Cathy Corbishley

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

Organ‐sparing surgery for invasive penile cancer: early follow‐up data

To present early outcome data from patients treated for invasive penile cancers with organ‐sparing surgery, as the treatment of such malignancies has traditionally either been amputative surgery or radical radiotherapy, both associated with significant physical and psychosexual morbidity.

Two-Center Evaluation of Dynamic Sentinel Node Biopsy for Squamous Cell Carcinoma of the Penis

PURPOSE Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve. PATIENTS AND METHODS All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated. RESULTS from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures. CONCLUSION Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.

Total glans resurfacing for premalignant lesions of the penis: initial outcome data

To report our initial experience of total glans resurfacing (TGR), as premalignant lesions of the glans penis have conventionally been treated by local excision, topical chemotherapy, laser or cryotherapy, but these techniques are frequently associated with high local failure rates and unsightly scarring that can make monitoring by gross inspection difficult.

Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated.

Study Type – Therapy (case series) Level of Evidence 4

Evaluation of dynamic lymphoscintigraphy and sentinel lymph-node biopsy for detecting occult metastases in patients with penile squamous cell carcinoma.

To evaluate the introduction of dynamic lymphoscintigraphy and sentinel lymph‐node (SLN) biopsy (used to detect occult lymph node metastases in patients with penile cancer and clinically impalpable inguinal lymph nodes at presentation) at a UK tertiary referral centre for penile cancer.

Molecular markers for predicting prostate cancer stage and survival

Objective To assess several molecular markers (detected by immunohistochemistry, IHC) to determine whether they can be used to improve the prognostic value of histological grade alone in predicting the behaviour of prostate cancer.

Prognostic Factors for Occult Inguinal Lymph Node Involvement in Penile Carcinoma and Assessment of the High-Risk EAU Subgroup: A Two-Institution Analysis of 342 Clinically Node-Negative Patients

BACKGROUND The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]). OBJECTIVE Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk. DESIGN, SETTING, AND PARTICIPANTS Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive. MEASUREMENTS The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo. RESULTS AND LIMITATIONS Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review. CONCLUSIONS Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection.

Dynamic sentinel lymph node biopsy in patients with invasive squamous cell carcinoma of the penis: a prospective study of the long-term outcome of 500 inguinal basins assessed at a single institution.

BACKGROUND Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary depending on whether results are reported per patient or per node basin, and with or without USS. OBJECTIVE To determine the long-term outcome of patients undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation in sensitivity of the procedure. DESIGN, SETTING, AND PARTICIPANTS A series of consecutive patients with newly diagnosed SCCp, over a 6-yr period (2004-2010), were analysed prospectively with a minimum follow-up period of 21 mo. All patients had definitive histology of ≥ T1G2 and nonpalpable nodes in one or both inguinal basins. Patients with persistent or untreated local disease were excluded from the study. INTERVENTION All eligible patients had DSNB and USS with or without FNAC of cN0 groins. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was no nodal disease recurrence on follow-up. The secondary end point was complications after DSNB. Sensitivity of the procedure was calculated per node basin, per patient, with DSNB alone, and with USS with DSNB combined. RESULTS AND LIMITATIONS Five hundred inguinal basins in 264 patients underwent USS with or without FNAC and DSNB. Seventy-three positive inguinal basins (14.6%) in 59 patients (22.3%) were identified. Four inguinal basins in four patients were confirmed false negative at 5, 8, 12, and 18 mo. Two inguinal basins had positive USS and FNAC and negative DSNB results. Sensitivity of DSNB with USS, with and without FNAC, per inguinal basin was 95% and per patient was 94%. Sensitivity of DSNB alone per inguinal basin and per patient was 92% and 91%, respectively. The DSNB morbidity rate was 7.6%. CONCLUSIONS DSNB in combination with USS has excellent performance characteristics to stage patients with cN0 SCCp, with a 5% false-negative rate per node basin and a 6% false-negative rate per patient.

Is the association between balanitis xerotica obliterans and penile carcinoma underestimated

To determine the incidence of balanitis xerotica obliterans (BXO) in a consecutive series of penile carcinomas in one centre, as BXO is a common penile disease that usually involves the prepuce and glans, and there have been sporadic case reports of the association between BXO and penile carcinoma, although it is uncertain if there is a specific causal relationship.