Prognosis of the 8th TNM Staging System for Penile Cancer and Refinement of Prognostication by Incorporating High Risk Human Papillomavirus Status

Wang, Beihe; Gu, Weijun; Wan, Fangning; Yu, Wei; Xiao, Wenjun; Lü, Xiaolin; Zhang, Guiming; Zhou, Jian-Lan; Wang, Qifeng; Ding, Xuefei; Azizi, Mounsif; Spiess, Philippe E.; Ye, Ding Wei; Zhu, Yao

doi:10.1097/ju.0000000000000584

Cited by 25 publications

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“…Our study did not analyze the association between the prognosis and HPV prevalence, because the median follow-up time was too short. A recent published international multicenter study including 230 patients in our study found HPV status could separate the prognosis of pN2-3 patients, and pN2-3 high risk HPV negative group was associated with only 32% 5-year survival (19).…”

Section: Discussionsupporting

confidence: 49%

Importance of HPV in Chinese Penile Cancer: A Contemporary Multicenter Study

Zhang

et al. 2020

Front. Oncol.

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Objective: To investigate the HPV DNA prevalence and genotype distribution among penile cancer in China. To identify association between HPV prevalence, different histological subtypes, tumor stage, tumor grade, demographics, comorbidity, and phimosis incidence trend. Standardized HPV DNA detection and p16 INK4a expression were used in a multi-center series of 340 penile squamous cell carcinomas diagnosed from 2006 to 2017. Materials and Methods: HPV DNA detection and genotyping were examined by a validated kit for 23 different HPV subtypes (PCR-RDB HPV test). The cases with positive HPV DNA were additional tested for p16 INK4a expression to confirm the HPV infection. Results: Using the PCR-RDB HPV test, overall HPV prevalence was 48.8% (166/340) and that of p16 INK4a expression was 45.6%. In this studied population, HPV16 was the most frequent HPV type detected in HPV-positive cancers (76.5%). HPV18 was the second most common type in penile cancers (15.1%). After pathology review, 307 cases were confirmed as invasive penile cancer, and the other 33 were non-invasive caners. The histologic subtypes of warty, basaloid, clear cell papillary, adenosquamaous and pseudohyperplastic were showed high HPV DNA prevalence. Among invasive cancers, no statistically significant differences in prevalence were observed by tumor grade, tumor stage or lymphnode stage at diagnosis. HPV positive penile cancer incidence significantly increase and the phimosis incidence significantly decrease from 2006 to 2017. Conclusions: About a half of penile cancers were related to HPV infection. Our findings highlight the phimosis related penile cancers have been declining, the HPV related in the development of penile cancer and a fully aware of regional differences in HPV genotype distribution are tasks for penile cancer control and prevention.

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Section: Discussionsupporting

confidence: 49%

Importance of HPV in Chinese Penile Cancer: A Contemporary Multicenter Study

Zhang

et al. 2020

Front. Oncol.

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“…At the same time, PD‐L1 status and TMB are not ready to be implemented in routine clinical practice, and certainly are a lot more costly than easy‐to‐use, readily accessible risk stratification tools based on routinely available clinical data. Third, despite the eighth edition of the AJCC Staging Manual now being available [31], TNM staging could not be retrospectively updated for our study population. Fourth, there was a non‐negligible difference in the ILNM ratio, pathological stage, positive surgical margin rates, and rates of adjuvant therapy between the development and validation cohorts.…”

Section: Discussionmentioning

confidence: 99%

A risk calculator predicting recurrence in lymph node metastatic penile cancer

et al. 2020

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To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and Methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN 3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

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“…Li et al 27 proposed to include LVI as a major factor separating T2 and T3 based on their data. Wang et al 29 proposed to include HPV status as an stratification factor. In multicenter study including 230 patients, the authors found that HPV status could separate the prognosis of pN2-3 patients, and pN2-3 high-risk HPV negative group was associated with only 32% 5-year survival.…”

Section: Pt2: Tumor Invades Into Corpus Spongiosum (Either Glans or V...mentioning

confidence: 99%

“…indicator and it has been suggested for future changes in the staging manual. 29 However, a recent study from centers in Germany and Russia did not find HPV status to be an independent prognostic factor. 16 More than geographic differences, it may be that treatment modalities may account for the variation in the reports.…”

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confidence: 94%

What Is New in the Pathologic Staging of Penile Carcinoma in the 8th Edition of AJCC TNM Model: Rationale for Changes With Practical Stage-by-stage Category Diagnostic Considerations

Sánchez

Fernández‐Nestosa

Cañete‐Portillo

et al. 2021

Advances in Anatomic Pathology

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For > 50 years the tumor, node, metastasis (TNM) classification model of malignant tumors has been the main resource for clinicians, pathologists, radiologists and public health professionals ensuring a homogeneous classification and patients' management based on common staging and prognosis factors. Penile cancer was first included for staging in the third edition of the TNM classification with several changes in the last version, the 8th edition of the AJCC TNM Manual, in 2017. Some changes in the pT category were done due to recent knowledge regarding the prognostic importance of anatomical level of invasion, vascular and perineural invasion and tumor grading. These changes must be interpreted in the light of a required understanding of the complex anatomy of penile compartments especially their histological boundaries, the morphological differences of each level needed for the correct classification, the heterogeneity of penile squamous cell carcinomas and an adequate criticism of the current model used by the TNM system. We present here a series of stage-by-stage category diagnostic considerations based on the clinical experience acummulated over the years of applying the different TNM staging classifications in our large clinical practice. Some discrepancies will need welldesigned prospective studies for im4proving the actual classification.

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Prognosis of the 8th TNM Staging System for Penile Cancer and Refinement of Prognostication by Incorporating High Risk Human Papillomavirus Status

Cited by 25 publications

References 0 publications

Importance of HPV in Chinese Penile Cancer: A Contemporary Multicenter Study

Importance of HPV in Chinese Penile Cancer: A Contemporary Multicenter Study

A risk calculator predicting recurrence in lymph node metastatic penile cancer

What Is New in the Pathologic Staging of Penile Carcinoma in the 8th Edition of AJCC TNM Model: Rationale for Changes With Practical Stage-by-stage Category Diagnostic Considerations

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