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Extended Lymph Node Dissection in Prostate Cancer: A Procedure With Therapeutic Utility

Extended Lymph Node Dissection in Prostate Cancer: A Procedure With Therapeutic Utility

Extended pelvic lymph node dissection (ePLND) represents the most accurate procedure for the detection of lymph node metastases in prostate cancer (PCa).[1] Although international guidelines suggest that ePLND should be performed whenever a lymph node dissection is indicated,[1,2] a disconcerting decrease in the utilization rates and extent of PLND in the contemporary era has been reported.[3] This may be mainly due to two factors: (1) increased operative time and potentially higher risk of perioperative complications associated with the procedure, and (2) lack of prospective, randomized evidence supporting the role of ePLND in cancer control. However, despite the lack of level 1 evidence, there are several oncologic benefits associated with ePLND, and these should always be considered when assessing the risk/benefit ratio of this procedure.

First, use of meticulous PLND in the identification of patients with lymph node invasion is not only important for staging but also for planning the optimal postoperative therapeutic approach.[4,5] Let us give an example. A patient with intermediate/high-risk PCa treated with radical prostatectomy (RP) and limited lymph node sampling is found to have pT3a, Gleason 4+4 PCa with negative surgical margins and 2 positive lymph nodes out of 4 removed. This patient has a detectable postoperative prostate-specific antigen (PSA) level of 0.5 ng/mL 8 weeks after surgery. In this case, one might postulate a persistence of nodal disease, given the inadequate extent of upfront PLND. However, the true nodal disease burden cannot actually be assessed in this case, since limited PLND equates to no PLND at all.[1] Conversely, if the same patient had the same pathologic characteristics and the same detectable postoperative PSA level but had a proper, anatomically defined ePLND (ie, 2 positive lymph nodes out of 28 removed), the probability of persistent pelvic nodal disease would be very much lower. This reduced likelihood of persistant pelvic nodal disease might have a significant impact on the determination of the optimal postoperative treatment. Indeed, even though the only relevant prospective randomized trial indicates that immediate hormonal therapy (HT) should be used in both cases,[4] we currently know that men with positive lymph nodes represent a highly heterogeneous patient population.[6-8] For this reason, the use of additional local therapies, such as pelvic radiotherapy (RT), may be considered beneficial in those node-positive patients more likely to have pelvic disease persistence/recurrence.[5] On the contrary, early salvage RT may not be indicated in patients who are more likely to have distant—rather than pelvic—disease recurrence. Similarly, individuals with a lower burden of nodal disease (ie, ≤ 2 positive nodes with microscopic involvement) and undetectable postoperative PSA might undergo expectant management and might be able to be spared immediate HT.[1,6,7] Key decisions such as this, regarding the optimal therapeutic process, are only possible if nodal status is accurately assessed by means of ePLND.

Second, previous studies have shown that up to 25% of patients with a low volume of nodal disease are free from even biochemical recurrence at long-term follow-up after RP and ePLND.[6] Although these data derive from retrospective observations, one can certainly postulate a beneficial effect of ePLND on cancer control in these men. Indeed, lymph node–positive PCa does not invariably represent a systemic disease and may benefit from proper local and pelvic control.[6-8] The latter can only be achieved by a properly performed ePLND.

Third, recent data have shown that more extensive PLND may directly improve disease control in node-negative patients, in addition to improving survival in men with node-positive PCa.[9-11] Unfortunately, the only prospective, randomized trial reporting a beneficial effect of ePLND on PCa control was retracted because of academic misconduct and data falsification.[8] Other future prospective randomized trials will need to fill this void. Having said this, it is certain that no trial will achieve any positive results if the two following prerequisites are not fulfilled: (1) Patients enrolled must have adequate life expectancy, and (2) they must be accurately selected. With regard to the removal of primary tumor in PCa, it is likely that those patients who stand to benefit the most from ePLND are younger men with more aggressive disease. Considering any other patient category would significantly dilute the effect of ePLND, as it does that of RP.

In conclusion, we maintain that ePLND should be offered to all PCa patients with an increased risk of lymph node invasion.[9] This procedure allows for proper nodal staging, optimal patient selection for additional cancer therapies, and improved cancer control in certain patients.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References

1. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol. 2014;65:124-37.

2. Mohler JL, Kantoff PW, Armstrong AJ, et al. Prostate cancer, version 2.2014. J Natl Compr Canc Netw. 2014;12:686-718.

3. Gandaglia G, Trinh QD, Hu JC, et al. The impact of robot-assisted radical prostatectomy on the use and extent of pelvic lymph node dissection in the “post-dissemination” period. Eur J Surg Oncol. 2014 Jan 02. [Epub ahead of print]

4. Messing EM, Manola J, Yao J, et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006;7:472-9.

5. Abdollah F, Karnes RJ, Suardi N, et al. Predicting survival of patients with node-positive prostate cancer following multimodal treatment. Eur Urol. 2014;65:554-62.

6. Briganti A, Karnes JR, Da Pozzo LF, et al. Two positive nodes represent a significant cut-off value for cancer specific survival in patients with node positive prostate cancer. A new proposal based on a two-institution experience on 703 consecutive N+ patients treated with radical prostatectomy, extended pelvic lymph node dissection and adjuvant therapy. Eur Urol. 2009;55:261-70.

7. Carlsson SV, Tafe LJ, Chade DC, et al. Pathological features of lymph node metastasis for predicting biochemical recurrence after radical prostatectomy for prostate cancer. J Urol. 2013;189:1314-8.

8. Ji J, Yuan H, Wang L, Hou J. Is the impact of the extent of lymphadenectomy in radical prostatectomy related to the disease risk? A single center prospective study. J Surg Res. 2012;178:779-84.

9. Briganti A, Larcher A, Abdollah F, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61:480-7.

 
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