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. Author manuscript; available in PMC: 2020 Oct 15.
Published in final edited form as: J Urol. 2017 Dec 15;199(5):1238–1244. doi: 10.1016/j.juro.2017.11.121

Differences in Survival by Receipt of Lymph Node Dissection in Patients with Invasive Penile cancer: Results from the National Cancer Database.

Andres F Correa 1, Elizabeth Handorf 2, Shreyas S Joshi 3, Daniel M Geynisman 4, Alexander Kutikov 5, David Y Chen 5, Robert G Uzzo 5, Rosalia Viterbo 5, Richard E Greenberg 5, Marc C Smaldone 5
PMCID: PMC7557119  NIHMSID: NIHMS1631741  PMID: 29248557

Abstract

Background:

Inguinal lymphadenectomy (I-LND) remains underutilized in patients with invasive penile cancer. Using a large national cancer registry, we assessed temporal trends in I-LND utilization and evaluated the impact of I-LND on the survival in patients in whom I-LND is an absolute indication per NCCN guidelines (T1b-4 N0/x-1).

Methods:

The National Cancer Database (NCDB) was queried for all non-metastatic penile patients with T1b-4 N0/X-N1 squamous cell carcinoma of the penis from 2004–2014. Adjusting for patient, demographic, and clinicopathologic characteristics, multivariable logistic regression models were used to examine the association between available covariates and receipt of I-LND. Cox-proportional hazards regression analyses were then used to assess the impact of clinical and pathological variables on overall survival. A propensity score weighted analysis was performed to assess the effect of I-LND in overall survival.

Results:

A total of 2224 patients met criteria for analysis, of which 606 (27.2%) underwent I-LND. Following adjustment, I-LND utilization was more likely in younger patients, those presenting with palpable adenopathy (cN1), treated in an academic facility, and those with a more contemporary diagnosis. On survival analysis, controlling for all known and measured confounders, I-LND receipt was associated with improved OS (HR 0.79 [CI 0.74–0.84], p < 0.001).

Conclusion:

In hospitals reporting to NCDB, the overall rate of I-LND for patients with invasive penile cancer was only 27.2%. Receipt if I-LND was associated with an increase in OS, justifying the use I-LND utilization as an important quality metric for performance reporting in patients with invasive penile cancer.

Keywords: Penile Cancer, Inguinal Lymphadenectomy, Utilization, Overall Survival, NCDB

Introduction:

Squamous cell carcinoma (SCC) of the penis is a rare condition diagnosed in approximately 1 in 100,000 men and accounts for less than 1% of cancers diagnosed in men in the US 1. Although rare, the disease carries significant morbidity and mortality with a 5-year cancer specific survival of approximately 50%. Given its rarity, the management of penile cancer has been based on small retrospective studies and consequently there is significant variation in the treatment of the disease.

Inguinal lymphadenectomy (I-LND) remains the most important staging and therapeutic intervention that can be performed in patients with invasive penile cancer2,3. Despite this, a recent population studies showed that in the US only 19% to 37% of patients with high grade or invasive penile disease undergo lymphadenectomy as recommended by the NCCN guidelines4,5. A major factor limiting the use of inguinal lymphadenectomy is the high risk of post-operative complications associated with the procedure6. Recent retrospective reports have shown the importance I-LND for patients with microscopic or low volume nodal disease; prompting the NCCN7 recommendation that I-LND be offered to any patient with high grade or invasive penile cancer (pT1b-T4), presenting with no or unilateral/low volume adenopathy (cN0-N1)7. For those with bilateral (cN2) or bulky (cN3) adenopathy the recommendation is for neoadjuvant chemotherapy followed by I-LND in select candidates7.

In this study, we aim to assess the utilization of inguinal lymphadenectomy (I-LND) in patients in whom I-LND is absolutely indicated per the NCCN guidelines ( high grade or invasive penile cancer (T1b-4) with minimal or no nodal involvement (N0/x-N1)), and assess the association between receipt of I-LND and overall survival using the National Base Cancer Database (NCDB).

Methods:

Data Source

The NCDB, a program of the ACS® CoC (Commission on Cancer) and the American Cancer Society, is a national cancer registry established in 1989 that serves as a comprehensive clinical surveillance resource for cancer care in the United States. The NCDB compiles data from more than 1,500 commission accredited cancer programs in the United States and Puerto Rico, and captures approximately 70% of all newly diagnosed cancer cases 8.

Definitions:

Cohort and primary outcome

Patients with penile squamous cell carcinoma were identified in the NCDB based on ICD-O-3 site and histology codes. Cases were selected based on squamous cell histology (8070 and 8071). Our study cohort included patients diagnosed between 2004 and 2014. Patients were selected based on invasive pathology defined as T1b-4, lack or unilateral low volume inguinal adenopathy (N0/x-N1), known surgical excision (partial or radical penectomy) and known lymph node procedure. Patients who died within 30 days of diagnosis, had clinical N2–3 nodal involvement or metastatic disease on presentation, did not receive treatment at the reporting hospital, or had a history of a prior malignancy were excluded from the study (Figure 1). In cases where pathological stage was not available clinical stage was used. To further limit any coding errors, only patients with a reported nodal count were included in the lymphadenectomy group, as well as excluding any patient with a lymph node count from the non-lymphadenectomy group. Our primary outcome measures were receipt of inguinal lymphadenectomy and overall survival.

Figure 1.

Figure 1.

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Consort Diagram Depicting Inclusion Criteria for the analyzed cohort

Covariates

Patients were evaluated using clinical, demographic, and pathologic characteristics available in the NCDB. Variables included patient characteristics such as year of diagnosis, age, race, Charlson-Deyo comorbidity classification 9, insurance status, median household income, and demographic location. Disease characteristics included pathological stage and grade, clinical and pathological nodal stage, and receipt of I-LND. Hospital characteristics included facility type and location.

Statistical Analysis

Temporal trends in the use of I-LND were assessed from 2004–2014 using Cochran-Armitage trend tests. We tested the association between I-LND and patient/tumor characteristics using Chi-squared tests. We then used multivariate logistic regression to simultaneously examine the association between all variables with the receipt of I-LND, accounting for within-hospital correlation with robust standard errors. Cox-proportional hazards regression analyses were then used to assess the impact of clinical and pathological variables on overall survival. We then conducted a propensity score weighted analysis 10 to assess the effect of I-LND in overall survival (OS). We estimated the propensity score via logistic regression, including all pre-treatment covariates, and using spline terms for age and year of diagnosis. Patients outside of the area of common support were dropped from the analysis, and we assessed balance after applying inverse probability weighting to the final cohort. We then used weighted Kaplan-Meier curves and a weighted Cox regression model to test the association between I-LND and survival. All statistical analyses were done with SAS version 9.4 and R version 3.33, with p <0.05 considered statistically significant.

Results:

We identified 2,224 men that met study inclusion criteria (Table 1). The cohort consistent mostly of older (median age 69), Caucasian (85.3%) men with a low comorbidity index (CCI 0: 65.7%). The majority of patients were treated in a comprehensive community (35.5%) or Academic/Research (45.9%) facility.

Table 1.

Sociodemographic and Clinical Characteristics of 2224 patients with pT1b-4 cN0/x-N1 Penile Squamous Cell Carcinoma

Patient Characteristic All Patients (%) I-LND (%) I-LND (%) p-value
Performed Not Performed
Age <0.001
 <50 233 10.5 99 42.5 134 57.5
 51–60 369 16.6 152 41.2 217 58.8
 61–70 539 24.2 171 31.7 368 68.3
 71+ 1083 48.7 184 17.0 899 83.0
Race 0.986
 White 1898 85.3 516 27.2 1382 72.8
 Black 231 10.4 64 27.7 167 72.3
 Other/Unknown 95 4.3 26 27.4 69 72.6
Hispanic 0.014
 No 1846 83.0 487 26.4 1359 73.6
 Yes 259 11.6 90 34.7 169 65.3
 Unknown 119 5.4 29 24.4 90 75.6
Charlson-Denyo Score 0.009
 0 1461 65.7 416 28.5 1045 71.5
 1 564 25.4 154 27.3 410 72.7
 2 199 8.9 36 18.1 163 81.9
Insurance Status <0.001
 Not Insured 162 7.3 60 37.0 102 63.0
 Private Insurance 553 24.9 193 34.9 360 65.1
 Medicaid 156 7.0 51 32.7 105 67.3
 Medicare 1268 57.0 268 21.1 1000 78.9
 Other Government 27 1.2 10 37.0 17 63.0
  Unknown 58 2.6 24 41.4 34 58.6
Median Income 0.489
 < 30,000 497 22.3 133 26.8 364 73.2
 30,000 – 34,999 625 28.1 173 27.7 452 72.3
 35,000 – 45,999 563 25.3 156 27.7 407 72.3
 46,000 + 513 23.1 141 27.5 372 72.5
 Unknown 26 1.2 3 11.5 23 88.5
High School Graduate 0.166
 29% or more 526 23.7 159 30.2 367 69.8
 20% - 28.9% 664 29.9 171 25.8 493 74.2
 14% – 19.9% 626 28.1 175 28.0 451 72.0
 < 14% 384 17.3 98 25.5 286 74.5
 Unknown 24 1.1 3 12.5 21 87.5
Demographic Location 0.036
 Large Metropolitan 955 42.9 286 29.9 669 70.1
 Small Metropolitan 690 31.0 166 24.1 524 75.9
 Suburban 307 13.8 87 28.3 220 71.7
 Rural 200 9.0 54 27.0 146 73.0
 Unknown 72 3.2 13 18.1 59 81.9
Facility Type* <0.001
 Community Cancer 194 8.7 24 12.4 170 87.6
 Comprehensive Community 762 34.3 113 14.8 649 85.2
 Academic/Research 984 44.2 389 39.5 595 60.5
 Integrated Cancer Network 206 9.3 42 20.4 164 79.6
Facility Location by Region* 0.269
 New England 149 6.7 26 17.4 123 82.6
 Mid Atlantic 307 13.8 82 26.7 225 73.3
 South Atlantic 486 21.9 127 26.1 359 73.9
 East North Central 380 17.1 103 27.1 277 72.9
 East South Central 199 8.9 61 30.7 138 69.3
 West North Central 167 7.5 44 26.3 123 73.7
 West South Central 188 8.5 54 28.7 134 71.3
 Mountain 87 3.9 19 21.8 68 78.2
 Pacific 183 8.2 52 28.4 131 71.6
Pathological T-Stage 0.070
 T1b 122 5.5 21 17.2 101 82.8
 T2 1354 60.9 371 27.4 983 72.6
 T3 703 31.6 200 28.4 503 71.6
 T4 45 2.0 14 31.1 31 68.9
Tumor Grade 0.364
 1 & 2 1520 68.3 428 28.2 1092 71.8
 3 & 4 619 27.8 156 25.2 463 74.8
 Unknown 85 3.8 22 25.9 63 74.1
Clinical Nodal Stage <0.001
 N0/x 2094 94.2 518 24.7 1576 75.3
 N1 130 5.8 88 67.7 42 32.3
Year of Diagnosis 0.001
 2004 129 5.8 30 23.3 99 76.7
 2005 151 6.8 33 21.9 118 78.1
 2006 165 7.4 38 23.0 127 77.0
 2007 188 8.5 46 24.5 142 75.5
 2008 196 8.8 42 21.4 154 78.6
 2009 196 8.8 57 29.1 139 70.9
 2010 215 9.7 63 29.3 152 70.7
 2011 226 10.2 60 26.5 166 73.5
 2012 228 10.3 76 33.3 152 66.7
 2013 248 11.2 67 27.0 181 73.0
 2014 282 12.7 94 33.3 188 66.7
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*

Missing information in 78 patients

606 (27.2%) men underwent lymphadenectomy over the study period (2004–2014). I-LND utilization showed a steady increased over the study period (Figure 2), with 33.6% of eligible patients receiving I-LND in 2014 compared to 23.3% in 2004 (p<0.001). When comparing patients who underwent an I-LND and those who did not, significant differences were seen with respect to age (<0.001), Hispanic ethnicity (p=0.014), Charlson-Deyo score (p=0.009), insurance status (p<0.001), Demographic location (p=0.036), treatment facility (p<0.001), and nodal status (p<0.001), as shown in Table 1.

Figure 2.

Figure 2.

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Graph depicting the percentage of patient with pTlb-4 cNO/x recieving Inguinal Lymaphenectomy (l-LND)

Following adjustment, I-LND was more likely to be performed in patients treated in an Academic/Research facility (OR 4.22 [CI 2.61–6.81], p < 0.001), presenting with palpable unilateral inguinal adenopathy (cN1) (OR 5.59 [CI 3.71–8.42], p < 0.001), and in those with a more contemporary diagnosis (OR 1.06 [CI 1.02–1.10], p< 0.001). In comparison, utilization of I-LND was less likely to occur with increased age (p <0.001), especially for those ≥ 71 years old (OR 0.41 [CI 0.27–0.62], p < 0.001) and those presenting with T1b pathology (OR 0.41 [CI 0.24–.071], p = 0.002). A similar but not statistically significant trend (p = 0.091) was seen in regards to worsening comorbidity, with those presenting with severe comorbidity (CCI-2) being less likely to receive I-LND than CCI-0 (OR 0.64 [CI 0.42–.098), p = 0.040), shown in Table 2.

Table 2.

Multivariate Regression Analysis for Receipt of Lymphadenectomy

Patient Characteristics OR 95% CI p-value
Age <0.001
 <50 Ref Ref Ref Ref
 51–60 1.15 0.78 1.71 0.470
 61–70 0.99 0.65 1.51 0.972
 71+ 0.43 0.29 0.65 <0.001
Race 0.076
 White Ref Ref Ref Ref
 Black 0.93 0.65 1.32 0.687
 Unknown/Other 0.59 0.37 0.94 0.025
Hispanic 0.962
 No Ref Ref Ref Ref
 Yes 1.05 0.74 1.50 0.788
 Unknown 1.02 0.63 1.64 0.940
Charlson-Denyo Score 0.091
 0 Ref Ref Ref Ref
 1 0.97 0.79 1.19 0.765
 2 0.64 0.42 0.98 0.040
Insurance Status 0.818
 Private Insurance Ref Ref Ref Ref
 Not Insured 0.91 0.61 1.36 0.657
 Medicaid 0.78 0.51 1.19 0.246
 Medicare 0.93 0.69 1.25 0.645
 Other Government 0.94 0.43 2.05 0.876
 Unknown 1.26 0.64 2.48 0.512
Median Income 0.655
 < 30,000 Ref Ref Ref Ref
 30,000 – 34,999 1.15 0.83 1.59 0.414
 35,000 – 45,999 1.19 0.85 1.66 0.318
 46,000 + 1.31 0.85 2.03 0.218
High School Graduate 0.474
 29% or more Ref Ref Ref Ref
 20% – 28.9% 0.87 0.63 1.21 0.411
 14% – 19.9% 1.05 0.74 1.49 0.795
 <14% 0.84 0.52 1.36 0.483
Demographic Location 0.489
 Rural Ref Ref Ref Ref
 Large Metropolitan 1.10 0.68 1.78 0.689
 Small Metropolitan 0.98 0.64 1.51 0.939
 Suburban 1.07 0.64 1.79 0.784
 Unknown 0.56 0.21 1.49 0.249
Facility Type <0.001
 Community Cancer Ref Ref Ref Ref
 Comprehensive Community 1.23 0.75 2.02 0.403
 Academic/Research 4.04 2.53 6.45 <0.001
 Integrated Cancer Network 1.75 0.93 3.27 0.082
Facility Location 0.384
 New England Ref Ref Ref Ref
 Mid Atlantic 1.19 0.68 2.10 0.538
 South Atlantic 1.58 0.90 2.77 0.110
 East North Central 1.14 0.63 2.08 0.671
 East South Central 2.21 1.10 4.43 0.025
 West North Central 1.16 0.57 2.35 0.684
 West South Central 1.38 0.72 2.65 0.329
 Mountain 1.23 0.54 2.79 0.623
 Pacific 1.63 0.90 2.97 0.107
Pathological T-Stage 0.005
 T2 Ref Ref Ref Ref
 T1b 0.41 0.24 0.71 0.002
 T3 0.93 0.75 1.15 0.500
 T4 0.65 0.33 1.28 0.211
Tumor Grade 0.421
 1 & 2 Ref Ref Ref Ref
 3 & 4 1.11 0.87 1.40 0.399
 Unknown 0.79 0.48 1.31 0.363
Clinical N-Stage <0.001
 N0 Ref Ref Ref Ref
 N1 5.59 3.71 8.42 <0.001
Year of Diagnosis 0.002
Trend from 2004–2014 1.06 1.02 1.11 0.001
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On survival analyses, increasing pathological stage (pT3: HR 1.22 [CI 1.06–1.40], p=0.006; pT4: HR 2.32 [CI 1.51–3.55], p<0.001), pN1 disease (HR 1.49 [CI 1.16–1.92], p=0.011) high grade disease (HR 1.46 [CI 1.27–1.69]. p < 0.001), increasing age (≥ 71) (HR 1.72 [CI 1.20–2.46], p = 0.003) and worsening comorbidity (CCI-1: HR 1.43 [CI 1.22–1.68] CCI-2: HR 1.91 [CI 1.52–2.39], p < 0.001 for both) were all associated with decreased survival. Receipt of I-LND (HR 0.59 [CI 0.48–0.72], p < 0.001) and Hispanic ethnicity (HR 0.68 [CI 0.51–0.92], p = 0.039) were both associated with improved survival, as shown in Table 3. Following propensity score adjustment, receipt of I-LND continued to show a survival benefit in the study cohort (HR 0.79 [CI 0.74–0.84], p < 0.001), as shown in Figure 3.

Table 3.

Cox Multivariate Regression Analysis for Overall Survival

Patient Characteristics HR 95% CI p-value
Age <0.001
 <50 Ref Ref Ref Ref
 51–60 0.97 0.68 1.38 0.843
 61–70 1.06 0.74 1.51 0.755
 71+ 1.72 1.20 2.46 0.003
Race 0.337
 White Ref Ref Ref Ref
 Black 1.19 0.93 1.51 0.165
 Unknown/Other 1.13 0.77 1.66 0.539
Hispanic 0.039
 No Ref Ref Ref Ref
 Yes 0.68 0.51 0.92 0.012
 Unknown 1.03 0.79 1.34 0.835
Charlson-Denyo Score <0.001
 0 Ref Ref Ref Ref
 1 1.43 1.22 1.68 < 0.001
 2 1.91 1.52 2.39 < 0.001
Insurance Status 0.964
 Private Insurance Ref Ref Ref Ref
 Not Insured 0.97 0.68 1.38 0.860
 Medicaid 1.05 0.74 1.48 0.794
 Medicare 1.06 0.87 1.29 0.558
 Other Government 1.19 0.62 2.26 0.604
 Unknown 0.88 0.54 1.42 0.599
Median Income 0.746
 < 30,000 Ref Ref Ref Ref
 30,000 – 34,999 0.89 0.71 1.11 0.311
 35,000 – 45,999 0.92 0.70 1.20 0.531
 46,000 + 0.95 0.70 1.30 0.767
High School Graduate 0.738
 29% or more Ref Ref Ref Ref
 20% – 28.9% 0.89 0.71 1.10 0.274
 14% – 19.9% 0.90 0.70 1.16 0.415
 <14% 0.93 0.69 1.25 0.627
Demographic Location 0.712
 Rural Ref Ref Ref Ref
 Large Metropolitan 0.92 0.70 1.21 0.551
 Small Metropolitan 0.85 0.66 1.09 0.206
 Suburban 0.89 0.66 1.19 0.415
 Unknown 0.90 0.59 1.37 0.627
Facility Type 0.572
 Community Cancer Ref Ref Ref Ref
 Comprehensive Community 1.15 0.90 1.48 0.266
 Academic/Research 0.89 0.69 1.15 0.365
 Integrated Cancer Network 1.06 0.76 1.48 0.745
Facility Location 0.272
 New England Ref Ref Ref Ref
 Mid Atlantic 1.19 0.86 1.64 0.306
 South Atlantic 1.35 0.98 1.84 0.063
 East North Central 1.46 1.06 2.00 0.019
 East South Central 1.39 0.96 2.00 0.081
 West North Central 1.26 0.87 1.80 0.220
 West South Central 1.13 0.77 1.67 0.533
 Mountain 1.56 1.06 2.30 0.024
 Pacific 1.28 0.88 1.85 0.193
Pathological T-Stage <0.001
 T2 Ref Ref Ref Ref
 T1b 0.89 0.58 1.34 0.5649
 T3 1.22 1.06 1.40 0.0063
 T4 2.32 1.51 3.55 < 0.001
Tumor Grade <0.001
 1 & 2 Ref Ref Ref Ref
 3 & 4 1.46 1.27 1.69 < 0.001
 Unknown 1.08 0.77 1.52 0.6482
Pathological N-Stage 0.002
 N0 Ref Ref Ref Ref
 N1 1.49 1.16 1.92 0.0018
Inguinal Lymphadenectomy <0.001
 No Ref Ref Ref Ref
 Yes 0.59 0.48 0.72 < 0.001
Year of Diagnosis 0.605
Trend from 2004–2014 1.01 0.98 1.04 0.6054
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Figure 3.

Figure 3.

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Kaplan-Meier survival curves of overall survival of penile cancer patients as function of receipt of lymphadenectomy after propensity score weighting

Discussion:

The impact of inguinal lymphadenectomy (I-LND) on the survival of patients with invasive penile cancer has been recognized as early as 1986 11. Despite the early evidence and numerous confirming retrospective studies 2,12, I-LND in the US remains underutilized4,5,13. The main hesitancy for the use of I-LND is the significant comorbidity associated with the procedure, which has a reported complication rate of 14%–37% 14,15. Despite strong recommendations in both the NCCN7 and EUA16 guidelines, the use of I-LND in patients with high grade or invasive penile cancer and cN0–1 disease remains controversial, mainly due to fear of overtreatment leading to the use of surveillance strategies and fine needle aspiration17,18 in the hope to improve patient selection. In this observational cohort, consisting of patients with an absolute indication for I-LND per NCCN guidelines (T1b-4 N0/x-1), I-LND was found to have significant impact on survival with a difference in median overall survival of 18.1 months (75.5 months (+) I-LND vs. 57.4 months (−) I-LND).

In our cohort, the rate of lymphadenectomy was calculated at 27.2% over a 10-year period. Although the rate is alarming low, these findings are consistent with those reported by Chippollini et al5 (NCDB) and Johnson et al13 (SEER), who using similar patient cohorts calculated comparable lymphadenectomy rates of 19.6% and 26.5%, respectively. Marginal I-LND utilization is not specific to penile cancer with vulvar cancer19 (20.4%) and lower extremity melanoma20 (39%) reporting similar sub-standard rates. Encouraging, was the increase use I-LND over the study period (Figure 2), which is likely related to less ambiguous recommendations with the introduction of treatment guidelines7,16, emphasis in centralization of care5,21 and the introduction of minimally invasive techniques geared towards improvement of post-operative complications 22

Utilization of I-LND was more likely to occur in younger patients (p < 0.001), those with a more contemporary diagnosis (p = 0.02), and those treated in an Academic/Research facility (p < 0.001). In contrast, I-LND utilization did not increase with worsening pathological stage, and the likelihood of receiving I-LND was decreased for those presenting with T1b lesions (OR 0.41 [CI 0.24–.071], p = 0.002). These findings are worrisome given numerous reports demonstrating the increased incidence of lymphoid metastases associated with lympho-vascular invasion23 and poorly differentiated cancers23, which are features that define T1b lesions per AJCC TNM staging system24. Furthermore, lymphadenectomy was more common for those presenting with clinically palpable adenopathy (cN1:73.9% vs cN0/x: 23.1%, p < 0.001), demonstrating an erroneous risk adapted approach given the far greater benefit seen in those with microscopic nodal disease25. Interestingly, comorbidity index (p = 0.079), median household income (p = 0.841), demographic location (p = 0.656), or education level (p = 0.738) had no effect in on I-LND utilization, which have been preconceived factors related to access to appropriate care in patients with penile cancer, who often present from rural, and underserved areas.

Similar observations were noted by Bilimoria et al20, when lymphadenectomy utilization was assessed in melanoma patients. Using the NCDB database, the authors demonstrated that utilization of lymphadenectomy decreased with advancing age, treatment in community versus academic/research facility and lesion location (lower extremities). As with penile cancer, increasing comorbidity, insurance type, household income, demographic location and race had no effect on lymphadenectomy utilization. Together, the data suggests that the low utilization of I-LND is likely related to physician experience and comfort rather patient factors; emphasizing the need to centralize care for those presenting with rare malignancies21,26. This is supported by a recent report in which the adherence to EAU penile guidelines was studied in an Italian population27; where the care of penile cancer patients is concentrated at eight tertiary care centers. The study showed that overall adherence to EUA guideline recommendations occurred in 66% of the cases, with an I-LND utilization rate of 70%.

Our survival analyses demonstrated that receipt of lymphadenectomy and Hispanic ethnicity were both associated with improved survival; whereas, increasing age, worsening comorbidity, higher pathological stage, high grade disease, and pathological nodal disease were all associated with decreased survival. Following adjustment for known confounders using propensity score weighting, receipt of I-LND continued to have a beneficial effect on overall survival (HR 0.79 [CI 0.74–0.84], p < 0.001). The above findings are of great importance as it validates the findings of several small retrospective reports 2,3,12 on the importance of I-LND in the survival of patients with invasive penile cancer using observational data from a large national cancer registry. Penile cancer remains one of the few disease processes, along with testis cancer 28, in which a modifiable factor such as lymphadenectomy is proven to provide a survival advantage. As such, we must emphasize the use of I-LND as an important quality metric for the management of patients with invasive penile cancer.

Despite its strengths our study is not devoid of limitations. First, large retrospective databases are prone to coding errors, which must be addressed carefully prior to data analysis. We attempted to control for coding errors by excluding patients with a reported lymph node procedure but no documented lymph node count; as well as, any patient with a lymph node count but no documented lymph node procedure. Given the alarming low rate of I-LND utilization calculated from the NCDB database (27.2%), one must wonder if this number represents a true practice representation versus a lack of data capture from the NCDB database. Lymphadenectomy procedures in penile cancer compared to other malignancies may present a coding issue for the NCDB as these procedures are usually performed in staged fashion. The NCDB database only tracks procedures performed in a COC-approved facility and those that pertain to the initial cancer treatment29 ; therefore, a staged lymphadenectomy performed in a non-COC facility or miss-categorize as a recurrence could potentially be left out by the coders leading to the under reporting of I-LND in the database. Despite, the role that miscoding or under reporting may have played in low I-LND rates reported using the NCDB database, the comparable rates reported using the SEER-Medicare13 warn of a possible practice phenomenon which we must continue to study if we hope to improve the care of penile cancer patients. Second, the use of the NCDB database may lead to sampling bias as the NCDB only queries records from CoC-approved facilities, which may affect the generalizability of our results. Review of other disease sites by Mettlin et al 30, has shown that patient and disease treatment characteristics between NCDB and SEER (a national representative sample) are comparable which may mitigate this bias. Third, the overall improvement on overall survival seen in patients receiving lymphadenectomy may be a function of younger and healthier patients undergoing the procedure. To minimize this potential bias in our survival analysis we used propensity adjustment to reduce impact of known confounding variables 10, however, it is possible that residual bias from unmeasured factors may remain. Finally, the NCDB database does not allow for assessment of patient choice on whether to undergo or forgo lymphadenectomy as part of their treatment plan. We attempted to reduce this bias by including only patients in whom a lymphadenectomy is an absolute indication (T1b-4 N0/x-1) in all existing best practice guidelines7,16.

Conclusion:

In hospitals reporting to NCDB, the overall rate of I-LND utilization for invasive penile cancer was only 27.2%. The use of I-LND saw a statistically significant increase over the study period from 23.3% in 2004 to 33.6% in 2014, which is encouraging. There was a significant increase in median overall survival in patients who received I-LND, justifying use of I-LND utilization an important quality metric for performance reporting in patients with invasive penile cancer.

Footnotes

Financial Sources: None

Conflicts of Interest: None

Andres F. Correa, MD: No financial disclosures, No Disclosures

Elizabeth Handorf, PhD: No financial disclosures

Shreyas S. Joshi, MD: No financial disclosures

Daniel M. Geynisman, MD: No financial disclosures

Alexander Kutikov, MD: No financial disclosures

David Y. Chen, MD: No financial disclosures

Robert G. Uzzo, MD: No financial disclosures

Rosalia Viterbo, MD: No financial disclosures

Richard E. Greenberg, MD: No financial disclosures

Marc C. Smaldone, MD, MSHP: No financial disclosures

Contributor Information

Andres F. Correa, Department of Surgical Oncology, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA; Department of Urology Creighton University, Omaha NE.

Elizabeth Handorf, Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia PA.

Shreyas S. Joshi, Department of Surgical Oncology, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA.

Daniel M. Geynisman, Department of Hematology and Oncology, Division Genitourinary Oncology, Fox Chase Cancer Center, Philadelphia PA.

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