UROLOGY ANZJSurg.com
Extended pelvic lymph node dissection for clinically localized prostate cancer: a West Australian experience Alarick Picardo and Justin Vivian Urology Department, St John of God Hospital, Perth, Western Australia, Australia
Key words lymph node dissection, radical prostatectomy, robotic. Correspondence Dr Alarick Picardo, Urology Department, St John of God Hospital, 12 Salvado Road, Subiaco, WA 6008, Australia. Email: [email protected] A. Picardo MBBS; J. Vivian FRACS (Urology). The early results were presented at the WA section meeting of USANZ in 2011. Accepted for publication 21 January 2015. doi: 10.1111/ans.13035
Abstract Background: The role and type of pelvic lymph node dissection for clinically localized prostate cancer is controversial in Australia. Our study aims to determine the incidence of pelvic lymph node involvement and the complication rate of extended lymphadenectomy in a group of West Australian patients who underwent a robotic assisted radical prostatectomy plus extended pelvic lymph node dissection. Method: Forty-nine patients underwent a robotic assisted radical prostatectomy with extended pelvic lymph node dissection between 2008 and 2012 by a single private urological surgeon. The inclusion criteria for the extended lymph node dissection were clinical localized, intermediate and high-risk prostate cancer based on preoperative D’Amico classification. Results: Of the 49 patients, eight patients had positive nodes giving a nodal positivity rate of 16.33%. Six patients had a complication giving a total complication rate of 12.24%. Three of these complications have been attributed to the nodal dissection, thus giving an extended pelvic lymph node dissection complication rate of 6.12%. Conclusion: Rates of nodal involvement in our West Australian cohort are in keeping with those published in the literature. Extended pelvic lymph node dissection can be performed with an acceptable complication rate. Further research is required to investigate the therapeutic role of pelvic lymph node dissection.
Introduction The role of pelvic lymph node dissection in the treatment of prostate cancer is controversial. In Australia, there are no national guidelines on whom to perform a nodal dissection. There are international organizations such as the American Urological Association, National Clinical Cancer Network and European Urological Association that have guidelines pertaining to this subject. Unfortunately, these recommendations and guidelines conflict with one another making clinical decisions more difficult. To our knowledge, in Western Australia, an extended pelvic lymph node dissection is not commonly performed with radical prostatectomy, especially for intermediate-risk disease. This contrasts to the recommendations of international urological organizations, listed in Table 1,1–3 that suggest using nomograms to stratify patients according to the risk of lymph node involvement. Importantly, these guidelines were based on nomograms aimed at predicting the presence of lymph node involvement from limited or standard nodal dissections, and subsequently, the true incidence of nodal involvement may be higher than expected. More recently, Briganti et al. have published their nomogram for predicting lymph ANZ J Surg 85 (2015) 936–940
node involvement based on patients who have an extended pelvic nodal dissection.4 Our study reports the incidence of nodal involvement and the complication rate of extended nodal dissection in a group of Western Australian patients with clinically localized, intermediate to highrisk prostate cancer.
Methods Patient population Between June 2008 and June 2012, 49 patients underwent a robotic assisted radical prostatectomy with an extended pelvic lymph node dissection by a single urologist in Western Australia. Inclusion criteria to be offered this treatment were an intermediate or high D’Amico score.5 Table 2 lists baseline patient characteristics.
Surgical technique Patients underwent a robotic assisted extended pelvic lymph node dissection similar to that described by Feicke et al.6 Of note, the © 2015 Royal Australasian College of Surgeons
ePLND for prostate cancer
937
external iliac nodes, obturator nodes and internal iliac nodes were removed; however, presacral lymph nodes described by some authors as part of an extended pelvic lymph node dissection (ePLND) were not removed.
Results A median of 17 (average 17.7, standard deviation 6.1) nodes were removed per patient. Eight patients had positive lymph nodes giving Table 1 Pelvic lymph node dissection recommendations from major urological organizations Organization
Recommendation
EAU
Extended pelvic lymph node dissection should be performed in intermediate-risk, localized PCa if the estimated risk for positive lymph nodes exceeds 5%, as well as in high-risk cases. Pelvic lymph node dissection is generally reserved for patients with higher risk of nodal involvement Extended pelvic lymph node dissection for patients with >2% predicted probability of nodal metastases
AUA NCCN
AUA, American Urological Association; EAU, European Association of Urology; NCCN, National Cancer Council Network; PCa, prostate cancer.
a nodal positivity rate of 16.3%. Table 3 shows the characteristics of all lymph node-positive patients. Five patients, all with positive lymph nodes, had biochemical failure, defined as a detectable, rising post-operative prostate-specific antigen (PSA). Four of these patients were commenced on androgen deprivation therapy and one received adjuvant radiotherapy as surgical margins were positive. The other three patients with positive lymph nodes remain under close surveillance for biochemical recurrence. The average additional operative time required for the extended nodal dissection was 45.7 min. Complications were graded according to the modified Clavien classification7 as seen in Table 4. Overall complication rate for radical robotic assisted prostatectomy with extended pelvic lymph node dissection was 12.2%.
Discussion This study shows rates of lymphatic metastases in Australian men undergoing this staging procedure are similar to those presented in the international literature. Complication rates are also similar to those reported previously. Pelvic lymph node dissection in localized prostate cancer is a controversial topic because of a lack of randomized controlled trials
Table 2 Baseline patient characteristics Number of patients Median age, year (range) Median PSA, ng/mL (range) Biopsy Gleason score, no. (%) 3+4=7 4+3=7 4+4=8 4+5=9 Clinical stage, no. (%) cT1c cT2a cT2b cT2c cT3 Percentage positive cores on biopsy, no. (%) ≤25% 25–≤50% 50–≤75% >75%
Total 49
LN+ 8
LN− 41
63 (45–74) 7.6 (3.3–56.8)
65 (55–74) 11.15 (7.3–56.8)
63 (45–73) 7.4 (3.3–13.8)
14 (28.5%) 23 (46.9%) 9 (18.4%) 3 (6.1%)
1 (12.5%) 2 (25.0%) 3 (37.5%) 2 (25.0%)
13 (31.5%) 21 (51.2%) 6 (14.6%) 1 (2.4%)
21 (42.9%) 12 (24.5%) 9 (18.4%) 6 (12.2%) 1 (2.0%)
1 (12.5%) 1 (12.5%) 3 (37.5%) 2 (25.0%) 1 (12.5%)
20 (48.9%) 11 (26.8%) 6 (14.6%) 4 (9.8%) 0 (0%)
12 (25%) 10 (20.8%) 10 (20.8%) 16 (33.3%)
1 (12.5%) 2 (25.0%) 0 (0.0%) 5 (62.5%)
11 (26.8%) 8 (19.5%) 10 (24.4%) 11 (26.8%)
PSA, prostate-specific antigen.
Table 3 Node-positive patients Patient
1 2 3 4 5 6 7 8
Biopsy Gleason score 4 4 3 4 4 4 4 4
+ + + + + + + +
3 3 4 5 5 4 4 4
= = = = = = = =
7 7 7 9 9 8 8 8
Pathologic Gleason score 4 4 3 4 5 4 4 4
+ + + + + + + +
3 3 4 5 4 3 4 3
= = = = = = = =
7 7 7 9 9 7 8 7
PSA, prostate-specific antigen.
© 2015 Royal Australasian College of Surgeons
Clinical stage
Pathological Stage
PSA
Surgical Margin
Tumour volume (mL)
Proportion nodes positive
Biochemical recurrence
cT3 cT2a cT1c cT2c cT2b cT2b cT2b cT2c
pT3a pT3a pT3a pT3b pT3b pT3b pT3b pT3a
7.3 12.3 13 9.5 10 56.8 9.9 20
Negative Negative Negative Positive Negative Positive Positive Negative
8.03 12.2 10.3 31.8 9.4 14.1 21.2 6.6
3/16 4/26 1/11 3/18 1/20 1/18 2/10 4/14
Yes No No Yes Yes Yes No Yes
938
Picardo and Vivian
Table 4 Complications following radical prostatectomy and ePLND as per Clavien Dindo classification Number of complications Grade I
2
Grade II Grade III Grade IV
0 1 3
Total
6
Types of complications (number of patients)
Percentage of total
Ileus (1) Anastomotic leak (1)
2/49 = 4.1%
Incisional hernia (1) Pulmonary embolism (1) Septicaemia secondary to infected lymphocele (2)
1/49 = 2.0% 3/49 = 6.1%
6/49 = 12.2%
to explore the risk benefit equation. Additionally, there are discrepancies in the literature regarding definitions, indications and benefits. Currently, there are three types of lymph node dissections performed in conjunction with a radical prostatectomy – limited, standard or extended. While it is generally accepted that a limited nodal dissection removes the obturator package and the standard dissection additionally involves dissection of the external iliac nodes, there is no standardization or universally accepted operative template regarding the extended lymph node dissection. In these situations, often, urologists will dissect the obturator, external iliac, hypogastric (internal iliac) and common iliac nodes; however, additional nodes in presacral, paraaortic, pararectal and paravesical regions can be involved and dissected as illustrated in lymphoscintigraphic studies of the prostate.8–10 These studies have confirmed the lymphatic drainage of the prostate to be unique and that different nodal groups can be affected independently of each other with authors reporting that up to 40% of lymph nodal involvement (LNI) can be missed with a limited node dissection alone.11,12 This variability in the extended dissection template makes it difficult to compare results with documented average nodal yields for an ePLND ranging from 11.6 to 28.6,12,13 Our study with its mean and median nodal yield of 17.7 and 17.0, respectively, is consistent with the average reported in the literature. Additionally, our nodal positivity rate of 16.3% and the nodal positivity as a percentage of tumour stage and Gleason grade is in keeping with those published in the international literature.6,14 Interestingly, our nodal positivity yield is significantly higher than that published by Sengupta et al., which is to our knowledge the only other publication on pelvic lymph node dissection for prostate cancer in Australia.15 In their retrospective analysis, 200 men underwent a radical prostatectomy plus lymph node dissection involving the obturator package and anterior half of the internal iliac package (median nodal yield of 2), with lymph node metastases reported in 10 patients (5%). We believe our higher nodal positivity rate is due to excluding patient’s with low-risk prostate cancer (according to D’Amico classification) and by reducing understaging through performing an extended nodal dissection. Complications from pelvic lymph node dissection have been reported at rates ranging from 5% to over 35%.16–19 The most common complications are lymphoceles, thromboembolic complications, neurologic injury, ureteric injury or vascular injuries. The complication rate for an ePLND is higher than that of a limited or standard dissection, with many authors showing particularly higher
rates of lymphocele formation.17 In our study, two patients developed sepsis secondary to an infected lymphocele and another developed a pulmonary embolism secondary to deep vein thrombosis. Other minor complications encountered were a post-operative ileus, an incisional hernia and an anastomotic leak, all managed conservatively. The total complication rate was 12.2%, which is well within the accepted range for a radical prostatectomy and node dissection. Furthermore, if we attribute the lymphoceles and thromboembolic complications to the lymphadenectomy, then the complication rate for the extended pelvic lymph node dissection is only 6.1%. While this is reasonably low, it is important to remember that these complications were Clavien class III or IV complications (potentially life threatening requiring intensive care management) and although all patients had good final outcomes, it is important to always consider the mortality and morbidity of this additional procedure and weigh it against its benefits. This is the critical question with pelvic lymph node dissection and in general, there are two main reasons why a pelvic node dissection is advocated. Firstly, knowing if there are lymphatic metastases provides better prognostic information. Secondly, there is a proposed therapeutic benefit.20,21 While new imaging and nuclear medicine techniques are being investigated, currently, a PLND is the only available technique that accurately determines nodal status that then provides information on prognosis. Patients with nodal metastases have a significantly poorer outcome as shown in a large population-based study where the 5-year cancer-specific mortality in nodal negative T2 patients is 3.9% compared with 20.6% in node-positive patients.22 Additionally, many authors have reported that the number of positive nodes or positive nodal density is proportional to the risk of biochemical failure.21,23,24 Knowing nodal status may influence the decision to use adjuvant androgen deprivation treatment, which has been shown to be beneficial.22 It may encourage closer monitoring for biochemical failure.25,26 In high-risk patients, or those who do not achieve biochemical cure, it may also influence the decision to use adjuvant or salvage radiotherapy.27 Several studies report a potential therapeutic benefit for an extended lymphadenectomy. They report improved cancer-specific survival and reduced biochemical recurrence in patients who undergo a pelvic lymph node dissection, even in nodal negative patients.21,28,29 It is suggested that this therapeutic effect is due to the removal of occult micrometastatic disease and there is some evidence to support this explanation. Using immunohistochemistry, Pagliarulo et al. re-reviewed 3914 nodes from 180 N0 patients and found occult tumour cells present in the nodes of 24 patients (13.3%).30 This finding indicates the incidence of true lymph node involvement is higher than reported. Despite this being an adequate explanation for those studies that show improved outcomes, other papers have failed to show any survival benefit following lymphadenectomy or therapeutic benefits of extended over limited dissections.31–33 Furthermore, Abdollah et al. has shown in his population-based study using the Surveillance, Epidemiology and End Results (SEER) registry that while patients treated with prostatectomy without nodal dissection (pNx) have a less favourable survival © 2015 Royal Australasian College of Surgeons
ePLND for prostate cancer
rate than patients who have a nodal dissection and are truly node negative (pN0), the difference is very modest (0.8% at 10 years).22 The author had performed 50 robotic assisted radical prostatectomies before starting performing extended lymph node dissections. The median additional time for performing this surgery was 46 min but in the initial experience, it was approximately 90 min. The average total theatre time for these procedures was 303 min. Increased length of procedural time has been associated with increased complication rates though this was not observed in this study. In the authors’ opinion, the rationale for performing an extended pelvic lymph node dissection in high-risk prostate cancer justifies the risk as the additional information obtained helps guide subsequent decision making. In intermediate-risk disease, where the rate of node positivity is less, treatment should be individualized by counselling patients regarding the potential risks and benefits of this additional procedure. This would be an ideal subject for a treatment study, either randomized controlled or a prospective cohort trial.
Conclusion The role of pelvic lymph node dissection in the treatment of localized prostate cancer will remain a controversial issue until further studies validate its proposed therapeutic benefit. If a dissection is to be performed, the most value will be obtained from an extended pelvic lymph node dissection, which can be performed with an acceptable complication rate. Further research is essential to investigate the therapeutic benefits of a lymph node dissection as well as adjuvant therapies for patients with nodal involvement.
References 1. NCCN Clinical Practice Guidelines in Oncology – Prostate Cancer. 2013. [Cited 20 May 2013.] Available from URL: http://www.nccn.org/ professionals/physician_gls/pdf/prostate.pdf. Ver 2. 2. American Urological Association. Guideline for the Management of Clinically Localized Prostate Cancer. 2007. [Cited 16 Jan 2012.] Available from URL: http://www.auanet.org/common/pdf/education/ clinical-guidance/Prostate-Cancer.pdf 3. European Association of Urology. Guidelines on Prostate Cancer. 2011 [Cited 16 Jan 2012.] Available from URL: http://www.uroweb.org/gls/ pdf/08_Prostate_Cancer%20September%2022nd%202011.pdf 4. 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. 5. D’Amico AV, Whittington R, Malkowicz SB et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280: 969–74. 6. Feicke A, Baumgartner M, Talimi S et al. Robotic-assisted laparoscopic extended pelvic lymph node dissection for prostate cancer: surgical technique and experience with the first 99 cases. Eur. Urol. 2009; 55: 876–83. 7. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 2004; 240: 205–13. 8. de Bonilla-Damia A, Roberto Brouwer O, Meinhardt W, Valdes-Olmos RA. Lymphatic drainage in prostate carcinoma assessed by
© 2015 Royal Australasian College of Surgeons
939
9. 10.
11.
12.
13.
14.
15.
16.
17. 18. 19.
20.
21.
22.
23.
24.
25.
26.
lymphoscintigraphy and SPECT/CT: its importance for the sentinel node procedure. Revista espanola de medicina nuclear e imagen molecular 2012; 31: 66–70. Cellini N, Luzi S, Mantini G et al. Lymphatic drainage and CTV in carcinoma of the prostate. Rays 2003; 28: 337–41. Jeschke S, Burkhard FC, Thurairaja R, Dhar N, Studer UE. Extended lymph node dissection for prostate cancer. Curr. Urol. Rep. 2008; 9: 237–42. Heesakkers RA, Jager GJ, Hovels AM et al. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging. Radiology 2009; 251: 408–14. Heidenreich A, Varga Z, Von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J. Urol. 2002; 167: 1681–6. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J. Urol. 2004; 172 (5 Pt 1): 1840–4. Wyler SF, Sulser T, Seifert HH et al. Laparoscopic extended pelvic lymph node dissection for high-risk prostate cancer. Urology 2006; 68: 883–7. Sengupta S, Weerakoon M, Sethi K, Ischia J, Webb DR. Algorithm for selecting men for pelvic lymph node dissection (PLND) during radical prostatectomy based on clinical risk factors in an Australian population. BJU Int. 2012; 109 (Suppl. 3): 48–51. Briganti A, Chun FK, Salonia A et al. Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur. Urol. 2006; 50: 1006– 13. Keegan KA, Cookson MS. Complications of pelvic lymph node dissection for prostate cancer. Curr. Urol. Rep. 2011; 12: 203–8. Williams SK, Rabbani F. Complications of lymphadenectomy in urologic surgery. Urol. Clin. North Am. 2011; 38: 507–18, vii. Stone NN, Stock RG, Unger P. Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques. J. Urol. 1997; 158: 1891–4. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J. Urol. 2003; 169: 849–54. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006; 68: 121–5. Abdollah F, Schmitges J, Sun M et al. A critical assessment of the value of lymph node dissection at radical prostatectomy: A population-based study. The Prostate 2011; 71: 1587–94. Daneshmand S, Quek ML, Stein JP et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J. Urol. 2004; 172 (6 Pt 1): 2252–5. Boorjian SA, Thompson RH, Siddiqui S et al. Long-term outcome after radical prostatectomy for patients with lymph node positive prostate cancer in the prostate specific antigen era. J. Urol. 2007; 178 (3 Pt 1): 864–70, discussion 70-1. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N. Engl. J. Med. 1999; 341: 1781–8. 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.
940
27. Da Pozzo LF, Cozzarini C, Briganti A et al. Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur. Urol. 2009; 55: 1003–11. 28. Masterson TA, Bianco FJ Jr, Vickers AJ et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J. Urol. 2006; 175: 1320–4, discussion 4–5. 29. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur. Urol. 2007; 52: 29–37. 30. Pagliarulo V, Hawes D, Brands FH et al. Detection of occult lymph node metastases in locally advanced node-negative prostate cancer. J. Clin. Oncol. 2006; 24: 2735–42.
Picardo and Vivian
31. Bhatta-Dhar N, Reuther AM, Zippe C, Klein EA. No difference in six-year biochemical failure rates with or without pelvic lymph node dissection during radical prostatectomy in low-risk patients with localized prostate cancer. Urology 2004; 63: 528–31. 32. DiMarco DS, Zincke H, Sebo TJ, Slezak J, Bergstralh EJ, Blute ML. The extent of lymphadenectomy for pTXNO prostate cancer does not affect prostate cancer outcome in the prostate specific antigen era. J. Urol. 2005; 173: 1121–5. 33. Berglund RK, Sadetsky N, DuChane J, Carroll PR, Klein EA. Limited pelvic lymph node dissection at the time of radical prostatectomy does not affect 5-year failure rates for low, intermediate and high risk prostate cancer: results from CaPSURE. J. Urol. 2007; 177: 526–9, discussion 9–30.
© 2015 Royal Australasian College of Surgeons
Extended pelvic lymph node dissection for clinically localized prostate cancer: a West Australian experience Alarick Picardo and Justin Vivian Urology Department, St John of God Hospital, Perth, Western Australia, Australia
Key words lymph node dissection, radical prostatectomy, robotic. Correspondence Dr Alarick Picardo, Urology Department, St John of God Hospital, 12 Salvado Road, Subiaco, WA 6008, Australia. Email: [email protected] A. Picardo MBBS; J. Vivian FRACS (Urology). The early results were presented at the WA section meeting of USANZ in 2011. Accepted for publication 21 January 2015. doi: 10.1111/ans.13035
Abstract Background: The role and type of pelvic lymph node dissection for clinically localized prostate cancer is controversial in Australia. Our study aims to determine the incidence of pelvic lymph node involvement and the complication rate of extended lymphadenectomy in a group of West Australian patients who underwent a robotic assisted radical prostatectomy plus extended pelvic lymph node dissection. Method: Forty-nine patients underwent a robotic assisted radical prostatectomy with extended pelvic lymph node dissection between 2008 and 2012 by a single private urological surgeon. The inclusion criteria for the extended lymph node dissection were clinical localized, intermediate and high-risk prostate cancer based on preoperative D’Amico classification. Results: Of the 49 patients, eight patients had positive nodes giving a nodal positivity rate of 16.33%. Six patients had a complication giving a total complication rate of 12.24%. Three of these complications have been attributed to the nodal dissection, thus giving an extended pelvic lymph node dissection complication rate of 6.12%. Conclusion: Rates of nodal involvement in our West Australian cohort are in keeping with those published in the literature. Extended pelvic lymph node dissection can be performed with an acceptable complication rate. Further research is required to investigate the therapeutic role of pelvic lymph node dissection.
Introduction The role of pelvic lymph node dissection in the treatment of prostate cancer is controversial. In Australia, there are no national guidelines on whom to perform a nodal dissection. There are international organizations such as the American Urological Association, National Clinical Cancer Network and European Urological Association that have guidelines pertaining to this subject. Unfortunately, these recommendations and guidelines conflict with one another making clinical decisions more difficult. To our knowledge, in Western Australia, an extended pelvic lymph node dissection is not commonly performed with radical prostatectomy, especially for intermediate-risk disease. This contrasts to the recommendations of international urological organizations, listed in Table 1,1–3 that suggest using nomograms to stratify patients according to the risk of lymph node involvement. Importantly, these guidelines were based on nomograms aimed at predicting the presence of lymph node involvement from limited or standard nodal dissections, and subsequently, the true incidence of nodal involvement may be higher than expected. More recently, Briganti et al. have published their nomogram for predicting lymph ANZ J Surg 85 (2015) 936–940
node involvement based on patients who have an extended pelvic nodal dissection.4 Our study reports the incidence of nodal involvement and the complication rate of extended nodal dissection in a group of Western Australian patients with clinically localized, intermediate to highrisk prostate cancer.
Methods Patient population Between June 2008 and June 2012, 49 patients underwent a robotic assisted radical prostatectomy with an extended pelvic lymph node dissection by a single urologist in Western Australia. Inclusion criteria to be offered this treatment were an intermediate or high D’Amico score.5 Table 2 lists baseline patient characteristics.
Surgical technique Patients underwent a robotic assisted extended pelvic lymph node dissection similar to that described by Feicke et al.6 Of note, the © 2015 Royal Australasian College of Surgeons
ePLND for prostate cancer
937
external iliac nodes, obturator nodes and internal iliac nodes were removed; however, presacral lymph nodes described by some authors as part of an extended pelvic lymph node dissection (ePLND) were not removed.
Results A median of 17 (average 17.7, standard deviation 6.1) nodes were removed per patient. Eight patients had positive lymph nodes giving Table 1 Pelvic lymph node dissection recommendations from major urological organizations Organization
Recommendation
EAU
Extended pelvic lymph node dissection should be performed in intermediate-risk, localized PCa if the estimated risk for positive lymph nodes exceeds 5%, as well as in high-risk cases. Pelvic lymph node dissection is generally reserved for patients with higher risk of nodal involvement Extended pelvic lymph node dissection for patients with >2% predicted probability of nodal metastases
AUA NCCN
AUA, American Urological Association; EAU, European Association of Urology; NCCN, National Cancer Council Network; PCa, prostate cancer.
a nodal positivity rate of 16.3%. Table 3 shows the characteristics of all lymph node-positive patients. Five patients, all with positive lymph nodes, had biochemical failure, defined as a detectable, rising post-operative prostate-specific antigen (PSA). Four of these patients were commenced on androgen deprivation therapy and one received adjuvant radiotherapy as surgical margins were positive. The other three patients with positive lymph nodes remain under close surveillance for biochemical recurrence. The average additional operative time required for the extended nodal dissection was 45.7 min. Complications were graded according to the modified Clavien classification7 as seen in Table 4. Overall complication rate for radical robotic assisted prostatectomy with extended pelvic lymph node dissection was 12.2%.
Discussion This study shows rates of lymphatic metastases in Australian men undergoing this staging procedure are similar to those presented in the international literature. Complication rates are also similar to those reported previously. Pelvic lymph node dissection in localized prostate cancer is a controversial topic because of a lack of randomized controlled trials
Table 2 Baseline patient characteristics Number of patients Median age, year (range) Median PSA, ng/mL (range) Biopsy Gleason score, no. (%) 3+4=7 4+3=7 4+4=8 4+5=9 Clinical stage, no. (%) cT1c cT2a cT2b cT2c cT3 Percentage positive cores on biopsy, no. (%) ≤25% 25–≤50% 50–≤75% >75%
Total 49
LN+ 8
LN− 41
63 (45–74) 7.6 (3.3–56.8)
65 (55–74) 11.15 (7.3–56.8)
63 (45–73) 7.4 (3.3–13.8)
14 (28.5%) 23 (46.9%) 9 (18.4%) 3 (6.1%)
1 (12.5%) 2 (25.0%) 3 (37.5%) 2 (25.0%)
13 (31.5%) 21 (51.2%) 6 (14.6%) 1 (2.4%)
21 (42.9%) 12 (24.5%) 9 (18.4%) 6 (12.2%) 1 (2.0%)
1 (12.5%) 1 (12.5%) 3 (37.5%) 2 (25.0%) 1 (12.5%)
20 (48.9%) 11 (26.8%) 6 (14.6%) 4 (9.8%) 0 (0%)
12 (25%) 10 (20.8%) 10 (20.8%) 16 (33.3%)
1 (12.5%) 2 (25.0%) 0 (0.0%) 5 (62.5%)
11 (26.8%) 8 (19.5%) 10 (24.4%) 11 (26.8%)
PSA, prostate-specific antigen.
Table 3 Node-positive patients Patient
1 2 3 4 5 6 7 8
Biopsy Gleason score 4 4 3 4 4 4 4 4
+ + + + + + + +
3 3 4 5 5 4 4 4
= = = = = = = =
7 7 7 9 9 8 8 8
Pathologic Gleason score 4 4 3 4 5 4 4 4
+ + + + + + + +
3 3 4 5 4 3 4 3
= = = = = = = =
7 7 7 9 9 7 8 7
PSA, prostate-specific antigen.
© 2015 Royal Australasian College of Surgeons
Clinical stage
Pathological Stage
PSA
Surgical Margin
Tumour volume (mL)
Proportion nodes positive
Biochemical recurrence
cT3 cT2a cT1c cT2c cT2b cT2b cT2b cT2c
pT3a pT3a pT3a pT3b pT3b pT3b pT3b pT3a
7.3 12.3 13 9.5 10 56.8 9.9 20
Negative Negative Negative Positive Negative Positive Positive Negative
8.03 12.2 10.3 31.8 9.4 14.1 21.2 6.6
3/16 4/26 1/11 3/18 1/20 1/18 2/10 4/14
Yes No No Yes Yes Yes No Yes
938
Picardo and Vivian
Table 4 Complications following radical prostatectomy and ePLND as per Clavien Dindo classification Number of complications Grade I
2
Grade II Grade III Grade IV
0 1 3
Total
6
Types of complications (number of patients)
Percentage of total
Ileus (1) Anastomotic leak (1)
2/49 = 4.1%
Incisional hernia (1) Pulmonary embolism (1) Septicaemia secondary to infected lymphocele (2)
1/49 = 2.0% 3/49 = 6.1%
6/49 = 12.2%
to explore the risk benefit equation. Additionally, there are discrepancies in the literature regarding definitions, indications and benefits. Currently, there are three types of lymph node dissections performed in conjunction with a radical prostatectomy – limited, standard or extended. While it is generally accepted that a limited nodal dissection removes the obturator package and the standard dissection additionally involves dissection of the external iliac nodes, there is no standardization or universally accepted operative template regarding the extended lymph node dissection. In these situations, often, urologists will dissect the obturator, external iliac, hypogastric (internal iliac) and common iliac nodes; however, additional nodes in presacral, paraaortic, pararectal and paravesical regions can be involved and dissected as illustrated in lymphoscintigraphic studies of the prostate.8–10 These studies have confirmed the lymphatic drainage of the prostate to be unique and that different nodal groups can be affected independently of each other with authors reporting that up to 40% of lymph nodal involvement (LNI) can be missed with a limited node dissection alone.11,12 This variability in the extended dissection template makes it difficult to compare results with documented average nodal yields for an ePLND ranging from 11.6 to 28.6,12,13 Our study with its mean and median nodal yield of 17.7 and 17.0, respectively, is consistent with the average reported in the literature. Additionally, our nodal positivity rate of 16.3% and the nodal positivity as a percentage of tumour stage and Gleason grade is in keeping with those published in the international literature.6,14 Interestingly, our nodal positivity yield is significantly higher than that published by Sengupta et al., which is to our knowledge the only other publication on pelvic lymph node dissection for prostate cancer in Australia.15 In their retrospective analysis, 200 men underwent a radical prostatectomy plus lymph node dissection involving the obturator package and anterior half of the internal iliac package (median nodal yield of 2), with lymph node metastases reported in 10 patients (5%). We believe our higher nodal positivity rate is due to excluding patient’s with low-risk prostate cancer (according to D’Amico classification) and by reducing understaging through performing an extended nodal dissection. Complications from pelvic lymph node dissection have been reported at rates ranging from 5% to over 35%.16–19 The most common complications are lymphoceles, thromboembolic complications, neurologic injury, ureteric injury or vascular injuries. The complication rate for an ePLND is higher than that of a limited or standard dissection, with many authors showing particularly higher
rates of lymphocele formation.17 In our study, two patients developed sepsis secondary to an infected lymphocele and another developed a pulmonary embolism secondary to deep vein thrombosis. Other minor complications encountered were a post-operative ileus, an incisional hernia and an anastomotic leak, all managed conservatively. The total complication rate was 12.2%, which is well within the accepted range for a radical prostatectomy and node dissection. Furthermore, if we attribute the lymphoceles and thromboembolic complications to the lymphadenectomy, then the complication rate for the extended pelvic lymph node dissection is only 6.1%. While this is reasonably low, it is important to remember that these complications were Clavien class III or IV complications (potentially life threatening requiring intensive care management) and although all patients had good final outcomes, it is important to always consider the mortality and morbidity of this additional procedure and weigh it against its benefits. This is the critical question with pelvic lymph node dissection and in general, there are two main reasons why a pelvic node dissection is advocated. Firstly, knowing if there are lymphatic metastases provides better prognostic information. Secondly, there is a proposed therapeutic benefit.20,21 While new imaging and nuclear medicine techniques are being investigated, currently, a PLND is the only available technique that accurately determines nodal status that then provides information on prognosis. Patients with nodal metastases have a significantly poorer outcome as shown in a large population-based study where the 5-year cancer-specific mortality in nodal negative T2 patients is 3.9% compared with 20.6% in node-positive patients.22 Additionally, many authors have reported that the number of positive nodes or positive nodal density is proportional to the risk of biochemical failure.21,23,24 Knowing nodal status may influence the decision to use adjuvant androgen deprivation treatment, which has been shown to be beneficial.22 It may encourage closer monitoring for biochemical failure.25,26 In high-risk patients, or those who do not achieve biochemical cure, it may also influence the decision to use adjuvant or salvage radiotherapy.27 Several studies report a potential therapeutic benefit for an extended lymphadenectomy. They report improved cancer-specific survival and reduced biochemical recurrence in patients who undergo a pelvic lymph node dissection, even in nodal negative patients.21,28,29 It is suggested that this therapeutic effect is due to the removal of occult micrometastatic disease and there is some evidence to support this explanation. Using immunohistochemistry, Pagliarulo et al. re-reviewed 3914 nodes from 180 N0 patients and found occult tumour cells present in the nodes of 24 patients (13.3%).30 This finding indicates the incidence of true lymph node involvement is higher than reported. Despite this being an adequate explanation for those studies that show improved outcomes, other papers have failed to show any survival benefit following lymphadenectomy or therapeutic benefits of extended over limited dissections.31–33 Furthermore, Abdollah et al. has shown in his population-based study using the Surveillance, Epidemiology and End Results (SEER) registry that while patients treated with prostatectomy without nodal dissection (pNx) have a less favourable survival © 2015 Royal Australasian College of Surgeons
ePLND for prostate cancer
rate than patients who have a nodal dissection and are truly node negative (pN0), the difference is very modest (0.8% at 10 years).22 The author had performed 50 robotic assisted radical prostatectomies before starting performing extended lymph node dissections. The median additional time for performing this surgery was 46 min but in the initial experience, it was approximately 90 min. The average total theatre time for these procedures was 303 min. Increased length of procedural time has been associated with increased complication rates though this was not observed in this study. In the authors’ opinion, the rationale for performing an extended pelvic lymph node dissection in high-risk prostate cancer justifies the risk as the additional information obtained helps guide subsequent decision making. In intermediate-risk disease, where the rate of node positivity is less, treatment should be individualized by counselling patients regarding the potential risks and benefits of this additional procedure. This would be an ideal subject for a treatment study, either randomized controlled or a prospective cohort trial.
Conclusion The role of pelvic lymph node dissection in the treatment of localized prostate cancer will remain a controversial issue until further studies validate its proposed therapeutic benefit. If a dissection is to be performed, the most value will be obtained from an extended pelvic lymph node dissection, which can be performed with an acceptable complication rate. Further research is essential to investigate the therapeutic benefits of a lymph node dissection as well as adjuvant therapies for patients with nodal involvement.
References 1. NCCN Clinical Practice Guidelines in Oncology – Prostate Cancer. 2013. [Cited 20 May 2013.] Available from URL: http://www.nccn.org/ professionals/physician_gls/pdf/prostate.pdf. Ver 2. 2. American Urological Association. Guideline for the Management of Clinically Localized Prostate Cancer. 2007. [Cited 16 Jan 2012.] Available from URL: http://www.auanet.org/common/pdf/education/ clinical-guidance/Prostate-Cancer.pdf 3. European Association of Urology. Guidelines on Prostate Cancer. 2011 [Cited 16 Jan 2012.] Available from URL: http://www.uroweb.org/gls/ pdf/08_Prostate_Cancer%20September%2022nd%202011.pdf 4. 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. 5. D’Amico AV, Whittington R, Malkowicz SB et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280: 969–74. 6. Feicke A, Baumgartner M, Talimi S et al. Robotic-assisted laparoscopic extended pelvic lymph node dissection for prostate cancer: surgical technique and experience with the first 99 cases. Eur. Urol. 2009; 55: 876–83. 7. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 2004; 240: 205–13. 8. de Bonilla-Damia A, Roberto Brouwer O, Meinhardt W, Valdes-Olmos RA. Lymphatic drainage in prostate carcinoma assessed by
© 2015 Royal Australasian College of Surgeons
939
9. 10.
11.
12.
13.
14.
15.
16.
17. 18. 19.
20.
21.
22.
23.
24.
25.
26.
lymphoscintigraphy and SPECT/CT: its importance for the sentinel node procedure. Revista espanola de medicina nuclear e imagen molecular 2012; 31: 66–70. Cellini N, Luzi S, Mantini G et al. Lymphatic drainage and CTV in carcinoma of the prostate. Rays 2003; 28: 337–41. Jeschke S, Burkhard FC, Thurairaja R, Dhar N, Studer UE. Extended lymph node dissection for prostate cancer. Curr. Urol. Rep. 2008; 9: 237–42. Heesakkers RA, Jager GJ, Hovels AM et al. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging. Radiology 2009; 251: 408–14. Heidenreich A, Varga Z, Von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J. Urol. 2002; 167: 1681–6. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J. Urol. 2004; 172 (5 Pt 1): 1840–4. Wyler SF, Sulser T, Seifert HH et al. Laparoscopic extended pelvic lymph node dissection for high-risk prostate cancer. Urology 2006; 68: 883–7. Sengupta S, Weerakoon M, Sethi K, Ischia J, Webb DR. Algorithm for selecting men for pelvic lymph node dissection (PLND) during radical prostatectomy based on clinical risk factors in an Australian population. BJU Int. 2012; 109 (Suppl. 3): 48–51. Briganti A, Chun FK, Salonia A et al. Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur. Urol. 2006; 50: 1006– 13. Keegan KA, Cookson MS. Complications of pelvic lymph node dissection for prostate cancer. Curr. Urol. Rep. 2011; 12: 203–8. Williams SK, Rabbani F. Complications of lymphadenectomy in urologic surgery. Urol. Clin. North Am. 2011; 38: 507–18, vii. Stone NN, Stock RG, Unger P. Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques. J. Urol. 1997; 158: 1891–4. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J. Urol. 2003; 169: 849–54. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006; 68: 121–5. Abdollah F, Schmitges J, Sun M et al. A critical assessment of the value of lymph node dissection at radical prostatectomy: A population-based study. The Prostate 2011; 71: 1587–94. Daneshmand S, Quek ML, Stein JP et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J. Urol. 2004; 172 (6 Pt 1): 2252–5. Boorjian SA, Thompson RH, Siddiqui S et al. Long-term outcome after radical prostatectomy for patients with lymph node positive prostate cancer in the prostate specific antigen era. J. Urol. 2007; 178 (3 Pt 1): 864–70, discussion 70-1. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N. Engl. J. Med. 1999; 341: 1781–8. 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.
940
27. Da Pozzo LF, Cozzarini C, Briganti A et al. Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur. Urol. 2009; 55: 1003–11. 28. Masterson TA, Bianco FJ Jr, Vickers AJ et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J. Urol. 2006; 175: 1320–4, discussion 4–5. 29. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur. Urol. 2007; 52: 29–37. 30. Pagliarulo V, Hawes D, Brands FH et al. Detection of occult lymph node metastases in locally advanced node-negative prostate cancer. J. Clin. Oncol. 2006; 24: 2735–42.
Picardo and Vivian
31. Bhatta-Dhar N, Reuther AM, Zippe C, Klein EA. No difference in six-year biochemical failure rates with or without pelvic lymph node dissection during radical prostatectomy in low-risk patients with localized prostate cancer. Urology 2004; 63: 528–31. 32. DiMarco DS, Zincke H, Sebo TJ, Slezak J, Bergstralh EJ, Blute ML. The extent of lymphadenectomy for pTXNO prostate cancer does not affect prostate cancer outcome in the prostate specific antigen era. J. Urol. 2005; 173: 1121–5. 33. Berglund RK, Sadetsky N, DuChane J, Carroll PR, Klein EA. Limited pelvic lymph node dissection at the time of radical prostatectomy does not affect 5-year failure rates for low, intermediate and high risk prostate cancer: results from CaPSURE. J. Urol. 2007; 177: 526–9, discussion 9–30.
© 2015 Royal Australasian College of Surgeons
