Is there a role for neoadjuvant targeted therapy to downsize primary tumors for organ sparing strategies in renal cell carcinoma?

With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials.

[The foreskin and squamous-cell carcinoma of the penis]. / De voorhuid en het plaveiselcelcarcinoom van de penis.

The incidence of penile cancer is low in men who have been circumcised at infancy. It is unknown whether a causative relationship exists between circumcision and the substantially reduced incidence of penile cancer. A normal foreskin has no known aetiological role in the development of penile cancer. A narrow, non-retractable foreskin predisposes the patient to infection and contributes to the development of penile cancer, together with the known risk factors of smoking and human papillomavirus infection. Circumcision represents a complex of social and behavioural factors. Analyses have not taken all of these factors into consideration. It is unlikely that circumcision itself protects against the development of penile cancer.

[Less mutilating treatment of penile carcinoma]. / Minder mutilerende behandeling van het peniscarcinoom.

Four patients with penile carcinoma are described. A 60-year-old man with a T1-tumour underwent penis-conserving laser treatment. Two men, aged 52 and 65 years old, with T2-tumors and clinically node-negative groins underwent penile amputation. Sentinel-node biopsy (SNB) revealed no metastases in the 52-year-old patient. High-resolution ultrasound-guided fine-needle aspiration cytology revealed bilateral metastases in the other patient, who underwent bilateral inguinal lymphadenectomy. In the fourth patient, a 73-year-old man with a T3-tumor, a pathological lymph node was palpated in one groin. Inguinal lymphadenectomy revealed 3 positive nodes and an additional pelvic lymphadenectomy was performed. SNB on the other side was positive and inguinal lymphadenectomy followed. No additional positive nodes were found in the dissection specimen. All patients were alive without evidence of disease 4, 3, 3 and 4 years later, respectively. New developments in the management of penile cancer such as laser treatment, high-resolution ultrasonography and SNB result in a more tailored approach with less morbidity without reducing survival rates.

Morbidity of dynamic sentinel node biopsy in penile carcinoma.

PURPOSE: We report on the morbidity of dynamic sentinel lymph node biopsy (DSNB) in penile squamous cell carcinoma (SCC). MATERIALS AND METHODS: Between 1994 and 2003 DSNB was performed in 129 patients with T2 or T3 penile SCC who had 243 clinically node negative groins. Patients with groins with a tumor positive sentinel node underwent additional standard inguinal lymphadenectomy. RESULTS: A total of 285 sentinel nodes were harvested in 223 explored groins. The sentinel nodes were tumor-free in 189 groins. A total of 34 standard inguinal lymphadenectomies were performed because of a tumor positive sentinel node. There were 6 regional relapses during a median followup of 50 months (range 5 to 124) resulting in a false-negative rate of 15% (6 of 40 groins). This rate was 17% when calculated per patient (6 of 35 patients). Early and/or late complications following DSNB only occurred in 7% (14 of 189) of the groins. After DSNB followed by a standard inguinal lymphadenectomy, the rate was 68% (23 of 34). All complications of DSNB were minor and easily managed. CONCLUSIONS: Morbidity of DSNB in penile SCC is low. However, an in field recurrence after a negative DSNB is perhaps the greatest complication of the procedure.

Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases.

PURPOSE: In this retrospective study we compared the clinical outcome of early vs delayed excision of lymph node metastases in patients with penile squamous cell carcinoma. MATERIALS AND METHODS: A total of 40 patients with a T2-3 penile carcinoma with lymph node metastases were included in this study. All patients initially presented with bilateral impalpable lymph nodes. In 20 patients (50%) metastases were removed when they became clinically apparent during meticulous followup (median interval 6 months, range 1 to 24). There were 20 patients (50%) who underwent resection of inguinal metastases detected on dynamic sentinel node biopsy before they became palpable. The histopathological characteristics of the tumors and lymph nodes were reevaluated. RESULTS: The 2 populations were similar in terms of patient age, T-stage, pathological tumor grade, vascular invasion and infiltration depth. Disease specific 3-year survival of patients with positive lymph nodes detected during surveillance was 35% and in those who underwent early resection, 84% (log rank p = 0.0017). In multivariate analysis early resection of occult inguinal metastases detected on dynamic sentinel node biopsy was an independent prognostic factor for disease specific survival (p = 0.006). CONCLUSIONS: Early resection of lymph node metastases in patients with penile carcinoma improves survival.

How to avoid false-negative dynamic sentinel node procedures in penile carcinoma.

PURPOSE: Evaluation of the false-negative dynamic sentinel node procedures in penile carcinoma at our institute. MATERIALS AND METHODS: Between January 1994 and February 2003, 123 patients with penile squamous cell carcinoma underwent dynamic sentinel node biopsy. RESULTS: The sentinel node revealed metastasis in 28 (23%) of 123 patients. Regional recurrence after excision of a tumor-negative sentinel node or after nonvisualization was seen in 6 patients resulting in a false-negative rate of 18% (6 of 34). We assume that 1 false-negative case was due to tumor blockage, 3 to tumor blockage and rerouting, 1 to a pathological sampling error and 1 to a low radioactivity level in the sentinel node during surgery. CONCLUSIONS: Based on the false-negative results, important adaptations have been made in the dynamic sentinel node biopsy procedure for penile carcinoma at our institute. Pathological analysis was extended by serial sectioning and immunohistochemical staining, and preoperative ultrasonography with fine needle aspiration cytology has been added. Furthermore, exploration of groin without visualized sentinel nodes and intraoperative palpation of the wound have been introduced.