Vincenzo Serretta

Open prostatectomy for benign prostatic enlargement in southern Europe in the late 1990s: a contemporary series of 1800 interventions.

OBJECTIVES Contemporary series of open prostatectomies from Western countries are rare. Frequently, the analysis of the outcome of open prostatectomy refers to old experiences or to series from developing countries. Any comparison with transurethral resection of the prostate can be invalidated by complications of open surgery because of the lack of an adequate healthcare system and technology. METHODS The Sicilian-Calabrian Society of Urology performed a retrospective study to assess the surgical management of benign prostatic hyperplasia in Sicily and Calabria in 1997 and 1998. A three-page questionnaire was sent to the 36 urologic units of these two Italian regions with more than 7.5 million inhabitants. RESULTS Twenty-six units (72.3%) replied. Of 31,558 patients treated for symptomatic benign prostatic hyperplasia, 5636 underwent surgery. Open prostatectomy (n = 1804) accounted for 32% of all surgical treatment. The median prostate volume was 75 cm(3) and the median serum prostate-specific antigen level was 3.7 ng/mL. The postoperative median hospitalization time was 7 days. Concomitant low urinary tract disease was present in 25% of the patients. Severe bleeding occurred in 11.6% of open prostatectomies. Blood transfusions were given in 8.2% of cases. Sepsis was reported in 8.6% of the patients. Reinterventions, within 2 years, mainly due to bladder neck stenosis, were reported in 3.6% of cases. CONCLUSIONS The results of the present survey provide a current picture of open prostatectomy. This procedure, even if performed nowadays and in Western countries, shows the same significant rate of early and late complications reported in the past or in less-developed countries.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Pure Squamous Cell Carcinoma of the Bladder in Western Countries

Introduction: Pure squamous carcinoma (SCC) is a rare entity in western regions. The management of SCC still remains similar to that of transitional carcinoma, although it is a different entity. A retrospective review can be helpful in understanding the biological behavior of this uncommon vesical tumour.Material and Methods: Nineteen consecutive cases of pure SCC of the bladder, not related to bilharziasis or spinal cord injury, are herein reported. Fifteen patients were submitted to radical cystectomy, combined with emasculation in 1 case and unilateral nephroureterectomy in another. Partial cystectomy was performed in 1 patient and transurethral resection followed by radiotherapy in 3 more cases. Involvement of prostatic urethra and upper urinary tract was evident in 9 (47.3%) and 5 patients (26.3%), respectively. Four patients were submitted to neoadjuvant chemotherapy and 1 to presurgical radiotherapy without any objective response. Adjuvant chemotherapy was performed in 3 patients. At a mean follow–up of 52 months, 6 patients (31.5%) are alive without any evidence of disease. SCC antigen was monitored in 5 patients. The possible role of this marker in bladder SCC is discussed.Conclusions: Invasion of the upper urinary tract and prostatic urethra seems more common in SCC than in transitional cell carcinoma. Distant metastases are rare. Most patients die after attempts of locoregional control of the tumor have failed. Extensive surgery is recommended. Preoperative radiotherapy should be considered since pelvic recurrences are the leading cause of progression in squamous cell carcinoma.

Urinary NMP22 for the Detection of Recurrence After Transurethral Resection of Transitional Cell Carcinoma of the Bladder: Experience on 137 Patients

OBJECTIVES To evaluate the nuclear matrix protein 22 (NMP22) test in the management of patients after transurethral resection (TUR) of recurrent transitional cell carcinoma of the bladder. METHODS The NMP22 test was performed in 137 patients: in 42 patients, a bladder recurrence was detected by cystoscopy and histologically confirmed; 95 patients were recurrence-free at cytology and cystoscopy performed at least 3 months after TUR. RESULTS In patients with tumoral recurrence, the mean NMP22 value was 54.8 U/mL. The false-negative rate was 28.5%. In recurrence-free patients, the mean NMP22 value was 22.8 U/mL. The specificity of the NMP22 test was 61%. Higher NMP22 mean values (29.6 versus 15.8 U/mL) were found in patients who underwent intravesical chemotherapy or immunotherapy. CONCLUSIONS Despite its good sensitivity, the NMP22 test cannot be adopted as a routine tool in the surveillance after TUR of patients with superficial bladder cancer because of its low specificity.

Urinary BTA–Stat, BTA–Trak and NMP22 in Surveillance after TUR of Recurrent Superficial Transitional Cell Carcinoma of the Bladder

Objectives: To evaluate NMP22, BTA–Stat and BTA–Trak tests in monitoring recurrent transitional cell carcinoma of the bladder.Methods: The tests were performed in 179 selected patients being followed up for recurrent superficial bladder tumors: 55 patients had bladder recurrence and 124 patients were recurrence free. The NMP22 test was obtained in all patients; BTA–Stat and BTA–Trak in the last 96 and 74 patients, respectively. Sixty–four patients (51.6%) were undergoing adjuvant intravesical chemotherapy.Results: Sensitivity was 74, 57 and 62% and specificity was 55, 62 and 79% for NMP22, BTA–Stat and BTA–Trak, respectively. A high percentage of patients submitted to intravesical chemotherapy had false–positive tests. Positive predictive values of the NMP22, BTA–Stat and BTA–Trak tests were 42.2, 40 and 45.4%, and negative predictive values were 82.9, 76.9 and 88.4%, respectively.Conclusions: NMP22, BTA–Stat and BTA–Trak tests cannot replace cystoscopy and cannot be adopted as routine tools in surveillance after TUR in patients with superficial bladder cancer.

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer

Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m2 week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory.

PSA reduction (after antibiotics) permits to avoid or postpone prostate biopsy in selected patients.

Microscopic foci of prostatitis may induce prostate-specific antigen (PSA) increase. PSA reduction after antibiotics might identify those patients in whom biopsy can be avoided. Ninety-nine patients received ciprofloxacin for 3 weeks, of whom 59 showed PSA reduction. Histology detected small foci of prostatitis in 65% of cases. Carcinoma was found in 40 and 20.3% of patients with unchanged or decreased PSA, respectively (P=0.03). No cancer was detected if PSA decreased below 4 ng/ml or more than 70%. Biopsy can be postponed, with a low risk of missing a cancer, if PSA decreases more than 70% or below 4 ng/ml.

Results of conservative treatment (transurethral resection plus adjuvant intravesical chemotherapy) in patients with primary T1, G3 transitional cell carcinoma of the bladder

OBJECTIVES To evaluate a selected population of 50 consecutive patients with primary T1, G3 bladder transitional cell carcinoma in the absence of carcinoma in situ (Tis) treated with a bladder-sparing approach. METHODS Between January 1983 and December 1992, all patients were treated by transurethral resection (TUR) plus adjuvant intravesical chemotherapy over 1 year. In most cases, doxorubicin, epirubicin, and mitomycin were used alone or in combination. RESULTS At a mean follow-up period of 52 months (range, 18 to 126), 16 of 50 patients (32%) showed a recurrent superficial tumor. The recurrent lesion was of Stage T1 in 11 (22%) cases, but was a T1, G3 tumor only in 5 cases (10%). In 2 additional patients (4%) a Tis developed during the observation period after TUR. The mean interval between TUR and first recurrence was 14.6 months (range, 3 to 38). At a mean time of 17 months after the initial TUR, 3 patients (6%) underwent a radical cystectomy due to a progression in T category and 3 additional patients (6%) developed distant metastases at a mean time of 23 months after TUR. In brief, 84% of the patients are alive and tumor-free. Five patients (10%) died of bladder cancer with a mean follow-up of 52 months. CONCLUSIONS If no concomitant Tis exist, a conservative approach is a legitimate option as an initial treatment of patients with primary T1, G3 bladder tumors.

PROSPECTIVE, RANDOMIZED, CROSSOVER COMPARISON OF SUBLINGUAL APOMORPHINE (3 mg) WITH ORAL SILDENAFIL (50 mg) FOR MALE ERECTILE DYSFUNCTION

PURPOSE We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel.

OBJECTIVE To investigate the activity and toxicity of metronomic chemotherapy with low-dose oral cyclophosphamide (CTX) and methotrexate (MTX) in patients with metastatic CRPC that progresses after docetaxel. Patients with castration-resistant prostate cancer (CRPC) that progresses after docetaxel may benefit from receiving further chemotherapy. METHODS Patients were treated with CTX 50 mg/d p.o. plus MTX 2.4 mg p.o. twice per week without rest periods. All patients received simultaneous luteinizing hormone-releasing hormone analogue. Prostate-specific antigen (PSA) response was defined as a 50% reduction on 2 evaluations at least 4 weeks apart. Objective response was measured according to the RECIST criteria. Pain relief was analyzed with the McGill-Melzack Pain Questionnaire. Simons 2-stage design for phase II study was used. Time to progression and progression-free and overall survival were computed. Toxicity was recorded according to the CTC-NCCN criteria. RESULTS A PSA decrease ≥50% was recorded in 15 of 58 evaluable patients (25%), and objective partial response in 3 (18%) and stable disease in 4 (24%) of 17 patients with measurable disease. Disease in 10 patients (59%) progressed. Pain intensity decreased in 16 (30%), increased in 18 (33%), and remained stable in 18 (33%) patients. Five patients discontinued narcotic analgesics for a mean duration of 12 weeks. Transitory grade 3 leukopenia was observed in 4 cases (7%), grade 3 thrombocytopenia in 2 (3%), and grade 2 anemia in 4 (7%). CONCLUSION This study demonstrates the feasibility, activity, and tolerability of oral low-dose CTX and MTX given on a metronomic schedule in patients with CRPC progressing after docetaxel-based chemotherapy.