Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

EAU Guidelines on benign prostatic hyperplasia (BPH).

OBJECTIVE: To establish guidelines for the diagnosis, treatment, and follow-up of BPH. METHODS: A search of published work was conducted using Medline. In combination with expert opinions recommendations were made on the usefulness of tests for assessment and follow-up: mandatory, recommended, or optional. In addition, indications and outcomes for the different therapeutic options were reviewed. RESULTS: A digital rectal examination is mandatory in the assessment for the diagnosis of BPH. Recommended tests are the International Prostate Symptom Score, creatinine measurement (or renal ultrasound), uroflowmetry, and postvoid residual urine volume. All other tests are optional. The aim of treatment is to improve patients' quality of life, and it depends on the severity of the symptoms of BPH. The watchful waiting policy is recommended for patients with mild symptoms, medical treatment for patients with mild-moderate symptoms, and surgery for patients who failed medication or conservative management and who have moderate-severe symptoms, and/or complications of BPH which require surgery. Regarding non-surgical treatments, transurethral microwave thermotherapy is the most attractive option. These treatments should be reserved for patients who prefer to avoid surgery or who no longer respond favourably to medication. Finally, recommendations for follow-up tests and a recommended follow-up time schedule after BPH treatment are provided. CONCLUSIONS: Recommendations for assessment, possible therapeutic options, and follow-up of patients with BPH are made.

Transurethral electrovaporization of the prostate vs. transurethral resection. Results of a multicentric, randomized clinical study on 150 patients.

AIM OF THE STUDY: To evaluate clinical, urodynamic efficacy and safety of TURP and TVP in patients with symptoms due to obstructive benign prostatic hypertrophy with a prospective multicentric randomized study. MATERIALS AND METHODS: 150 patients with BPH, urodynamically obstructed, were randomized to receive TURP or TVP. At the end of the recruitment phase, 80 patients underwent TURP and 70 patients underwent TVP. Patients were clinically evaluated by the I-PSS score at months 0, 1, 3, 6 and 12. Preoperative evaluation included complete blood routine examination, PSA, transrectal ultrasound and pressure/flow studies. Pressure/flow studies were also performed after 3 months. RESULTS: There was no statistical difference between groups in any of the preoperative parameters. All patients were considered urodynamically obstructed at preoperative pressure studies. As for catheter days and hospitalization days, statistical differences between TVP and TURP were found; catheter days were 2.71 days (SE 0.12) in the TURP group vs. 1.9 (SE 0.24) in the TVP group (p < 0.000). Hospitalization was 4.7 days (SE 0.22) after TURP and 3.9 days (SE 0.24) after TVP (p < 0.000). Mean preoperative I-PSS score was 18.84 and 18.19 in the TVP and TURP groups, respectively. At 3, 6 and 12 months, IPSS was 5.52 and 5.50, 3.77 and 4.94, 3.52 and 4.04 for TURP and TVP, respectively. Mean preoperative peak flow rate (PFR) was 8.78 and 7.26 ml/s for TURP and TVP, respectively; after 3, 6 and 12 months, PFR was 19.21 and 18.8, 20.77 and 20.13, 20.30 and 20.31 ml/s, respectively. After 3 months, 6 patients in the TURP group (7.5%) and 7 patients in the TVP group (10%) were borderline obstructed. 1 patient in the TVP group (1.4%) was still obstructed and underwent TURP. As for complications, 4 patients (5.7%) in the TVP group had stress urinary incontinence after 12 months vs. 1 (1.25%) in the TURP group. DISCUSSION: The present study clearly demonstrates that TVP is as effective as TURP in relieving urinary obstruction due to BPH, it offers some advantages in terms of catheterization and hospital stay, but at the price of a higher incidence of postoperative urine incontinence. Technical improvements might solve this problem in the future, perhaps combining TVP with TURP of the apical tissue.

Mechanism of microwave thermotherapy.

Possible mechanisms by which transurethral microwave thermotherapy creates an improvement in vodiing parameters are reviewed. The therapy creates coagulation necrosis in the hyperplastic adenoma, and thus has the potential to create volume reduction, change in the periurethral tissue, and changes in efferent neuromuscular elements and sensory neural elements. Evidence is presented that suggests that several of these mechanisms are likely important, and there is not a singular mechanism of action.

Laparoscopic tumorectomy for renal cell carcinoma in a HIV-positive patient.

We report on a HIV-positive patient in whom laparoscopic nephron-sparing surgery has been performed. A 47-year-old white male referred for evaluation and treatment of an asymptomatic, serendipitously discovered renal mass. The patient underwent a laparoscopic tumorectomy; indications, surgical technique and rationale are described in detail.

Results of rebiopsy for suspected prostate cancer in symptomatic men with elevated PSA levels.

AIM OF THE STUDY: To develop indications for repeat biopsy in patients with suspected prostate cancer and first negative biopsy. MATERIALS AND METHODS: 148 consecutive patients, submitted to two or more biopsies for suspected prostate cancer, were extracted from our database on prostatic diseases. Patients were stratified according to the results of the last biopsy (benign or carcinoma) considering the results of the first and of the last biopsy when more than two biopsies had been performed. PSA velocity was calculated when the interval between PSA obtained before the initial and the final biopsy was at least 6 months; PSA velocities were annualized and absolute changes between the two groups were analyzed. RESULTS: Prostatic carcinoma was detected in 60 of the 148 patients (40.5%), including 19 of 41 (46.4%) with prostatic intraepithelial neoplasia (PIN) and 45 of 107 (42.1%) with normal tissue or prostatic epithelial atrophia on initial biopsy. 20% of patients (4 of 20) with low-grade PIN and 71.1% (15 of 21) with high-grade PIN had cancer at repeat biopsy. The mean PSA value of patients with carcinoma on the repeat biopsy was higher than that of patients without carcinoma (13.3 vs. 10.7 ng/ml). However, this difference was not statistically significant (p = 0.37). Mean PSA velocity increased for patients with a final diagnosis of carcinoma versus those without evidence of carcinoma (+0.3 vs. +1.4 ng/ml/year); this difference was statistically significant (p = 0.002). CONCLUSIONS: According to these results, patients with either PIN II-III, or high PSA and PIN I on initial biopsy, and/or with elevated PSA velocity (more than 1 ng/ml/year) should undergo repeat prostate needle biopsy, being at high risk of prostate carcinoma.

Clinical stage, prostate-specific antigen and Gleason grade to predict extracapsular disease or nodal metastasis in men with newly diagnosed, previously untreated prostate cancer. A multicenter study. A. Ur. O. Cooperative Group.

OBJECTIVE: To draw nomograms for preoperative predictions of extracapsular and of nodal disease based upon preoperative prostate-specific antigen, Gleason grade and clinical stage. METHODS: The complete charts of 1,738 patients submitted to radical retropubic prostatectomy in 34 Italian urological departments have been reviewed. The correlation between preoperative variables and pathological examination was tested by both univariate and multivariate techniques. Logistic regression analysis with the likelihood ratio chi 2 test was used to predict the pathological features (T > = 3; N+) of a patient for various combinations of preoperative variables. RESULTS: Probability plots were constructed for the prediction of either extracapsular disease or lymph node involvement by the above-mentioned combination of preoperative variables. CONCLUSIONS: The obtained probability curves could be useful for patient counselling, for planning a staging laparoscopic lymphadenectomy in high-risk patients and for deciding whether to perform a nerve-sparing prostatectomy.

Retroperitoneoscopic treatment of ureteropelvic junction obstruction.

PURPOSE: To demonstrate feasibility and safety of retroperitoneoscopic treatment of ureteropelvic junction obstruction. MATERIALS AND METHODS: 11 patients with symptomatic ureteropelvic junction obstruction were selected for retroperitoneoscopic pyeloplasty. Operative time ranged between 2 h 30 min and 4 h (mean 3 h 10 min); in 5 cases we had to convert to open surgery and an open pyeloplasty was performed through a minimal (6 cm) lombotomic incision. RESULTS: Follow-up IVPs were performed in all patients approximately 2-3 weeks after stent removal. In all patients, a reduction in the grade of hydronephrosis was observed. Significant improvement was noticed in 9 patients; in 2 patients a moderate improvement was observed. CONCLUSIONS: Our experience with retroperitoneoscopic treatment of ureteropelvic junction obstruction demonstrates that also with this approach it is possible to perform reconstructive procedures, with minimal complications. Technical refinements will progressively reduce the conversion rate to open surgery, even if done through minilaparotomy.

Videoendoscopic retroperitoneal cutaneous ureterostomy.

Since January 1993, 10 patients with bilateral ureteral obstruction due to advanced pelvic cancers underwent videoendosurgical cutaneous ureterostomy. Five patients had prostate cancer, three had uterine cancer, and only two had bladder cancer. In five cases a bilateral laparoscopic transperitoneal procedure (LCU) was performed. In five cases a retroperitoneal laparoscopic technique (RLCU) was adopted, and only in one out of these five cases was the procedure done bilaterally. All the procedures were done under general anesthesia. The procedure was accomplished in all the cases without any intraoperative complication. Monolateral retroperitoneal laparoscopic cutaneous ureterostomy (RLCU) required 35-42 min, including the dilation time. Bilateral RLCU required extra time for changing the position of the patient. Postoperative pain was rather insignificant and did not require additional medication. Postdiversion hospital stay was 3-6 days depending on the general condition of the patient. The mean follow-up was 14.4 months.

Procollagen type I carboxyterminal extension peptide in serum: a reliable marker of bone metastatic disease in newly diagnosed prostate cancer?

OBJECTIVE: This study evaluates the accuracy of type I procollagen, a bone matrix glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the results of radionuclide bone scan in newly diagnosed, previously untreated patients with prostate cancer. METHODS: 74 patients underwent serum PSA and procollagen determination using specific antibodies. A staging radionuclide bone scan was then performed; patients with positive bone scan were submitted to x-rays of the suspicious zones. Then, we calculated sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of procollagen and PSA in the detection of bone metastases. RESULTS: Procollagen alone had 83.3% sensitivity, 96% specificity, 90.9% positive predictive value, 92.3% negative predictive value and 91.9% overall accuracy. PSA alone had 70.1% sensitivity, 86% specificity, 70.8% positive predictive value, 86% negative predictive value and 81.1% overall accuracy. CONCLUSIONS: According to our data, we no longer perform a staging radionuclide bone scan in patients with PSA < 20 ng/ml and normal procollagen level, diminishing the number of radionuclide bone scans and increasing the overall net savings for the health care system.

Heat-expansible permanent intraurethral stents for benign prostatic hyperplasia and urethral strictures.

We report our experience with the insertion of a new thermoexpansible permanent intraurethral stent, the Memotherm. We treated 49 patients, 25 with benign prostic hyperplasia (BPH), 21 with recurrent urethral strictures (2 cervicourethral and 18 bulbar and 1 of a vescicourethral anastomosis after radical prostatectomy), and 3 with sphincterotomies (2 for dyssynergia and 1 with incontinence plus stenosis). The patients' ages ranged from 24 to 84 (mean 59.7) years. In all patients, stent insertion was achieved without any operative problem. In two patients, stents were removed (one in the BPH group and one in the urethral stricture group), and at long-term follow-up, we have seen two patients with severe mucosal hyperplasia.

Evaluation of cervico-urethral obstruction with ambulatory pressure/flow studies: an alternative to conventional pressure/flow studies?

Most of the urodynamic studies are conducted in the laboratory during a brief recording time and under nonphysiological conditions and, thus, may fail to unfold the nature of existing pathological conditions of the lower urinary tract; false positives and false negatives are possible. To overcome some of the difficulties associated with conventional P/F studies we have developed, with the cooperation of Medical Measurement System company, Entschede, The Netherlands, a portable system (UDS 2000) for ambulatory monitoring of intravesical pressure, abdominal pressure and EMG connectable with a weight-transducer flowmeter that allows to perform Holter P/F measurements. We compared the results obtained with conventional P/F studies and with Holter P/F studies in 58 BPH patients. During the filling phase we observed a slightly increased number of stable detrusors with Holter P/F recording (46 vs 42); conversely, the number of patients suffering from urge incontinence was the same (7 pts). During the voiding phase, out of 45 patients considered obstructed at conventional P/F study, only 42 were really urodynamically obstructed (93.3%), while other 3 patients had bordeline obstruction. 4 patients with bordeline obstruction at conventional P/F study were considered non-obstructed after Holter P/F. In conclusion, Holter P/F proved to be reliable in the assessment of bladder function during storage and emptying in BPH patients and to be more specific in defining outlet obstruction than the conventional study because of the physiologic filling, the reduction of urethral irritation, the lack of a urethral catheter either during filling or voiding, and the reduction of emotional stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Laparoscopically assisted transvaginal radical cystectomy.

Herein we describe 5 cases of anterior pelvic exenteration in females through a combined transvaginal and laparoscopic approach for bladder cancer. In 4 cases hysterectomy and bilateral ovariectomy were performed. As far as urinary diversion is concerned, a bilateral cutaneous ureterostomy was performed in the 1st case, and in the remaining 4 an ileal conduit was accomplished through a minilaparotomy at the stoma site. The surgical specimen was withdrawn 'en bloc' transvaginally in all cases except 1, in whom vaginal atrophy forced us to perform a midline minilaparotomy. Total operative time ranged between 6 and 9 h, and 4 patients were discharged after 7-11 days with no complications. One patient was discharged only after 18 days due to obesity and diabetic problems. A larger series is needed to confirm the advantages of the combined transvaginal and videolaparoscopic approach for anterior pelvic exenteration as compared to the conventional procedure, with special regard given to the oncological outcome. Our initial experience is surely encouraging.

Benefits and complications of laparoscopic pelvic lymphadenectomy for detection of stage D1 prostate cancer: a multicenter experience.

One hundred fifty-eight consecutive patients with clinically localized prostate cancer were submitted to staging laparoscopic pelvic lymphadenectomy (LPL) at 5 cooperative centers with one or more of the following conditions which were considered as risk factors for nodal disease: clinical stage C (or T3) disease, serum prostate-specific antigen > 20 ng/ml, Gleason sum > 6. The mean number of lymph nodes removed was 11 (range 2-29). Metastases from prostate cancer were found in 41 patients (25.9%). The proportion of lymph node-positive patients increases significantly with the presence of one, two or three of the conditions considered as risk factors (p < 0.00005). The benefit of LPL is limited to the lymph node-positive patients who can be spared a second operation.

Videoendoscopic cutaneous ureterostomy for palliative urinary diversion in advanced pelvic cancer.

Since January 1993, 9 patients with bilateral ureteral obstruction due to advanced pelvic cancers underwent videoendosurgical cutaneous ureterostomy. Five patients had prostate cancer, 3 had uterine cancer and only 1 bladder cancer. In 5 cases a bilateral laparoscopic transperitoneal procedure was performed. In 4 cases a retroperitoneal laparoscopic technique was adopted and only in 1 out of these 4 cases the procedure was done bilaterally. All the procedures were done under general anesthesia. The procedure was accomplished in all the cases without any intraoperative complication; the operative time ranged between 35 and 130 min. Postoperative pain was rather insignificant and did not require additional medication. Postdiversion hospital stay ranged from 3 to 11 days according to the general condition of the patients. The mean follow-up is 10.8 months. In conclusion, retroperitoneal laparoscopic cutaneous ureterostomy seems to be a reasonable alternative to percutaneous nephrostomy in case of bilateral ureteral obstruction due to advanced prostate or uterine cancer, provided that the clinical condition of the patient allows general anesthesia.

Laparoscopic bilateral cutaneous ureterostomy for palliation of ureteral obstruction caused by advanced pelvic cancer.

In cases of advanced urologic malignancies with impairment of renal function secondary to tumor infiltration in high-risk patients, the possibility of performing a laparoscopic instead of an open cutaneous ureterostomy should be considered. We performed laparoscopic cutaneous ureterostomy in three male patients, two with prostate cancer and one with bladder cancer, and in one female patient with uterine cancer. Five operative ports were used. The ureters were identified, dissected, severed, and passed through two 10-mm ports; and cutaneous ureterostomies were performed in the usual manner. The mean operative time was 96 minutes. Patients were discharged after 5 to 7 (mean 6) days. The two patients with prostate cancer are now in treatment with GnRH analogues with a follow-up of 3 and 7 months. The patient with bladder cancer underwent palliative radiotherapy and is well after 6 months. The patient with uterine cancer has stable disease after 3 months. Laparoscopic urinary diversion causes less discomfort and has a low complication rate and may be the first-choice diversion in patients with advanced cancer who have a life expectancy longer than 6 months.

Evaluation of cervico-urethral obstruction with ambulatory pressure/flow studies: an alternative to conventional pressure/flow studies?

Most of the urodynamic studies are conducted in the laboratory during a brief recording time and under nonphysiological conditions and, thus, may fail to unfold the nature of existing pathological conditions of the lower urinary tract; false positives and false negatives are possible. To overcome some of the difficulties associated with conventional P/F studies we have developed, with the cooperation of Medical Measurement System company, Entschede, The Netherlands, a portable system (UDS 2000) for ambulatory monitoring of intravesical pressure, abdominal pressure and EMG connectable with a weight transducer flowmeter that permits performing Holter P/F measurements. We compared the results obtained with conventional P/F studies and with the Holter P/F studies in 58 BPH patients. During the filling phase we observed a slightly increased number of stable detrusors with Holter P/F recording (46 vs 42); conversely, the number of patients suffering from urge incontinence was the same (7 pts). During the voiding phase, out of 45 patients considered obstructed at conventional P/F study, only 42 were really urodynamically obstructed (93.3%), while 3 other patients had borderline obstruction. Four patients with borderline obstruction at conventional P/F study were considered nonobstructed after Holter P/F.

Prostate cancer detection in BPH patients.

The first problem to be solved in the evaluation of BPH patients is surely the differential diagnosis with prostate carcinoma. We evaluated the impact of a combined approach for prostate cancer detection using DRE, PSA, TRUS and ultrasound-guided biopsy, determining the sensitivity and specificity of different tools, in order to obtain a diagnostic algorithm to be used for pretreatment differential diagnosis between prostate cancer and BPH.

Laparoscopic pelvic lymphnodes dissection for prostate and bladder cancer: indication, techniques and results.

Laparoscopic pelvic lymphadenectomy has been proposed for staging of prostate cancer and it might be used, in selected cases, also in bladder cancer. On a total of 31 laparoscopic lymphadenectomies (LPND), 18 for prostate cancer and 13 for bladder cancer, we found positive nodes in 8 cases (26.1%), 4 in prostate and 4 in bladder cancer group. We had no intraoperative complications and negligible postoperative complications (in 10% of cases shoulder-tip pain and in 24% subcutaneous emphysema); all these spontaneously disappeared after 24-36 hours. Patients with negative nodes underwent radical surgery except two prostate cancer patients who underwent radiotherapy, and patients with positive nodes underwent hormonal therapy (for prostate cancer) or chemoradiotherapy protocol (for bladder cancer). In conclusion, laparoscopic lymphadenectomy proved to be a feasible and safe method for staging urological malignancies, being less invasive, with shorter hospitalization and postoperative convalescence than open lymphadenectomy. It should be mainly indicated in high risk prostate cancer patients (elevated PSA and/or Gleason score). In bladder cancer patients, it could be proposed in bladder sparing investigational protocols, as the percentage of pelvic nodes metastases in T2/T3 bladder cancer is sufficiently high to justify an additional staging procedure.

Transurethral ultrasound-guided laser-induced prostatectomy. Objective and subjective assessment of its efficacy for treating benign prostatic hyperplasia.

We describe our experience with transurethral ultrasound-guided laser-induced prostatectomy (TULIP), a new procedure to relieve bladder outlet obstruction caused by benign prostatic hyperplasia. This device is composed of a real-time 7.5 MHz ultrasound transducer coupled to a Nd:YAG laser that fires through an intraprostatic balloon. To date, we performed 16 TULIP procedures; all patients were evaluated from a subjective point of view by a questionnaire based on the Boyarsky scale. They all underwent complete urodynamic studies, including flowmetry with measurement of the residual volume (by catheter) and pressure/flow studies. Preoperative symptom score ranged between 7 and 14 (mean 11.4). Preoperative peak flow rates ranged between 0 and 13 ml/s (mean 6.8). Suprapubic drainage was kept for a mean of 11.6 days after the procedure (7-20 days). Postoperative acute retention was observed in 4 patients (25%) 5-7 days after the procedure. In 13 out of 16 patients, urodynamic obstruction was corrected by the procedure. Two patients kept a borderline obstruction. In 1 case transurethral resection of the prostate (TURP) was performed for persisting obstruction and in another case TURP was performed for persisting untreatable irritative symptoms. At 3 months after the operation, the Boyarsky symptom score (11 patients) ranged between 3 and 12 (mean 7.7) and peak flow rates ranged between 11 and 30 ml/s (mean 16.3). One patient is managed with a suprapubic tube. Retrograde ejaculation was observed in 2 out of 9 patients (22.2%). With a mean follow-up of 6.7 months, we did not observe any late complication.