Fax: (212) 717-3169
Temporal trends and predictors of pelvic lymph node dissection in open or minimally invasive radical prostatectomy†
Article first published online: 15 MAR 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 17, pages 3933–3942, 1 September 2011
How to Cite
Feifer, A. H., Elkin, E. B., Lowrance, W. T., Denton, B., Jacks, L., Yee, D. S., Coleman, J. A., Laudone, V. P., Scardino, P. T. and Eastham, J. A. (2011), Temporal trends and predictors of pelvic lymph node dissection in open or minimally invasive radical prostatectomy. Cancer, 117: 3933–3942. doi: 10.1002/cncr.25981
We gratefully acknowledge Joshua Mirkin for assistance with Medicare billing codes and reimbursement calculations and Michael Newman for editorial assistance. We also acknowledge the Applied Research Program (National Cancer Institute); the Surveillance, Epidemiology, and End Results (SEER) Program registries; the Centers for Medicare and Medicaid Services, and Information Management Services, Inc., for the SEER-Medicare linkage and guidance in the use and interpretation of these data.
- Issue published online: 19 AUG 2011
- Article first published online: 15 MAR 2011
- Manuscript Accepted: 3 JAN 2011
- Manuscript Revised: 15 DEC 2010
- Manuscript Received: 29 SEP 2010
- National Institutes of Health. Grant Number: T32-CA82088
- National Cancer Institute. Grant Numbers: P50-CA92629, CA118189-01A2
- Sidney Kimmel Center for Prostate and Urologic Cancers
- National Institutes of Health. Grant Number: 1RC1CA146516-01
- prostate cancer;
- lymph nodes;
- Surveillance, Epidemiology, and End Results-Medicare;
- minimally invasive surgery;
- open, robotic, and laparoscopic radical prostatectomy
Pelvic lymph node dissection (PLND) is an important component of prostate cancer staging and treatment, especially for surgical patients who have high-risk tumor features. It is not clear how the shift from open radical prostatectomy (ORP) to minimally invasive radical prostatectomy (MIRP) has affected the use of PLND. The objectives of this study were to identify predictors of PLND and to assess the impact of surgical technique in a contemporary, population-based cohort.
In Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified men who underwent ORP or MIRP for prostate cancer during 2003 to 2007. The impact of surgical approach on PLND was evaluated, and interactions were examined between surgical procedure, prostate-specific antigen (PSA), and Gleason score with the analysis controlled for patient and tumor characteristics.
Of 6608 men who underwent ORP or MIRP, 70% (n = 4600) underwent PLND. The use of PLND declined over time both overall and within subgroups defined by procedure type. PLND was 5 times more likely in men who underwent ORP than in men who underwent MIRP when the analysis was controlled for patient and tumor characteristics. Elevated PSA and biopsy Gleason score, but not clinical stage, were associated with a greater odds of PLND in both the ORP group and the MIRP group. However, the magnitude of the association between these factors and PLND was significantly greater for patients in the ORP group.
PLND was less common among men who underwent MIRP, independent of tumor risk factors. A decline in PLND rates was not fully explained by an increase in MIRP. The authors concluded that these trends may signal a surgical approach-dependent disparity in prostate cancer staging and therapy. Cancer 2011;. © 2011 American Cancer Society.
The incidence of prostate cancer in the general population is estimated at 192,280 new diagnoses and 27,360 mortalities in 2009.1 The improvements in prognosis related to innovations in diagnosis and treatment are clearly identifiable.2 The surgical management of prostate cancer is a mainstay of therapy for men with localized disease, even for those who have high-risk, clinically localized cancers.3 The standard of surgical care, open radical prostatectomy (ORP), has been overshadowed in the United States by robotic-assisted laparoscopic techniques.4, 5 This shift is related to the purported improved postoperative recovery, diminished blood loss, and improved quality-of-life outcomes with minimally invasive radical prostatectomy (MIRP), although the market appeal of robotic surgery also has played a central role.6, 7 Current literature emphasizes surgical experience8 and case volume9, 10 as primary contributors to surgical outcomes rather than surgical modality. In addition, although the findings still are debated, recent population-based analyses suggest that MIRP and ORP have similar oncologic and functional outcomes.11, 12
Pelvic lymph node dissection (PLND) is a well accepted staging modality in prostate cancer, although its clinical indication in lower risk patients and its therapeutic benefits are controversial.13 Despite this, similar patients undergoing either MIRP or ORP theoretically should be subjected to identical preoperative risk-based decision-making regarding PLND. Various prediction tools are used for this purpose14 and serve as the basis for National Comprehensive Cancer Network15 and American Urological Association16 guidelines. Although investigations have evaluated how the uptake of MIRP is associated with surgical efficacy, potential disparities in PLND use according to the patient's preoperative risk currently remain unknown.17, 18 The objective of our current study was to describe temporal trends and identify predictors of pelvic lymphadenectomy in a population-based cohort of older men with prostate cancer.
MATERIALS AND METHODS
The study cohort was identified from Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims. SEER, which is sponsored by the National Cancer Institute, is a consortium of population-based cancer registries in selected geographic areas that cover approximately 25% of the US population.19 For all patients who are diagnosed with cancer in their geographic areas, the SEER registries collect data regarding site and extent of disease, surgery and radiation therapy planned or administered in the first course of cancer-directed therapy, and sociodemographic characteristics, and active follow-up is conducted to collect the date and cause of death.20 For patients with cancer aged ≥65 years who reside in SEER areas, Medicare claims have been linked to SEER files. Medicare is the primary health insurer for 97% of Americans aged ≥65 years and covers inpatient and outpatient hospital care (Parts A and B, respectively). Compared with the elderly US population, the SEER-Medicare population has similar age and sex distributions but has a smaller proportion of nonwhites, and individuals in SEER-Medicare are more likely to live in urban areas and affluent areas.20, 21
Patients who underwent radical prostatectomy (RP) and PLND from 2003 to 2007 were identified by International Classification of Disease-Ninth Revision code RP-60.5 and by Current Procedural Terminology codes ORP-55866, MIRP-55840, 55842, and 55845. Our analysis included all prostate cancers that were designated as T1 through T3 according to the SEER modification of the American Joint Committee on Cancer staging system. Men who had T4 disease or who presented with metastasis were excluded from the analysis. Other exclusion criteria were a diagnosis of prostate cancer only at the time of death, a history of previous malignancy, and/or radiotherapy before prostate cancer surgery. We also excluded men who were not enrolled in both Part A and Part B of Medicare and those who were enrolled in a managed care organization at the time of diagnosis or during the year before diagnosis because of the absence of Medicare claims. The sample was limited to men aged ≥66 years, so that a full year of claims before diagnosis was available for estimating comorbidity. We also excluded men who were missing information about preoperative prostate-specific antigen (PSA) level, Gleason score, or clinical tumor stage.
The outcome of interest was receipt of a bilateral PLND, as identified in SEER. By using the SEER variable for the scope of regional lymph node surgery, we defined the outcome as removal of at least 4 regional lymph nodes. Patients who underwent only a lymph node aspiration or biopsy and those for whom the scope of regional lymph node surgery was unknown were categorized as not having undergone lymph node dissection.
We examined several characteristics that have been hypothesized to predict receipt of PLND. The demographic characteristics that we used included age, race, median income in the census tract of residence, urban- rural residence, and geographic location. Marital status was included as a measure of social support. Metropolitan versus nonmetropolitan county was included to adjust for potential confounding by systematic practice variation among academic and community institutions. Tumor characteristics included clinical tumor stage, preoperative PSA level, biopsy Gleason score, and surgical procedure (ORP vs MIRP). Because SEER did not record exact PSA values until 2004, we used preoperative PSA levels categorized as elevated, borderline, normal, or unknown. In separate analyses, we used numeric PSA values for patients who were diagnosed during or after 2004. Comorbidity was estimated using the Charlson comorbidity score and was based on inpatient claims in the 365 days before prostate cancer diagnosis.
We used multivariate logistic regression to estimate the adjusted effects of each variable on the likelihood of undergoing PLND. We also performed analyses stratified by surgical procedure (ORP vs MIRP) to assess whether this modified the impact of important predictors, such as tumor stage, Gleason score, and PSA level, on the receipt of PLND. In these analyses, Gleason score was dichotomized at a threshold of 7 (Gleason score 2-6 vs ≥7), and PSA was dichotomized at 10 ng/mL (PSA ≤10 ng/mL vs >10 ng/mL). These categories correspond with validated prognostic models, which identify Gleason score and PSA values associated with a probability ≥2% of lymph node metastasis—a well established criterion for PLND.14, 22, 23 These classifications also effectively distinguish between patients at low risk for biochemical recurrence after definitive local therapy from intermediate-risk and high-risk patients.24 Adjusted odds ratios (ORs, 95% confidence intervals (CIs), and 2-sided P values were estimated in all multivariate regression analyses. A Cochrane-Armitage test was used to assess trends in PLND over time, and an interaction between surgical procedure (ORP vs MIRP) and year was included in a separate multivariate logistic regression model to test differences in trends by surgical procedure.
We identified 6608 men who were diagnosed with clinical T1 through T3 prostate cancer between 2003 and 2005 and underwent radical prostatectomy (RP) between 2003 and 2007. Of these, 4534 men (69%) underwent ORP, 1190 men (18%) underwent MIRP, and 884 men (13%) underwent RP with a surgical approach that was not specified. Overall, 4600 men (70%) underwent PLND. In unadjusted analyses, there were no significant associations between the receipt of PLND and race, age, or other demographic characteristics (Table 1). Patients who underwent ORP represented 80% of the men who underwent PLND but only 45% of those who did undergo PLND (P < .0001). The receipt of PLND increased with increasing preoperative PSA level and Gleason score. However, a substantial fraction of men who had high-risk tumor features did not undergo PLND, and this relation varied by surgical approach (Table 2). For example, among the men who were diagnosed during 2004 and 2005 who had a preoperative PSA level ≥10 ng/mL, 80% underwent PLND, but PLND was omitted in 40% of the men who underwent MIRP and in only 15% of the men who underwent ORP. We observed similar patterns for other tumor features. Among the men who had stage T3 disease, 80% in the ORP group underwent PLND compared with 56% in the MIRP group. Among the men who had a Gleason score >7, higher rates of PLND for were observed in the ORP group compared with the MIRP group.
|All Patients, n=6608||PLND, n=4600||No PLND, n=2308|
|Age at diagnosis, y|
|Numeric PSA, ng/mLd|
|All Patients, n=4374||MIRP, n=1085||ORP, n=3289|
|Characteristic||No.||% PLND||No.||% PLND||No.||% PLND|
|Numeric PSA, ng/mLa|
Predictors of PLND
Controlling for patient and tumor characteristics, the odds of PLND were more than 5 times greater with ORP than with MIRP (Table 3). By using the SEER categorical PSA variable, men who had an “elevated” preoperative PSA value were not significantly more likely to undergo PLND. However, in an analysis that was limited to men who were diagnosed in 2004 and 2005, a numeric PSA value >10 ng/mL was associated with increased odds of undergoing PLND (adjusted OR, 1.77; 95% CI, 1.46-2.15). Among all men, a biopsy Gleason score ≥7 was also associated with increased odds of undergoing PLND (adjusted OR, 2.41; 95% CI, 1.88-3.10). Advanced tumor stage was not associated with PLND when the analysis was controlling for other patient and tumor characteristics. The use of PLND was not influenced by sociodemographic characteristics or comorbidity.
|Characteristic||AOR (95% CI)||P|
|RP, NOS||1.26 (1.05-1.52)|
|Age at diagnosis, y|
|Second quartile||0.96 (0.81-1.43)||NSa|
|Third quartile||1.07 (0.89-1.28)|
|Fourth quartile||1.08 (0.90-1.30)|
|Numeric PSA, ng/mLb|
|Year of surgery||0.67 (0.58-0.73)||<.0001|
Analyses stratified by surgical procedure (ORP vs MIRP) suggested that surgical approach modified the effects of Gleason score, but not PSA, on the likelihood of undergoing PLND (Table 4). The impact of PSA on PLND was similar in both surgical groups. In analyses that were limited to men who were diagnosed in 2004 and 2005, the impact of a preoperative PSA level >10 ng/mL doubled the odds of undergoing PLND among men who underwent MIRP (95% CI, 1.42-3.08) and increased the odds by approximately 1.7 (95% CI, 1.33-2.08) among men who underwent ORP. In a separate multivariate regression model (not shown), the coefficient on an interaction term for type of surgery (MIRP vs ORP) by numeric PSA value (≤10 ng/mL vs >10 ng/mL) was not statistically significant. The impact of Gleason score did vary by surgical approach. In men who underwent MIRP, a Gleason score ≥7 more than doubled the odds of undergoing PLND (95% CI, 1.87-3.10); whereas, among men who underwent ORP, the OR for those with a Gleason score ≥7 was approximately 1.8 (95% CI, 1.54-2.10). In a separate model (not shown), the coefficient on an interaction term for type of surgery by Gleason score was positive and statistically significant (P < .001), suggesting that, although a Gleason score >7 increased the odds of PLND in both groups, the magnitude of this effect was greater for men who underwent MIRP.
|MIRP, n=1190||ORP, n=4951|
|Characteristic||AOR (95% CI)||P||AOR (95% CI)||P|
|Age at Dx, y|
|70-74||0.90 (0.69-1.17)||NSa||1.04 (0.88-1.22)||NSa|
|75-79||1.32 (0.81-2.14)||1.48 (1.03-2.12)|
|≥80||1.38 (0.28-6.77)||0.79 (0.33-1.89)|
|Black||0.76 (0.41-1.38)||NSa||0.88 (0.70-1.17)||NSa|
|Other||0.86 (0.58-1.27)||1.10 (0.83-1.45)|
|Second quartile||1.29 (0.83-2.00)||NSa||0.95 (0.77-1.17)||NSa|
|Third quartile||1.48 (0.92-2.24)||1.04 (0.83-1.30)|
|Fourth quartile||1.38 (0.90-2.13)||1.06 (0.83-1.35)|
|Nonmetropolitan||1.15 (0.67-1.85)||NSa||0.80 (0.63-1.00)||<.01|
|South||0.84 (0.46-1.54)||<.05||1.07 (0.79-1.45)||NSa|
|Midwest||1.28 (0.75-2.16)||1.27 (0.93-1.93)|
|West||1.58 (1.07-2.32)||1.43 (1.13-1.84)|
|No||1.03 (0.71-1.47)||<.0001||0.92 (0.75-1.14)||<.0001|
|Unknown||0.27 (0.14-0.52)||0.26 (0.19-0.36)|
|T2||0.97 (0.75-1.23)||NSa||1.12 (0.96-1.31)||NSa|
|T3||1.62 (0.59-4.42)||1.23 (0.67-1.50)|
|Borderline||0.32 (0.16-0.64)||<.01||1.00 (0.82-1.22)||NSa|
|Elevated||0.90 (0.59-1.37)||0.98 (0.73-1.30)|
|Numeric PSA, ng/mLb|
|>10||2.09 (1.42-3.08)||<.001||1.67 (1.33-2.08)||<.0001|
|≥7||2.41 (1.87-3.10)||<.0001||1.80 (1.54-2.10)||<.0001|
|1||0.87 (0.63-1.25)||NSa||1.00 (0.82-1.22)||NSa|
|≥2||0.54 (0.27-1.10)||0.97 (0.69-1.34)|
|Year of treatment||0.67 (0.58-0.78)||<.0001||0.88 (0.82-0.95)||<.01|
There was a statistically significant decline in the use of PLND from 2003 to 2007 (P < .001; test for trend) (Fig. 1). This trend was not solely attributable to the increased use of MIRP over the period of analysis. Adjusting for surgical procedure (MIRP vs ORP), year of surgery remained a significant predictor of undergoing PLND (Table 2), and the decline was observed in both surgery subgroups (Table 3). In a separate analysis of all patients, we observed a statistically significant (P < .05), negative coefficient on an interaction between MIRP and year of surgery, suggesting that the decline in PLND over time was steeper in the MIRP group compared with the ORP group when the analysis was controlled for other patient and tumor characteristics.
In this population-based analysis of patients who underwent RP, the receipt of PLND was more common among men who had higher risk tumor features, consistent with current practice guidelines.15 However, we also observed an independent effect of surgical procedure type. The odds of undergoing PLND were more than 5 times greater for men who underwent ORP compared with their peers who underwent MIRP when the analysis was controlled for PSA level, Gleason score, age, comorbidity, and other demographic and clinical factors. Moreover, surgical approach modified the effect of Gleason score on the likelihood of undergoing PLND. Although a higher Gleason score increased the odds of undergoing PLND for all patients, the magnitude of this effect was greater in the MIRP group than in the ORP group.
There are several possible explanations for the differential receipt of PLND by surgical approach. Surgeons who are recent adopters of MIRP and, thus, are practicing on the steep, early segment of the surgical learning curve may omit PLND to reduce operative times.25, 26 Alternatively, surgeons who perform MIRP may be more concerned about technical aspects of the procedure associated with functional outcomes, such as continence and erectile function, than any possible oncologic benefit associated with PLND. Mastery of the prostatectomy segment has dominated the learning curve for MIRP, and PLND has not figured centrally in the early dissemination of this procedure.27, 28
Despite the comparable safety profile and overall feasibility of MIRP compared with ORP,29 disparities in lymph node counts have been reported.17 However, when properly performed, minimally invasive PLND can achieve a lymph node yield similar to that achieved with open PLND without increasing the risk of complications.27 Recent prospective series have further supported the technical feasibility of robotic PLND,30 especially with extended dissection templates.31, 32 Thus, MIRP should not be a prohibitive factor in accomplishing a complete oncologic resection, including PLND.33, 34
On the basis of early experience in which a concomitant PLND with RP was performed routinely for staging purposes,35 current treatment guidelines are now stage-specific, and PLND is recommended routinely for high-risk cancers and selectively for patients with lower risk disease.15, 16 This prompted the development of statistical models to predict the likelihood of lymph node metastasis based on preoperative PSA level, Gleason score, and clinical stage.14, 22 Validation of these models suggests that their predictive accuracy does not vary by surgical approach.36-38 Thus, in a man whose tumor features suggest a high risk of lymph node metastasis, it would be inappropriate to arbitrarily omit PLND because a minimally invasive technique is being used.
A properly performed PLND improves postoperative risk assessment and may provide a therapeutic benefit in selected patients with microscopic lymph node disease.39, 40 Although most men with lymph node metastasis will experience biochemical recurrence, some men achieve a sustained nondetectable PSA level.41-43 However, the prognosis for men with lymph node-positive prostate cancer still is good, with cancer-specific survival exceeding 80% at 10 years.44 Although the benefit of PLND in low-risk patients probably is modest,45 patients with elevated Gleason score, PSA level, or clinical stage have considerable predicted rates of lymph node metastasis.13 Although comorbidity has been associated with a decrease in the odds of undergoing PLND,18 we did not observe this relation when we controlled the analysis for other patient and tumor characteristics. Moreover, we observed that 26% of men with clinical stage T3 disease, 19% of men with a serum PSA level >10 ng/mL, and 24% of men with a Gleason score >7 did not undergo PLND. Contemporary criteria for identifying men at high risk of lymph node metastasis suggest that most if not all of these men with high-risk features should have undergone PLND.23
The period of our study was characterized by rapid uptake of MIRP. However, the decline in PLND over time cannot be explained by the increased use of MIRP, because we observed a decline in PLND in both the MIRP and ORP subgroups. In fact, the decline was steeper among those who underwent MIRP. If patients who underwent early MIRP were selected for more favorable characteristics, representing men with lower risk disease on average, then we would have expected an increase in PLND among patients who underwent MIRP over time, contrary to the trend we observed. Similarities in baseline tumor risk factors in both cohorts did not support preferential MIRP for lower risk patients, similar to other series.18 Thus, the accelerated decline in PLND in the MIRP cohort likely was fueled by other factors, such swifter avoidance of PLND for patients who had marginal or unproven benefit in the minimally invasive setting. Although it was not the focus of the current investigation, it may be more common in low-volume community practices than in high-volume academic medical centers,10, 18 both of which are included in the population-based SEER-Medicare dataset.17
It is also unlikely that our results are explained by financial incentives for providers. In fact, Medicare reimbursement favors greater use of PLND with MIRP, where it can be billed separately, than with ORP, where it is included in a bundled payment. In 2010, Medicare reimbursement for MIRP with PLND was approximately $1000, or 50% greater than ORP with PLND.17 The higher rate of PLND with ORP that we observed suggests that this difference in reimbursement is not promoting the overuse of PLND in patients who undergo MIRP.
Features of the SEER-Medicare population and dataset may explain some of our findings and may limit the generalizability of our conclusions. Currently, although it is estimated that the robotic platform is the most common approach for RP in the United States,46 MIRP represented only 18% of the procedures in our dataset. Although the states and metropolitan areas in the SEER Program were not likely MIRP-underserved areas during the study period, the uptake of MIRP may vary considerably across surgeons, even among those who have access to minimally invasive surgical equipment. The relatively low rate of MIRP we observed also may be explained by under use of MIRP or prostatectomy in general among men aged >66 years.47 In addition, although we were able to assess the impact of several important patient, tumor, and treatment characteristics on the likelihood of undergoing PLND, there may be other, unobserved factors that explain the differential use of this procedure, such as physician experience; hospital characteristics, such as community versus academic designation; or patient comorbidities that are not captured in the Charlson index. In addition, given the limited information regarding tumor characteristics in the SEER data, our estimates of the preoperative risk of lymph node disease were based only on preoperative PSA levels and Gleason scores. Finally, although we were able to determine whether a patient underwent bilateral PLND, definitions of standard, limited, and extended templates are not standardized across providers and were not identifiable in either SEER or Medicare data. Also, although SEER includes information regarding the number of lymph nodes removed, the anatomic location of these lymph nodes is not specified.
In conclusion, controlling for patient and tumor characteristics, the odds of PLND in men who underwent ORP was more than 5 times that of men who underwent MIRP. This association was evident even in higher risk patients, in whom the odds of PLND varied significantly with surgical approach. Oncologic principles in prostatectomy should transcend surgical technique, thereby requiring urologists to provide the same operation regardless of surgical modality. A renewed emphasis of PLND in MIRP is warranted in an effort to standardize practice patterns across techniques.
CONFLICT OF INTEREST DISCLOSURES
This work was supported in part by funds from the National Institutes of Health (grant T32-CA82088 to P.T.S. and W.T.L.), the National Cancer Institute (grant P50-CA92629 [Specialized Programs of Research Excellence] to P.T.S. and grant CA118189-01A2 to E.B.E.), the Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch (provided through the Prostate Cancer Foundation); and a Challenge grant funded by the National Institutes of Health (grant 1RC1CA146516-01 to J.A.E.).
- 1National Cancer Institute, National Institutes of Health. Prostate cancer home page. http://www.cancer.gov/cancertopics/types/prostate. Accessed November 1, 2010.
- 15Update: NCCN prostate cancer clinical practice guidelines. J Natl Compr Canc Netw. 2005; 3( suppl 1): S29-S33..
- 46Intuitive Surgical, Inc. Da Vinci Surgical System. Sunnyvale, CA: Intuitive Surgical, Inc. http://www.intuitivesurgical. com. Accessed November 1, 2010.