The chemoradiation therapy protocol is an alternative primary treatment modality for invasive urethral carcinoma. It enables an unprecedented potential for organ preservation.

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OBJECTIVE To evaluate PP2 as a modulator of the cadherin/catenin complex in late‐stage bladder carcinoma cells, and to assess its potential invasion‐suppressor activity in this model. MATERIALS AND METHODS A panel of five human bladder carcinoma cells, characterizing late‐stage disease, was used to determine the concentration for 50% inhibition of PP2 in cell‐proliferation assays. Modulation of cadherin/catenin expression by PP2 was determined in Western blot analysis, with an assessment of the activation status of mitogen‐activated protein kinase and Akt signalling pathways. Altered invasive capacity linked to these variables was determined in standard in vitro invasion assays. RESULTS PP2 elicited concentration‐dependent growth inhibition in all bladder cell lines within the panel, with growth suppression recorded at 10–35 µmol/L PP2. Distinct morphological changes were recorded in cell lines exposed to PP2, accompanied by up‐regulation of plakoglobin expression in a subset of lines. Exposure of cells to PP2 resulted in inactivation of Akt in all cells and a concomitant reduction in in vitro invasive capacity. CONCLUSIONS These results show that PP2 inhibits bladder carcinoma cell growth and can modulate plakoglobin expression in a subset of cell lines. In addition, PP2 can suppress the in vitro invasive capacity of bladder carcinoma cells by modulating the activation status of Akt.

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Invasive carcinoma of the male urethra is an aggressive tumor with dismal survival. Patients with this diagnosis are faced with disfiguring surgery and overall poor outcome. We present a series of patients treated with the modified Nigro chemo-radiation protocol as a primary therapeutic modality.METHODS: Between January 1991 and September 2004, 14 patients with invasive carcinoma of the urethra were managed with a modified Nigro chemoradiation protocol. Thirteen patients had squamous cell carcinoma and one had adenocarcinoma of the urethra. The pendulous urethra was the origin in 5 patients and in 9 patients the bulbo-membranous urethra was the primary site of cancer. Presenting symptoms in patients included a history of urethral strictures in 8, painful mass in I, penile ulceration in 2, lower urinary tract symptoms (dysuria) and pain in 3. Initial evaluation included retrograde urethrogram , cystourethroscopy with urethral biopsy and CT scan of the chest and abdomen. Clinical stage was T2NO in I, T2N2 in I, T3NO in 6, T3Nl in I , T3N2 in I, and T4NO in 4. The initial treatment was by suprapubic cystotomy urinary diversion. The modified chemo-radiation regimen consisted of 45 Gy in 25 fractions over 35-45 days. Radiation was administered to the primary site and to bilateral groin areas. Concurrently, mitomycin (10mg/m2) was given on day one, continuous infusion of 5FU (I 000mg/m2/24 hrs) was also administered starting on day one and continued for 4 days. The chemotherapy cycle was repeated 28 days later, usually starting on the last 4 days of the radiation cycle. Local recurrence was evaluated by performing serial physical examinations and cystourethroscopy with repeat biopsy. Radiological examination included CT scan of the abdomen and pelvis.RESULTS: No evidence of local recurrence was noted in 12 patients, consistent with a disease specific survival rate of 85. 7%. One patient died of metastatic disease. Two patients had local recurrence. Of these, one death occurred at 15 months. This patient had a pendulous lesion. He underwent surgical excision and adjuvant chemotherapy. The other local non-responder, underwent radical surgical resection and reconstruction and is currently NED at 7 years. Urethral stricture resulted in 8 survivors with urethral reconstruction performed in 4 patients.CONCLUSIONS: The modified Nigro chemo-radiation protocol is an alternative primary treatment modality for invasive urethral carcinoma with genital preservation and increased survival rates.