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penile cancer

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Nick Watkin
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Historically penile cancer has been treated by partial or total penectomy. More recently, conservative techniques have evolved to preserve function, cosmesis and psychological well-being. The oncologic safety of these innovations needs to be compared with the more radical ablative strategies. We conducted an extensive review of the literature of penile preserving and ablative techniques and report on the oncological as well as functional outcomes. There were no randomized studies comparing preserving and ablative techniques. The majority of studies consisted of retrospective cohorts. The quality of evidence is level 3 at best. Cancer specific survival is similar in penis preserving and ablative approaches for low stage disease. Penile preservation is superior in functional and cosmetic outcomes and should be offered as a primary treatment modality in men with low stage penile cancer.
Nick Watkin
added 2 research items
In this article, the authors outline a contemporary management algorithm for penile cancer, with emphasis on developments in organ‐sparing surgical techniques and inguinal lymph node detection and management. Copyright © 2013 John Wiley & Sons
Nick Watkin
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ABSTRACT: Context: Management of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men. Objective: To undertake a systematic review of the evidence on AIRT in node-positive men with PSCC. Evidence acquisition: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken. Evidence synthesis: A total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p > 0.05). Conclusions: The evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice. Patient summary: Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.
Nick Watkin
added 2 research items
To develop a novel postoperative prognostic tool, which attempts to integrate both pathological tumor stage and histopathological factors for prediction of cancer-specific mortality (CSM) for SCCP. Patients with SCCP treated with inguinal lymph node dissection (ILND) or sentinel node 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 tumor staging that distinguishes between spongiosum and cavernosum body ingrowth tumors, a modified nodal staging that integrates information on presence/absence of lymph node metastasis, extent of inguinal metastases, pelvic nodal involvement, and extranodal involvement, and tumor grade. Model performance was quantified using measures of discrimination and calibration. Overall, 36% of patients had positive lymph node metastases (n=156). In univariable analyses, the modified tumor and nodal 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. 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.
Premalignant penile lesions are a difficult group of disorders to accurately differentiate from benign dermatoses. There is often a history of self-management or management in non-specialist centres leading to a delay in diagnosis. Early recognition and treatment of these lesions may prevent progression to invasive cancer thereby reducing the need for more traumatic interventions. It is important to note that penile cancer is a relatively rare malignancy affecting approximately 1 in 100,000 men per year in Europe and the USA, with premalignant lesions forming a small proportion of new cases. Therefore, the knowledge base relating to the management of premalignant lesions is often from small series or case reports. © Springer Science+Business Media New York 2014. All rights are reserved.
Nick Watkin
added 6 research items
Objectives To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). Methods Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George’s Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively. PIK3CA RNA expression was quantified using TaqMan gene expression assay. HPV DNA was detected with INNO-LiPA assay. p-AKT and p-mTOR protein expression were assessed using western blot and immunohistochemistry. Results PIK3CA copy number gain was found in 11/23 (48%) patients, with mutations present in only 2/24 (8%) patients. In comparison to NPE, PSCC showed significantly lower PIK3CA RNA expression (p=0.0007), p-AKT (Ser473) nuclear immunoexpression (p=0.026) and protein expression of p-AKT (Thr308) (p=0.0247) and p-mTOR (Ser2448) (p=0.0041). No association was found between PIK3CA CNS and p-AKT and p-mTOR protein expression. Conclusion Based on our results the PI3K-AKT-mTOR pathway is not a key driver in PSCC carcinogenesis and the therapeutic targeting of this pathway is unlikely to produce significant clinical benefit.
Background Organ sparing surgery (OSS) in the treatment of penile squamous cell cancer (SCCp) is well established. A 5 mm margin has previously been considered oncologically safe. Objective To evaluate the significance of close surgical margins in OSS and clinico‐pathological factors that may influence local recurrence. Patients and Methods At our tertiary referral centre, between March 2001 and September 2012, 332 patients treated with OSS for SCCp had clear surgical margins. As the focus was the impact of close clear margins on local recurrence, patients with positive margins were excluded for the purpose of this study. Our overall positive margin rate for OSS in penile cancer is 7.6% (42 patients). Analysis was carried out on an on‐going prospective database, including prospective accurate pathological recording of surgical margins. Patients underwent OSS following multidisciplinary team discussion. Local recurrence was the primary outcome measured and Fisher's exact test and time to recurrence curves were used in analysis. All local recurrences were scrutinised by the MDT and were categorised into true recurrences or metachronous new occurrences (i.e. tumours arising from a background of PeIN and forming on an epithelial surface not related to the site of initial resection). A multivariate analysis was also conducted to elucidate other factors influencing local recurrence. Results 64% had < 5mm clear deep surgical margin with 16% clear by <1mm. Overall, 4% of patients had a true local recurrence, with a median time to recurrence of 6 months. 53% were due to embolic spread, with residual occult local disease accounting for 47%. There was a statistically significant relationship between cavernosal involvement (p = 0.014), lymphovascular invasion (p = 0.001) and local recurrence. Although multivariate analysis revealed that the extent of clear margin was not a predictor of disease (p=0.405), we observed an increased risk of local recurrence in the clear margin cohort of <1mm compared to those of >1mm (p=0.0003). Those patients considered to have metachronous tumours were scrutinised by our multidisciplinary panel, and 8 patients (2.4%) were found to have new occurrences. Our overall proportion of patients therefore needing further treatment for either new occurrences or recurrent disease following OSS stands at 6.4%. Conclusions Overall the presence of local recurrent disease in OSS in our experience is low (4%). We report an embolic mechanism of local recurrence, strongly suggested by the presence of cavernosal involvement and lymphovascular invasion. We conclude that a deep clear margin of greater than 1mm has a very low risk of local recurrence in organ sparing surgery. This article is protected by copyright. All rights reserved.
Nick Watkin
added 2 research items
Introduction Nodal involvement is the most important prognostic factor in patients with squamous cell carcinoma of the penis (SCCp). However, optimal staging of regional lymph node remains controversial. Methods The literature was reviewed to examine current management of regional lymph nodes in SCCp patients with clinically nonpalpable inguinal lymph nodes (cN0). Results Radiological staging and selective risk-profile nomograms are unreliable in the detection of occult micrometastases in cN0 patients. Prophylactic inguinal lymph node dissection (ILND) is associated with significant morbidity and a high rate of postoperative complications. Dynamic sentinel lymph node biopsy (DSNB) is a reliable minimally invasive surgical staging technique for cN0 patients. Ipsilateral ILND is indicated only in inguinal basins with positive DSNB. Conclusions DSNB has excellent performance characteristics in staging cN0 patients, with high sensitivity and a low morbidity rate.
Context: Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. Objective: To provide an evidence-based update of treatment recommendations based on the literature published since 2008. Evidence acquisition: A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. Evidence synthesis: Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. Conclusions: Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. Patient summary: Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended.
Nick Watkin
added 6 research items
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of surgical interventions for localised penile cancer. The comparisons of interest are: one type of surgery versus another; surgical treatment versus non-surgical treatment.
Nick Watkin
added 3 research items