prostate gland’s lymphatic drainage, the optimal anatomic extend of pelvic lymph node dissection (PLND) and which dissection may be superior, who should undergo a PLND during prostatectomy, and its potential therapeutic benefits and complications. The prostate gland’s lymphatic drainage can be variable, but frequently metastatic disease is found in the internal iliac chain. We conclude that the extended PLND yields the most lymph nodes and therefore may be superior. Some have demonstrated an unproven survival benefit after performing an extended PLND, possibly from removal of occult disease or from more accurate staging. Prostate Cancer and Prostatic Diseases (2008) 11, 320–324; doi:10.1038/pcan.2008.29; published online 20 May 2008 Keywords: pelvic lymph node dissection; lymph nodes; anatomy; radical retropubic prostatectomy The role of pelvic lymph node dissection (PLND) during they were relatively enlarged, whether they contained radical prostatectomy has generated considerable debate. cancer or not, compared to non-cancer cadavers. The central role of a PLND is to determine the Three approaches to the PLND have been described: locoregional extent of cancer, and to help evaluate the limited, standard and extended.8,9 (Table 1, Figure 1) need for adjuvant therapy and the risk of progression The exact nomenclature and surgical boundaries of and recurrence. Some believe that PLND is therapeutic PLND vary between institutions and lack standardiza- and promotes a cancer-specific survival benefit.1–4 tion. International consensus on anatomic boundaries This review aims to critically analyze: (1) the anatomy and use of descriptive terminology is needed.9 Standar- of the prostate gland’s lymphatic drainage, (2) the dization would promote uniformity of practice and anatomic boundaries of PLND and which dissection improve the comparison of future studies on PLND in may be superior, (3) who should undergo a PLND prostate cancer. during prostatectomy, (4) the potential therapeutic benefits of performing PLND and (5) the complications of PLND. What is the optimal anatomic extend of PLND? PLND anatomically defined Considerable debate exists over the appropriate bound- Anatomic studies have been performed to define the aries of PLND during radical retropubic prostatectomy periprostatic subcapsular lymphatic network that drains (RRP). Proponents of the extended PLND argue that it 5,6 significantly increases yield of both total LNs and LN the prostate. The network is composed of the ascend- 10,11 ing, lateral and posterior groups. The ascending ducts metastases. Heidenreich et al. compared a group drain into the external iliac lymph nodes, the lateral undergoing extended (n ¼ 103) vs standard (n ¼ 100) ducts into the hypogastric node chain, and the posterior PLND. In total 42% of all LN metastases were detected ducts draining from the caudal prostate to the subaortic outside the regions of the standard PLND and involved lymph nodes of the sacral promontory.5,6 the internal iliac and presacral regions. Nodal yield was Weingartner et al.7 performed extensive PLND on significantly higher (28 LNs vs 11 LNs), as was detection cadavers. A mean lymph node (LN) yield of 20 was of metastases (27 vs 12% of LN tissue) for extended found and the authors suggested that this number serve PLND and standard, respectively. Others have demon- as a guideline for sufficient PLDN. Interestingly, they strated a similar significant increase in LNs and analyzed prostate cancer patients’s LNs and found that metastasis yield after extended PLND compared to standard or limited PLND.2,12 Bader et al.13 provided further evidence that an extended PLND is needed to Correspondence: Dr CJ Kane, Division of Urology, University of provide adequate clinical staging and potential thera- California, San Diego, 200 W. Arbor Drive no. 8897, San Diego, CA peutic benefit. Men with clinically organ-confined 92103-8897, USA. E-mail: [email protected] prostate cancer underwent RRP and extended PLND, Received 24 March 2008; accepted 25 March 2008; published online and had their LNs prospectively evaluated for number 20 May 2008 and location of LN metastases. Of 365 patients, 88 (24%) Pelvic lymphadenectomy in prostate cancer BN Breyer et al 321 Table 1 Types of PLND for prostate cancer Types of PLND Lymph nodes Limited Obturator fossa lymph nodes Standard Obturator fossa and external iliac artery lymph nodes Extended Obturator fossa, external, internal and common iliac lymph nodes Abbreviation: PLND, pelvic lymph node dissection. Figure 1 Boundaries of extended lymph node dissection. Reprinted from Burkhard FC, Studer UE. The role of lymphadenectomy in prostate cancer. Urol Oncol 2004; 22: 198–202 (with permission from Elsevier). had positive LNs. Internal iliac LNs were positive for fully described. Berglund et al.19 found no difference in 5- metastasis and the solitary site in 58 and 19%, respec- year failure-free survival in patients who underwent tively. In their series, a PLND that spared the internal limited lymphadenectomy compared to those who did iliac bed would have left 58% of patients with positive not have the procedure. In addition, a higher rate of LNs with residual disease and 19% would have complications was associated with extended lymphade- been incorrectly staged as LN negative for cancer. nectomy. Similar findings were reported by Briganti et al.14,15 and Wawroschek et al.16,17 The total number of LNs removed during PLND is vital to ensure the accuracy of the staging procedure. As Who should undergo PLND? mentioned earlier, in cadaver studies, a mean LN yield of 20 was found to be sufficient. It has been demonstrated The primary function of PLND is to determine the local that the number of LNs dissected is directly associated extent of cancer, the risk of progression or recurrence and with an increased yield of metastatic LNs.2,10–12 the need for adjuvant therapy. In addition, a therapeutic In contrast, some argue that an extended PLND and cancer-specific survival benefit may occur after only causes increased morbidity and cost. Clark et al.18 PLND.1–4 With the rise of the prostate-specific antigen performed a prospective randomized study of 123 (PSA) era, a downward stage migration resulting from patients undergoing RRP with either limited (external the earlier detection of prostate cancer has led to a iliac and obturator fossa nodes) or extended (common decreased incidence of positive LNs.20–22 To determine iliac, internal iliac, external iliac, obturator fossa and who should undergo a PLND, the benefits must be presacral nodes) PLND. The randomization protocol weighed against the associated comorbidities and ap- assigned the extended dissection only unilaterally; on the plied to those who are at risk of metastatic disease. opposite side, a limited dissection was performed. They A number of nomograms have been developed to help concluded that extended PLND did not yield a substan- identify patients at risk for prostate cancer LN metastasis tially higher rate of positive nodes than the limited such as the Partin tables and the Kattan nomogram.22–26 dissection. Complications such as lymphocele or lower Based on these nomograms, patients who are considered extremity edema occurred more commonly in the low risk (preoperative PSA o10 ng/ml, a biopsy Gleason extended PLND. The study has been criticized because score (GS)o7, clinical stage ocT2b) often do not under- the numbers of subjects were too low for an equivalence go PLND during RRP because the likelihood of positive study; a unilateral focus of metastatic cancer would have LNs is less than 3%.23,25,27 been missed if it occurred on the side of the limited Although these tools provide guidance during clinical dissection; the majority of the patients had low meta- decision making, the methods behind generating them static risk; and the pathology review methods were not have several drawbacks. (1) They rely on historical Prostate Cancer and Prostatic Diseases Pelvic lymphadenectomy in prostate cancer BN Breyer et al 322 PLND studies with poorly defined dissection borders Are there therapeutic benefits to and in most cases are based on a limited PLND. (2) A performing PLND? documented trend toward higher Gleason grade assign- ments in contemporary patients may cause nomograms Controversy exists over the therapeutic benefits of PLND to underestimate metastatic risk.22–26,28 (3) Final RRP and whether it improves disease-specific and overall pathology is frequently downgraded or upgraded when survival. The landscape of prostate cancer treatment compared to preoperative biopsy specimen.29 Briganti continues to change as the PSA era promotes a stage et al.14,15 recently published a nomogram predicting the migration to lower risk disease. Multiple reports support probability of lymph node invasion among patients the contention that in patients with low-volume LN undergoing RRP and an extended PLND. This nomo- metastasis, PLND may have a therapeutic impact. Han gram is awaiting inter-institutional review and valida- et al.40 reported a 10% actuarial biochemical recurrence- tion. free rate 10 years after radical prostatectomy for patients A number of groups have demonstrated that the found to have lymph node micrometastases. Catalona likelihood of finding positive lymph nodes in patients et al.41 demonstrated a therapeutic benefit in a small with low-risk prostate cancer (preoperative PSA group of men (n ¼ 12) with positive LNs who received no o10 ng/ml, a biopsy Gleason score o7, clinical stage adjuvant therapy. The disease-free rate at 5 and 7 years ocT2b) is low.