Reproducibility of histopathologic tumor grading in penile cancer—results of a European project

Abstract

Since reliable molecular prognostic parameters for inguinal lymph metastases in penile cancer are not available, tumor grading is often used as a surrogate prognostic tool for the indication of inguinal lymphadenctomy and has been integrated into the current TNM classification for penile cancer. The reliability of tumor grading is under discussion. We examined interobserver grading variability in 90 primary penile carcinomas, assessed by 12 different uropathologists from five European countries. Tumor grading, following the CAP scheme, was compared, and interobserver variability was calculated using kappa statistics. The interobserver variability was high as reflected by an overall low kappa coefficient (mean k = 0.34) and reached a moderate level only in 26.4 % of the cases (range 0.02-0.67). The percentage of G1 tumors assigned ranged from 8.6 to 52.5 %, G2 tumors from 27.1 to 72.6 % and G3 tumors from 11.7 to 48.7 %. Only some observers assigned G4 with a range of 0.6-21.9 %. Subdivision into low and high grade according to UICC and EAU classifications differed significantly (P < 0.001). Low reproducibility of grading in penile carcinomas with the favored method does not allow a reliable prognostication of tumor aggressiveness. Inclusion of histological grading into the TNM classification currently seems not to be a benefit.

The role of histologic subtype, p16INK4a expression, and presence of human papillomavirus DNA in penile squamous cell carcinoma

“…This is in line with some previous studies that failed to confirm a proposed association between histopathologic grade and lymph node metastasis or overall survival in pSCC, while it has to be stated as a clear limitation of our study that follow-up data was only obtainable for 35 patients (60.3%) [ 38 - 40 ]. Considering the substantial interobserver variability that has been described for histopathologic grading in pSCC (between 59-87% with ĸ = 0.38-0.69 [ 41 ]), we think that the current histopathologic grading is of limited value due to an obvious lack of prognostic relevance; this conclusion is also supported by other authors [ 42 ]. For the presence of HR-HPV we observed a trend towards better prognosis that failed to reach statistical significance; further investigations in larger cohorts might therefor be indicated.…”

DaPeCa‐1: diagnostic accuracy of sentinel lymph node biopsy in 222 patients with penile cancer at four tertiary referral centres – a national study from Denmark

“…Three of these patients developed inguinal metastases during follow‐up and all three eventually died from penile cancer. Comparison between penile cancer studies’ T‐ and G‐features is challenged by a high degree of inter‐observer variability, even between dedicated specialist uro‐pathologists (κ = 0.34), as discussed in a recent European collaborative study . This inter‐observer variability and possible relative under‐staging might explain the clinical outcome of the above‐mentioned seven T1G1 patients.…”

The Diagnosis and Treatment of Penile Cancer

“…Grading is more difficult with squamous cell carcinomas compared to adenocarcinomas. This explains the high interobserver variability in the grading of penile cancer (8). Consequently, there is no definitive prognostic difference between G1 and G2 in penile cancer, especially since highly differentiated penile squamous cell carcinomas can show invasive growth and metastatic spread, too.…”