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Should Pelvic Lymph Node Dissection be Performed With Radical Prostatectomy?
Opposing Views
Should Pelvic Lymph Node Dissection be Performed With Radical Prostatectomy? NO “It is a wise man who said that there is no greater inequality than the equal treatment of unequals”—Felix Frankfurter INCREASINGLY, physicians are being asked to justify the rationale for treatment recommendations in the context of available scientific evidence. In the field of urological oncology it is hard to find a more controversial disease than prostate cancer, especially when it comes to screening and treatment recommendations for localized disease. A small but important nuance of treatment for localized disease worthy of discussion is that of pelvic lymph node dissection (PLND) performed at the time of radical prostatectomy (RP). From an oncological perspective, a lymph node (LN) dissection as routine could be justified if it were a significant improvement in either diagnostic staging or therapeutic cancer control, provided the cost and morbidity were acceptable. For decades it has been considered standard to perform a PLND at the time of RP. The justification for this was derived largely from a diagnostic viewpoint that pathological analysis of the LNs served as an important staging tool. In selected patients, and in particular those at high risk, the therapeutic benefit has also been debated. However, the field has advanced with the development of predictive tools and nomograms.1 These tools are now used to guide our counseling and treatment recommendations. Based on histological confirmation of LNs from men subjected to surgery, refinements in our understanding of cancer risk and the concept of risk stratification have evolved. Thus while we were increasing our clinical acumen, we were simultaneously improving our cancer detection. The net result was stage migration with a significant proportion of men with localized, good risk features at an extremely low risk to harbor LN involvement who had subsequently undergone treatment.2 There are several questions to address before endorsing PLND as a routine in all patients. Is it a 0022-5347/10/1834-1284/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1284
www.jurology.com
AND
RESEARCH, INC.
necessary component of staging and is the diagnostic information of benefit for the “average” patient? I think the answer is categorically “no” for several reasons. Most patients currently undergoing treatment in the United States are considered to be at low risk for LN involvement by risk stratification standards.1 In fact, most patients currently undergoing RP have a 3% or less risk of having positive LNs based on available nomograms. For the low risk patient, defined by prostate specific antigen (PSA) less than 10 ng/ml, clinical stage T1c and biopsy Gleason sum less than 6, the chance of LN involvement is less than 1%.3 Therefore, it is hard to justify the routine performance of a PLND in these patients. However, critics of these nomograms point out that predictive accuracy may be limited by a variety of factors, including the extent of the PLND, but nomograms based on additional clinical information, including biopsy information and tumor volume, coupled with inclusion of patients treated with extended PLND could further improve accuracy. If we acknowledge the exceedingly low diagnostic yield and minimal to no improvement in staging from routine performance of PLND in low risk patients, the next question would be is there a therapeutic benefit for the routine patient. Again, the answer for the average low risk patient would be an emphatic “no.” If we look to the scientific evidence, there is a paucity of data to guide decision making. However, of the available data the literature fails to justify the performance of a routine PLND based on cancer control. In fact, in a large series of low risk patients treated with RP there was no difference in 10-year biochemical-free survival rates for those who underwent PLND compared to those who did not (86% vs 88%, respectively).4 Additionally, others have demonstrated similar results among low risk patients with no difference in recurrence rates when treated with RP with or without PLND. To my knowledge there are no studies currently published demonstrating superiority of cancer control or survival benefit for low risk patients treated Vol. 183, 1284-1287, April 2010 Printed in U.S.A. DOI:10.1016/j.juro.2010.01.053
OPPOSING VIEWS
with RP based on the addition of PLND. This is not to say that for patients with intermediate to high risk features there could not be a therapeutic benefit, with possible improved cancer control for those in whom LN involvement is removed at the time of surgery. However, many of these patients will require an extended PLND rather than a standard dissection. Conversely, an extended PLND from a diagnostic as well as a therapeutic standpoint for a low risk patient appears to be unnecessary. Another factor to consider is the potential increased morbidity of the PLND. While generally safe, a recent review suggests the complication rate ranges varies from 2% to 51%, with a higher rate of complications with more extended dissections.5 Furthermore, this appears to be true for open and laparoscopic approaches. Fortunately, intraoperative complications are relatively few in experienced hands but vascular and obturator nerve injuries are additional risks associated with the procedure. The most common complication is the well-known lymphocele. While most lymphoceles are managed with percutaneous drain placement, some may require a secondary surgical procedure. Finally, there is an increased economic cost associated with laparoscopic pelvic lymph node dissection and, given the increasing use of robotic assisted laparo-
1285
scopic prostatectomy in the United States is approaching 70%, this additional point is significant. Recommendations for PLND were recently summarized.5 Currently, the American Urological Association recommends a PLND be “generally reserved for patients with higher risk of nodal involvement.” The European Association of Urology recommends PLND for men with intermediate or high risk prostate cancer. The National Comprehensive Cancer Network states that the PLND can be excluded for patients with a less than 7% predicted probability of lymph node metastases by nomograms. While not specifically stated in these guidelines, there appears to be general agreement that for the most common patient currently undergoing treatment for localized prostate cancer today, which is the low risk (as defined previously) patient, a PLND should not be performed routinely. For the intermediate and high risk patient, more prospective trials are needed to further define the extent of the node dissection, cost, morbidity and the true impact on cancer specific survival. Michael S. Cookson Department of Urology Vanderbilt University Nashville, Tennessee
REFERENCES 1. Stephenson AJ and Kattan MW: Nomograms for prostate cancer. BJU Int 2006; 98: 39. 2. Welch HG and Albertsen PC: Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986 –2005. J Natl Cancer Inst 2009; 101: 1325.
3. Makarov DV, Trock BJ, Humphreys EB et al: Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology 2007; 69: 1095. 4. Weight CJ, Reuther AM, Gunn PW et al: Limited pelvic lymph node dissection does not improve
YES WHEN performing radical prostatectomy for prostate cancer extended pelvic lymph node dissection should be considered for 6 reasons. 1) Histopathological examination of removed pelvic lymph nodes is the most accurate staging procedure. Imaging studies can detect only gross nodal disease with enlarged lymph nodes. Such patients can rarely be cured by surgery alone. Newer technologies, such as diffusion-weighted magnetic resonance imaging enhanced with ultrasmall superparamagnetic particles of iron oxide, which seem to allow detection of metastasis greater than 2 mm in normal sized nodes are still under investigation.1
biochemical relapse-free survival at 10 years after radical prostatectomy in patients with low-risk prostate cancer. Urology 2008; 71: 141. 5. Briganti A, Blute ML, Eastham JH et al: Pelvic lymph node dissection in prostate cancer. Eur Urol 2009; 55: 1251.
2) The sentinel node technique (detection of technetium containing lymph nodes after injection of technetium isotopes into the prostate) is of limited value because the prostate has many primary lymphatic landing sites in the pelvis.2 Only nodes in direct contact with the gamma probe can be detected but not nodes that are not specifically sought (opposite side of large pelvic vessels, presacral area, aortic bifurcation etc). Approximately 30% of metastatic nodes are not detected (false negative)3 because metastatic tissue prevents the uptake of technetium. 3) Nomograms are seldom useful because they are usually based on limited lymph node dissections not accurately representing the true prevalence of posi-
Should Pelvic Lymph Node Dissection be Performed With Radical Prostatectomy? NO “It is a wise man who said that there is no greater inequality than the equal treatment of unequals”—Felix Frankfurter INCREASINGLY, physicians are being asked to justify the rationale for treatment recommendations in the context of available scientific evidence. In the field of urological oncology it is hard to find a more controversial disease than prostate cancer, especially when it comes to screening and treatment recommendations for localized disease. A small but important nuance of treatment for localized disease worthy of discussion is that of pelvic lymph node dissection (PLND) performed at the time of radical prostatectomy (RP). From an oncological perspective, a lymph node (LN) dissection as routine could be justified if it were a significant improvement in either diagnostic staging or therapeutic cancer control, provided the cost and morbidity were acceptable. For decades it has been considered standard to perform a PLND at the time of RP. The justification for this was derived largely from a diagnostic viewpoint that pathological analysis of the LNs served as an important staging tool. In selected patients, and in particular those at high risk, the therapeutic benefit has also been debated. However, the field has advanced with the development of predictive tools and nomograms.1 These tools are now used to guide our counseling and treatment recommendations. Based on histological confirmation of LNs from men subjected to surgery, refinements in our understanding of cancer risk and the concept of risk stratification have evolved. Thus while we were increasing our clinical acumen, we were simultaneously improving our cancer detection. The net result was stage migration with a significant proportion of men with localized, good risk features at an extremely low risk to harbor LN involvement who had subsequently undergone treatment.2 There are several questions to address before endorsing PLND as a routine in all patients. Is it a 0022-5347/10/1834-1284/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1284
www.jurology.com
AND
RESEARCH, INC.
necessary component of staging and is the diagnostic information of benefit for the “average” patient? I think the answer is categorically “no” for several reasons. Most patients currently undergoing treatment in the United States are considered to be at low risk for LN involvement by risk stratification standards.1 In fact, most patients currently undergoing RP have a 3% or less risk of having positive LNs based on available nomograms. For the low risk patient, defined by prostate specific antigen (PSA) less than 10 ng/ml, clinical stage T1c and biopsy Gleason sum less than 6, the chance of LN involvement is less than 1%.3 Therefore, it is hard to justify the routine performance of a PLND in these patients. However, critics of these nomograms point out that predictive accuracy may be limited by a variety of factors, including the extent of the PLND, but nomograms based on additional clinical information, including biopsy information and tumor volume, coupled with inclusion of patients treated with extended PLND could further improve accuracy. If we acknowledge the exceedingly low diagnostic yield and minimal to no improvement in staging from routine performance of PLND in low risk patients, the next question would be is there a therapeutic benefit for the routine patient. Again, the answer for the average low risk patient would be an emphatic “no.” If we look to the scientific evidence, there is a paucity of data to guide decision making. However, of the available data the literature fails to justify the performance of a routine PLND based on cancer control. In fact, in a large series of low risk patients treated with RP there was no difference in 10-year biochemical-free survival rates for those who underwent PLND compared to those who did not (86% vs 88%, respectively).4 Additionally, others have demonstrated similar results among low risk patients with no difference in recurrence rates when treated with RP with or without PLND. To my knowledge there are no studies currently published demonstrating superiority of cancer control or survival benefit for low risk patients treated Vol. 183, 1284-1287, April 2010 Printed in U.S.A. DOI:10.1016/j.juro.2010.01.053
OPPOSING VIEWS
with RP based on the addition of PLND. This is not to say that for patients with intermediate to high risk features there could not be a therapeutic benefit, with possible improved cancer control for those in whom LN involvement is removed at the time of surgery. However, many of these patients will require an extended PLND rather than a standard dissection. Conversely, an extended PLND from a diagnostic as well as a therapeutic standpoint for a low risk patient appears to be unnecessary. Another factor to consider is the potential increased morbidity of the PLND. While generally safe, a recent review suggests the complication rate ranges varies from 2% to 51%, with a higher rate of complications with more extended dissections.5 Furthermore, this appears to be true for open and laparoscopic approaches. Fortunately, intraoperative complications are relatively few in experienced hands but vascular and obturator nerve injuries are additional risks associated with the procedure. The most common complication is the well-known lymphocele. While most lymphoceles are managed with percutaneous drain placement, some may require a secondary surgical procedure. Finally, there is an increased economic cost associated with laparoscopic pelvic lymph node dissection and, given the increasing use of robotic assisted laparo-
1285
scopic prostatectomy in the United States is approaching 70%, this additional point is significant. Recommendations for PLND were recently summarized.5 Currently, the American Urological Association recommends a PLND be “generally reserved for patients with higher risk of nodal involvement.” The European Association of Urology recommends PLND for men with intermediate or high risk prostate cancer. The National Comprehensive Cancer Network states that the PLND can be excluded for patients with a less than 7% predicted probability of lymph node metastases by nomograms. While not specifically stated in these guidelines, there appears to be general agreement that for the most common patient currently undergoing treatment for localized prostate cancer today, which is the low risk (as defined previously) patient, a PLND should not be performed routinely. For the intermediate and high risk patient, more prospective trials are needed to further define the extent of the node dissection, cost, morbidity and the true impact on cancer specific survival. Michael S. Cookson Department of Urology Vanderbilt University Nashville, Tennessee
REFERENCES 1. Stephenson AJ and Kattan MW: Nomograms for prostate cancer. BJU Int 2006; 98: 39. 2. Welch HG and Albertsen PC: Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986 –2005. J Natl Cancer Inst 2009; 101: 1325.
3. Makarov DV, Trock BJ, Humphreys EB et al: Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology 2007; 69: 1095. 4. Weight CJ, Reuther AM, Gunn PW et al: Limited pelvic lymph node dissection does not improve
YES WHEN performing radical prostatectomy for prostate cancer extended pelvic lymph node dissection should be considered for 6 reasons. 1) Histopathological examination of removed pelvic lymph nodes is the most accurate staging procedure. Imaging studies can detect only gross nodal disease with enlarged lymph nodes. Such patients can rarely be cured by surgery alone. Newer technologies, such as diffusion-weighted magnetic resonance imaging enhanced with ultrasmall superparamagnetic particles of iron oxide, which seem to allow detection of metastasis greater than 2 mm in normal sized nodes are still under investigation.1
biochemical relapse-free survival at 10 years after radical prostatectomy in patients with low-risk prostate cancer. Urology 2008; 71: 141. 5. Briganti A, Blute ML, Eastham JH et al: Pelvic lymph node dissection in prostate cancer. Eur Urol 2009; 55: 1251.
2) The sentinel node technique (detection of technetium containing lymph nodes after injection of technetium isotopes into the prostate) is of limited value because the prostate has many primary lymphatic landing sites in the pelvis.2 Only nodes in direct contact with the gamma probe can be detected but not nodes that are not specifically sought (opposite side of large pelvic vessels, presacral area, aortic bifurcation etc). Approximately 30% of metastatic nodes are not detected (false negative)3 because metastatic tissue prevents the uptake of technetium. 3) Nomograms are seldom useful because they are usually based on limited lymph node dissections not accurately representing the true prevalence of posi-