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  • 1
    Language: English
    In: The Journal of Urology, March 2014, Vol.191(3), pp.652-655
    Description: Routine followup of the groins of patients with penile squamous cell carcinoma after primary treatment consists of physical examination together with ultrasound of the groins, followed by fine needle aspiration cytology if suspicious. We assessed the value of this routine followup. Using ultrasound and fine needle aspiration cytology we assessed 247 patients during followup who were treated from 2004 to 2010 and underwent dynamic sentinel node biopsy only or observation of the inguinal regions. A negative result was defined as no evidence of metastatic disease after at least 2 years of followup. We calculated the sensitivity, specificity, and positive and negative predictive values of ultrasound and ultrasound guided fine needle aspiration cytology using standard statistical methods. Recurrence was diagnosed in 47 of 247 patients (55 groins). In 40 of 55 groins (73%) recurrence was detectable by physical examination. In 12 of 15 cases of nonpalpable recurrence (80%) ultrasound guided fine needle aspiration cytology revealed the recurrence. We considered 217 groins to be suspicious on ultrasound followed by fine needle aspiration cytology. Fine needle aspiration cytology revealed tumor in 49 groins and showed false-positive findings in 1 patient after negative completion lymphadenectomy. Sensitivity and specificity were 87.3% (48 of 55 cases) and 99.9% (1,304 of 1,305), respectively. Although inguinal recurrence manifests clinically in most patients, ultrasound guided fine needle aspiration cytology detected 80% of metastatic disease in patients with nonpalpable disease. Therefore, it has great value for detecting lymph node metastases during followup.
    Keywords: Penis ; Lymph Nodes ; Carcinoma ; Squamous Cell ; Biopsy ; Fine-Needle ; Ultrasonography ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 2
    Language: English
    In: The Journal of Urology, June 2015, Vol.193(6), pp.1976-1980
    Description: Pelvic lymph node involvement in penile cancer carries a poor prognosis. Therefore, there is controversy about the curative role of pelvic lymph node dissection. We analyzed the characteristics of tumor positive inguinal regions predictive for pelvic lymph node involvement in patients prophylactically treated with pelvic lymph node dissection. All chemonaïve consecutive cases treated with prophylactic pelvic lymph node dissection at our institution since 2001 were included in analysis. A generalized estimating equation model was used to predict pelvic node involvement based on inguinal characteristics. Disease specific survival was calculated with the Kaplan-Meier method. Included in study were 79 chemotherapy naïve patients without preoperative evidence of pelvic disease who were treated with prophylactic pelvic lymph node dissection. Pelvic nodes were positive in 24% of the patients. Inguinal extranodal extension, or 2 or more tumor positive nodes were predictive of tumor positive pelvic nodes. The 5-year disease specific survival rate in patients with pelvic involvement was 17%. Inguinal extranodal extension, or 2 or more inguinal tumor positive lymph nodes are predictive of pelvic tumor positivity in patients without evidence of pelvic involvement. However, disease specific survival remains poor in patients with pelvic node involvement who are treated with surgery only.
    Keywords: Penis ; Carcinoma ; Squamous Cell ; Lymph Nodes ; Neoplasm Metastasis ; Lymph Node Excision ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 3
    Language: English
    In: BJU International, 2015, Vol.116(5), p.734(10)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.12677/abstract Byline: Maxine Sun, Rosa S. Djajadiningrat, Hussain M. Alnajjar,Quoc-Dien Trinh, Niels M. Graafland, Nick Watkin, Pierre I. Karakiewicz, Simon Horenblas Keywords: 〈squamous cell carcinoma of the penis; prognostics; cancer-specific mortality; nomogram Objective To develop a novel postoperative prognostic tool, which attempts to integrate both pathological tumour stage and histopathological factors, for prediction of cancer-specific mortality (CSM) of squamous cell carcinoma of the penis (SCCP). Patients and Methods Patients with SCCP treated with inguinal lymph node dissection (ILND) or sentinel LN biopsy at a single institution were used for nomogram development and internal validation (n = 434), while a second cohort was used for external validation (n = 338). Multivariable Cox proportional hazards were used to examine the prognostic ability of patient age, a modified tumour staging that distinguishes between spongiosum and cavernosum body ingrowth tumours, a modified LN staging that integrates information on presence/absence of LN metastasis, extent of inguinal LN metastases, pelvic LN involvement, and extranodal involvement, and tumour grade. Model performance was quantified using measures of discrimination and calibration. Results Overall, 36% of patients had positive LN metastases (n = 156). In univariable analyses, the modified tumour and LN staging systems were statistically significantly associated with CSM, and remained in the final model with a discrimination of 89% within internal validation, and 95% within external validation. Calibration was nearly perfect. Conclusions The newly developed model integrates important prognostic factors, which existing models do not consider. Its performance was highly accurate using measures of discrimination and calibration.
    Keywords: Squamous Cell Carcinoma – Health Aspects
    ISSN: 1464-4096
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: The Journal of Urology, February 2015, Vol.193(2), pp.526-531
    Description: The incidence of penile cancer is increasing, and is suggested to be explained by changes in sexual practice and increased exposure of men to sexually transmitted high risk human papillomavirus infection. In penile cancers from a Dutch population treated in 1963 to 2001 we found a high risk human papillomavirus prevalence of about 30%. In this study we assessed the prevalence of high risk human papillomavirus-DNA in a more recent, contemporary penile cancer cohort and its association with patient survival. High risk human papillomavirus-DNA presence was assessed by GP5+6+ polymerase chain reaction in 212 formalin fixed, paraffin embedded invasive penile tumor specimens of patients treated between 2001 and 2009. The 5-year disease specific survival was calculated using the Kaplan-Meier method with the log rank test and Cox regression. High risk human papillomavirus-DNA was detected in a subset of penile cancer cases (25%, 95% CI 19–31). HPV16 was the predominant type, representing 79% (42 of 53) of all high risk human papillomavirus infections. The 5-year disease specific survival in the high risk human papillomavirus negative group and the high risk human papillomavirus positive group was 82% and 96%, respectively (log rank test p=0.016). Adjusted for stage, grade, lymphovascular invasion and age, human papillomavirus status was still prognostic for disease specific survival (p=0.030) with a hazard ratio of 0.2 (95% CI 0.1–0.9). High risk human papillomavirus-DNA was observed in a quarter of penile cancer cases. No relevant increase in high risk human papillomavirus prevalence in recent decades was observed. The presence of high risk human papillomavirus-DNA in penile cancer confers a survival advantage.
    Keywords: Penile Neoplasms ; Carcinoma ; Squamous Cell ; Human Papillomavirus 16 ; Survival ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 5
    Language: English
    In: The Journal of Urology, March 2017, Vol.197(3), pp.690-697
    Description: PD-L1 (programmed death ligand 1) inhibits T-cell function and prevents tumor eradication. This is facilitated by PD-L1 positive tumor cells and PD-L1 positive immune cells, and can be prevented by anti-PD-1 (programmed death 1)/PD-L1 immunotherapy. In advanced penile cancer there is a need for new therapeutic strategies. We investigated PD-L1 expression in penile cancers and compared PD-L1 expression with disease specific survival, lymph node metastases at diagnosis and high risk HPV status in a large patient cohort. A total of 213 primary tumors were immunohistochemically stained for PD-L1 and scored for tumor (percentage), stroma (binary) and PD-L1 positive tumor infiltrating macrophages. Additionally, PD-L1 positive tumors were scored for expression pattern, that is diffuse or predominantly present at the tumor-stroma margin. Staining was successful in 200 tumors, of which 75% were high risk HPV negative. Median followup was 62 months. Of 200 tumors 96 (48%) were PD-L1 positive (scored 1% or greater), of which 59 (62%) had a marginal expression pattern and 79 (82%) were high risk HPV negative (p = 0.03). Compared to PD-L1 negative tumors, the PD-L1 expression patterns had different prognostic values in the whole cohort as well as in the high risk HPV negative subgroup. On multivariable analyses a marginal expression pattern was associated with absent lymph node metastases (OR 0.4) while diffuse expression was associated with poor survival (HR 2.58). These results were more prominent in the high risk HPV negative subgroup (OR 0.25, HR 3.92). PD-L1 was expressed in 48% of penile carcinomas and mainly in high risk HPV negative tumors. The pattern of expression was a prognostic factor as marginal expression was associated with absent lymph node metastases and diffuse expression was associated with poor survival.
    Keywords: Penile Neoplasms ; Alphapapillomavirus ; Antigens ; Cd274 ; Tumor escape ; Survival Analysis ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 6
    Language: English
    In: The Journal of Urology, October 2014, Vol.192(4), pp.1105-1110
    Description: We assessed the impact of primary surgery, including penile sparing surgery vs (partial) penectomy and lymphadenectomy, on sexuality and health related quality of life. We invited 147 patients surgically treated for penile cancer at our institution between 2003 and 2008 to complete the IIEF-15, SF-36®, IOC (version 2) and questions on urinary function. We evaluated the impact of primary surgery type and lymphadenectomy on these outcomes. We also compared patient SF-36 scores with those of an age and gender matched normative sample from the general Dutch population. A total of 90 patients (62%) returned a completed questionnaire. Surgery type and extent were not associated significantly with most of the study outcomes assessed. However, men who underwent (partial) penectomy reported significantly more problems than those treated with penile sparing surgery, including orgasm (effect size 0.54, p = 0.031), appearance concerns (effect size 0.61, p = 0.008), life interference (effect size 0.49, p = 0.032) and urinary function (83% vs 43%, p 〈0.0001). Men who underwent lymphadenectomy reported significantly more life interference (effect size 0.50, p = 0.037). The patient sample scored significantly better than the normative sample on the SF-36 physical component (p = 0.044) and the bodily pain subscale (p 〈0.001). Few differences were observed in sexuality and health related quality of life as a function of primary surgery and lymphadenectomy. However, (partial) penectomy and lymphadenectomy were associated with more problems with orgasm, body image, life interference and urination. Additional longitudinal studies are warranted to evaluate individual changes with time in these outcomes.
    Keywords: Penis ; Carcinoma ; Squamous Cell ; Quality of Life ; Sexual Dysfunction ; Physiological ; Questionnaires ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 7
    In: BJU International, August 2015, Vol.116(2), pp.196-201
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.13009/abstract Byline: Jared M. Gopman, Rosa S. Djajadiningrat, Adam S. Baumgarten, Patrick N. Espiritu, Simon Horenblas, Yao Zhu, Chris Protzel, Julio M. Pow-Sang, Timothy Kim, Wade J. Sexton, Michael A. Poch, Philippe E. Spiess Keywords: complications; inguinal lymph node dissection; penile cancer Objectives To assess the potential complications associated with inguinal lymph node dissection (ILND) across international tertiary care referral centres, and to determine the prognostic factors that best predict the development of these complications. Materials and Methods A retrospective chart review was conducted across four international cancer centres. The study population of 327 patients underwent diagnostic/therapeutic ILND. The endpoint was the overall incidence of complications and their respective severity (major/minor). The Clavien-Dindo classification system was used to standardize the reporting of complications. Results A total of 181 patients (55.4%) had a postoperative complication, with minor complications in 119 cases (65.7%) and major in 62 (34.3%). The total number of lymph nodes removed was an independent predictor of experiencing any complication, while the median number of lymph nodes removed was an independent predictor of major complications. The American Joint Committee on Cancer stage was an independent predictor of all wound infections, while the patient's age, ILND with Sartorius flap transposition, and surgery performed before the year 2008 were independent predictors of major wound infections. Conclusions This is the largest report of complication rates after ILND for squamous cell carcinoma of the penis and it shows that the majority of complications associated with ILND are minor and resolve without prolonged morbidity. Variables pertaining to the extent of disease burden have been found to be prognostic of increased postoperative morbidity.
    Keywords: Complications ; Inguinal Lymph Node Dissection ; Penile Cancer
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 8
    Language: English
    In: The Journal of Urology, July 2014, Vol.192(1), pp.120-126
    Description: Management of squamous cell carcinoma of the penis changed in recent decades in favor of penile sparing surgery. We assessed whether penile sparing therapies were increasingly applied in our penile squamous cell carcinoma cohort with time and whether penile sparing affected 5-year cancer specific survival. We reviewed the records of 1,000 patients treated between 1956 and 2012, of whom 859 with invasive tumors were eligible for analysis. Tumors were staged according to the 2009 TNM classification. Binary logistic regression was used to assess penile preservation vs amputation with time. Cancer specific survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards model. Competing risk analysis was done for local recurrence. With time significantly fewer penile amputations were performed. The 5-year cumulative incidence of local recurrence as the first event after penile preservation was 27% (95% CI 23–32) while after (partial) penectomy it was 3.8% (95% CI 2.3–6.2, Gray test p 〈0.0001). Patients treated with penile preservation showed no significant difference in survival compared to patients treated with (partial) amputation after adjusting for relevant covariables. Factors associated with cancer specific survival were pathological T stage, pathological N stage and lymphovascular invasion on multivariable analysis. In the penile preservation group local recurrence as a time dependent variable in a Cox model was not associated with cancer specific survival (HR 0.52, 95% CI 0.21–1.24, p = 0.13). Significantly more penile preservation therapies were performed in more recent years. Although patients treated with penile preservation experienced more local recurrences, 5-year cancer specific survival was not jeopardized.
    Keywords: Penis ; Carcinoma ; Squamous Cell ; Amputation ; Organ Sparing Treatments ; Survival Analysis ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 9
  • 10
    In: BJU International, November 2015, Vol.116(5), pp.734-743
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.12677/abstract Byline: Maxine Sun, Rosa S. Djajadiningrat, Hussain M. Alnajjar,Quoc-Dien Trinh, Niels M. Graafland, Nick Watkin, Pierre I. Karakiewicz, Simon Horenblas Keywords: 〈squamous cell carcinoma of the penis; prognostics; cancer-specific mortality; nomogram Objective To develop a novel postoperative prognostic tool, which attempts to integrate both pathological tumour stage and histopathological factors, for prediction of cancer-specific mortality (CSM) of squamous cell carcinoma of the penis (SCCP). Patients and Methods Patients with SCCP treated with inguinal lymph node dissection (ILND) or sentinel LN biopsy at a single institution were used for nomogram development and internal validation (n = 434), while a second cohort was used for external validation (n = 338). Multivariable Cox proportional hazards were used to examine the prognostic ability of patient age, a modified tumour staging that distinguishes between spongiosum and cavernosum body ingrowth tumours, a modified LN staging that integrates information on presence/absence of LN metastasis, extent of inguinal LN metastases, pelvic LN involvement, and extranodal involvement, and tumour grade. Model performance was quantified using measures of discrimination and calibration. Results Overall, 36% of patients had positive LN metastases (n = 156). In univariable analyses, the modified tumour and LN staging systems were statistically significantly associated with CSM, and remained in the final model with a discrimination of 89% within internal validation, and 95% within external validation. Calibration was nearly perfect. Conclusions The newly developed model integrates important prognostic factors, which existing models do not consider. Its performance was highly accurate using measures of discrimination and calibration.
    Keywords: ≪Squamous Cell Carcinoma Of The Penis ; Prognostics ; Cancer‐Specific Mortality ; Nomogram
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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