Precision surgery and genitourinary cancers.

The landscape of the surgical management of urologic malignancies has dramatically changed over the past 20 years. On one side, better diagnostic and prognostic tools allowed better patient selection and more reliable surgical planning. On the other hand, the implementation of minimally invasive techniques and technologies, such as robot-assisted laparoscopy surgery and image-guided surgery, allowed minimizing surgical morbidity. Ultimately, these advances have translated into a more tailored approach to the management of urologic cancer patients. Following the paradigm of "precision medicine", contemporary urologic surgery has entered a technology-driven era of "precision surgery", which entails a range of surgical procedures tailored to combine maximal treatment efficacy with minimal impact on patient function and health related quality of life. Aim of this non-systematic review is to provide a critical analysis of the most recent advances in the field of surgical uro-oncology, and to define the current and future role of "precision surgery" in the management of genitourinary cancers.

Post-void residual urine volume is not a good predictor of the need for invasive therapy among patients with benign prostatic hyperplasia.

PURPOSE: We assessed the value of baseline PVR as predictor of the need for invasive therapy during long-term followup of patients with clinical BPH treated initially with alpha1-blockers or WW. MATERIALS AND METHODS: The records of a cohort of 942 patients with BPH treated with alpha(1)-blockers or WW were reviewed. Baseline I-PSS scores, PSA, prostate volume, uroflowmetry, pressure flow parameters and followup data were collected prospectively. Correlations between PVR and other baseline parameters were calculated. The 5-year cumulative risks of invasive therapy were calculated with the Kaplan-Meier method. After stratification of PVR by various cutoff levels (50, 100 and 300 ml), rate ratios between large and small PVRs were calculated using proportional hazards analyses. RESULTS: PVR has weak (-0.2

Recurrent pancreatitis after trimethoprim-sulfamethoxazole rechallenge.

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.

Endocrine approaches in the therapy of prostate carcinoma.

At present, the management of non-organ confined prostate cancer, whether it is a recurrence or metastasis, continues to evolve based on prostate cancer detection using prostate-specific antigen and the development of medications as alternatives for the classical orchiectomy, which induced irreversible implications for quality of life. Diethylstilbestrol therapy was associated with cardiovascular side-effects; GnRH agonists were able to create a castration level, but again considerable side-effects were described. Combination therapies using antiandrogens and GnRH agonists do not improve survival and have additional toxicity. GnRH antagonists, which also suppress FSH, represent the latest class of agents introduced for hormonal treatment, but phase III studies with survival data are not yet available. In spite of all these achievements, hormonal manipulation has resulted in only modest improvements during recent decades and new targets are needed to improve the clinical outcome. Selectively modifying the androgen receptor is currently one of the most promising developments.

Prognostic role of prostate-specific antigen and prostate volume for the risk of invasive therapy in patients with benign prostatic hyperplasia initially managed with alpha1-blockers and watchful waiting.

OBJECTIVES: To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice. METHODS: Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy. RESULTS: Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0. CONCLUSIONS: A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). METHODS: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values. RESULTS: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml. CONCLUSIONS: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.

Transurethral resection vs microwave thermotherapy of the prostate: a cost-consequences analysis.

OBJECTIVE: To compare the costs and outcome of high-energy transurethral microwave thermotherapy of the prostate (HE-TUMT) with transurethral resection of the prostate (TURP), as the former is considered to be the best minimally invasive method for managing lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Between January 1996 and March 1997, 144 patients were randomized to treatment with HE-TUMT (78) using the Prostatron device and Prostasoft 2.5 software (EDAP Technomed, Lyon, France), or TURP (66). At baseline and during the annual follow-up, patients were evaluated by the International Prostate Symptom Score and uroflowmetry (maximum flow rate and postvoid residual volume). Kaplan-Meier survival analyses were used to calculate the cumulative risk of re-treatment. A cost-consequences analysis was performed based on the prospective measurement of healthcare use, with costs expressed as Netherland guilders (NLG). RESULTS: During a 3-year follow-up period, the mean (95% confidence interval) risk of re-treatment was 22.9 (12.5-33.2)% and 13.2 (4.5-21.9)% for HE-TUMT and TURP, respectively (P = 0.215). The mean direct cost of treatment was 3450 (3444-3456) and 6560 (5992-7128) NLG for HE-TUMT and TURP, respectively. The mean total (including re-treatments), discounted (4%) 3-year cost for the HE-TUMT and TURP group was 5300 (4692-5908) and 7800 (7118-8482) NLG, respectively. CONCLUSIONS: In this prospective randomized trial, HE-TUMT and TURP had a comparable 3-year risk of re-treatment. Healthcare expenditure on HE-TUMT, mainly because it is an outpatient treatment, was significantly lower than for TURP.

A randomized study comparing epirubicin in a 4-weekly versus a weekly intravenous regimen in patients with metastatic, hormone resistant, prostatic carcinoma: effects on health related quality of life.

The treatment of hormone resistant prostate cancer) with epirubicin 25 mg/m(2)(Epi25) on a weekly intravenous regimen may be better in terms of health related quality of life (HRQOL) than with 100 mg/m(2)(Epi100) on a 4-weekly regimen. A total of 79 patients who filled out the EORTC-QLQ-C30 questionnaire for the assessment of HRQOL could be evaluated. Compared with the baseline, no changes in HRQOL function scales or significant changes in the following HRQOL symptom scales were found. The Epi25 group reported less pain during the first 3 months and the Epi100 group more dyspnoea after 4 weeks and less pain and less insomnia but more loss of appetite after 8 weeks. In both groups, toxicity was comparable, except for World Health Organisation grade II-III alopecia occurring in 82% in the Epi100 versus 31% in the Epi25 group. There were no significant differences between groups in response rates and survival. In this study, HRQOL was not improved which is in line with other studies using only epirubicine. Epirubicin as single agent therapy should not be used in future treatment of patients with HRPC.

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Microvessel density: correlation between contrast ultrasonography and histology of prostate cancer.

OBJECTIVE: Increased microvessel density (MVD) of prostate cancer seems to be associated with poor prognosis and higher stage. Assessment of MVD using noninvasive methods could be of use in the work-up of patients with prostate cancer. The aim of the present study was to correlate three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) findings with MVD characteristics of radical prostatectomy specimens. METHODS: Seven patients with biopsy-proven prostate cancer had 3D-CE-PDU investigations 2-3 weeks after prostate biopsies were taken and prior to radical prostatectomy. The investigations were performed using Levovist contrast agent (Schering AG, Berlin, Germany) in combination with a Voluson 530D ultrasound scanner (Kretz AG, Zipf, Austria). The 7 patients were selected because of lateralization of the contrast enhancement. Histology slides were made of the side with 'contrast enhancement' and of the contralateral 'unenhanced' side and stained according to the catalyzed reporter deposition (CARD) amplification procedure, and MVD parameters were obtained. RESULTS: In all patients the MVD count of the 'enhanced' side was higher than the MVD count of the 'unenhanced' side, averaging 1.93 times higher. On histology all enhanced lesions proved to contain prostate cancer tissue (average maximum diameter 25 mm (range 17-31)). Two patients had a small bilateral tumor lesion (4 and 5 mm respectively) and in total 5 patients had even smaller satellite lesions (1-2 mm). The smaller lesions were not identified using 3D-CE-PDU. CONCLUSIONS: The present study shows that 3D power Doppler contrast ultrasonography is a minimally invasive imaging modality, which has the potential to visualize lesions with increased MVD. This property of 3D-CE-PDU could be used in the detection of prostate cancer.

Can biological markers replace cystoscopy? An update.

Cystoscopy is currently considered the gold standard for the detection of bladder tumors. The role of urine cytology in the initial detection and follow-up of patients is under discussion. New elaborative and rapid assays are available that may circumvent the low sensitivity and poor reproducibility of urine cytology. The methods that have been tested extensively are the nuclear matrix protein (NMP22) assay, the BTA stat assay, and the BTA TRAK enzyme-linked immunosorbent assay. Both outperform cytology in the detection of low-grade lesions. The specificity of both assays, however, lags behind that of cytology. The data from retrospective analyses are insufficient to justify clinical integration, and the need to replace cystoscopy with these novel assays remains to be proven.

Posterior tibial nerve stimulation as neuromodulative treatment of lower urinary tract dysfunction.

PURPOSE: Recently, intermittent percutaneous posterior tibial nerve stimulation was introduced as a treatment modality filling the gap between conservative and surgical therapies in patients with certain types of lower urinary tract dysfunction. MATERIALS AND METHODS: In a prospective multicenter trial posterior tibial nerve stimulation was evaluated in 37 patients who presented with symptoms of bladder overactivity, that is the urgency and frequency syndrome and/or urge incontinence, and 12 with nonobstructive urinary retention. Results were recorded in voiding diaries and on quality of life questionnaires before and after treatment. Patients were classified as responders, including those in whom therapy was successful and chose to continue treatment after the initial 12 weeks, and nonresponders, those who chose to stop treatment. RESULTS: Overall, a positive response was seen in 60% of all patients. In patients with bladder overactivity a statistically significant decrease was observed in leakage episodes, number of pads used, voiding frequency and nocturia, and an equal increase in mean and smallest volume voided. Improvements were also seen in nonobstructive urinary retention, including number of catheterizations, total and mean volume catheterized, and total and mean volume voided. Disease specific quality of life and some domains of general quality of life improved, especially of bladder overactivity. Only mild side effects were observed. CONCLUSIONS: Posterior tibial nerve stimulation is a minimally invasive and successful treatment option for patients with certain types of lower urinary tract dysfunction.

Long-term followup of randomized transurethral microwave thermotherapy versus transurethral prostatic resection study.

PURPOSE: We evaluate the durable effect of high-energy transurethral microwave thermotherapy and transurethral prostatic resection for treatment of patients with lower urinary tract symptoms suggestive of bladder outflow obstruction. MATERIALS AND METHODS: Between January 1996 and March 1997, 155 patients with lower urinary tract symptoms suggestive of bladder outflow obstruction were randomized to receive transurethral microwave thermotherapy (Prostatron*; device and commercial software) (82) or undergo transurethral prostatic resection (73). Initial patient evaluation was performed according to international standards. Patients were followed annually with the International Prostate Symptom Score (I-PSS) and uroflowmetry (maximum flow rate). The Kaplan-Meier survival analysis was used to calculate the cumulative risk of re-treatment, adjusted for loss to followup. RESULTS: A total of 78 patients received transurethral microwave thermotherapy and 66 underwent transurethral prostatic resection. Median followup was 33 months. In the thermotherapy group mean maximum urinary flow rate improved from 9.2 ml. per second at baseline to 15.1, 14.5 and 11.9 ml. per second at 1, 2 and 3 years, and mean I-PSS decreased from 20 to 8, 9, and 12, respectively. In the resection group the corresponding numbers for maximum urinary flow rate were 7.8, 24.5, 23.0 and 24.7 ml. per second at 1, 2 and 3 years, and for I-PSS were 20, 3, 4 and 3, respectively. At 36 months, 14 patients in the thermotherapy and 8 from the resection groups underwent re-treatment, and the cumulative risk was 19.8% (95% confidence interval 10.4% to 29.3%) and 12.9% (4.5% to 21.3%), respectively (p = 0.28). CONCLUSIONS: Transurethral microwave thermotherapy and transurethral prostatic resection achieve durable improvement in patients with lower urinary tract symptoms suggestive of bladder outflow obstruction, while the magnitude of improvement is higher with resection. The repeat thermotherapy is based on failure of therapy whereas repeat resection is based on complications of therapy.

Branching activity in the human prostate: a closer look at the structure of small glandular buds.

OBJECTIVE: Knowledge regarding cell biologic characteristics of small solid glandular buds in the prostate and their relationship with branching activity in the human prostate is still fragmentary. Our object was to demonstrate, on the basis of immunophenotype, loci that harbor the potential for branching activity within the adult human prostate. MATERIALS AND METHODS: Semiserial sectioning was performed on 13 adult prostates in an effort to identify structures in the prostate that could be considered foci of growth. Selected slides were stained with biomarkers for basal/luminal cells (keratins), proliferation (MIB-1), apoptosis inhibitor (bcl-2), intercellular adhesion (E-cadherin), and stromal-epithelial interactions (tenascin-C). Results were compared with fetal and prepubertal human prostates and microdissected rat prostates. RESULTS: Five histologic epithelial structures were identified in 19 paraffin blocks, which on serial sectioning showed morphologic transitions with a common pattern, consisting of reduction in number and caliber of acini until small solid buds of epithelial cells were reached. Immunophenotypically, the small solid glandular buds had a basal-cell keratin phenotype, expression of bcl-2 in virtually all cells, high proliferative activity, prominent intracellular localization of E-cadherin, and enhanced periglandular tenascin-C immunoreactivity. The budding tips in fetal and prepubertal prostates revealed an immunostaining pattern identical to the small solid glandular buds in the adult, but different to the rat prostate. CONCLUSIONS: Our data suggest that dispersed small solid glandular buds have a capacity for growth, and as such may be considered foci of resumed reawakening branching activity with in the adult human prostate.

Intra-prostatic vasculature studies: can they predict the outcome of transurethral microwave thermotherapy for the management of bladder outflow obstruction?

BACKGROUND: Blood perfusion regulates intraprostatic temperatures during transurethral microwave thermotherapy (TUMT). We evaluated baseline intraprostatic vasculature, as a predictor of efficacy of TUMT. METHODS: Twenty-two patients, with lower urinary tract symptoms (LUTS) suggestive of bladder outflow obstruction, were treated with TUMT (Prostatron). At baseline, three-dimensional contrast-enhanced power-flow-Doppler prostate ultrasonography (3D-CE-PFD) was performed. Assuming that the percentage of perfused area (PPA) is a realistic measure of blood flow, it was used to quantify intraprostatic vasculature. RESULTS: The median (range) age, prostate size, and energy delivered were 66 years (48-80), 47 cm(3) (30-121), 110 kJ (29-136), respectively. The response was 77% (5 failures). The median (range) PPA was 2.76% (0.7-11.3). No difference in PPA among good and poor responders was detected nor was any correlation between PPA and baseline parameters. CONCLUSIONS: The baseline intraprostatic vascularization, documented by CE-PFD studies, has no predictive value for the efficacy of TUMT. It seems that "static" baseline blood flow does not reflect the "dynamic" thermoregulatory role of blood flow during treatment.

Correlation of transrectal ultrasound, computer analysis of transrectal ultrasound and histopathology of radical prostatectomy specimen.

A system for computerised analysis of ultrasonographic prostate images (AUDEX=Automated Urologic Diagnostic EXpert system) for the detection of prostate carcinoma was developed. The ultimate goal is to develop a system that is reliable and non-observer dependent. Results of an earlier study with a small group were encouraging and this study describes the results of the computerised analysis in a larger group. Sixty-two patients who were scheduled to undergo a radical prostatectomy were prospectively analysed. The radical prostatectomy specimens were step-sectioned in the transverse plane, corresponding to the ultrasound pictures. Malignant regions identified by each study were quantified and compared by computer calculation. No correlation was observed between ultrasound analysis and pathology result. For the AUDEX analysis an overall sensitivity of 85% and a specificity of 18% with only a diagnostic accuracy of 57% was noticed when presence or absence of malignancy was evaluated by octant (total 496). When applying a cut-off value of 0.5 ml the numbers were 71%, 33% and 55%, respectively. Correlation was significantly better for the ventral octants. In this study the earlier results of our AUDEX system could not be confirmed. Although sensitivity was good, specificity and especially diagnostic accuracy were lower than expected. We have to conclude that the current settings are inappropriate for routine clinical use. Prostate Cancer and Prostatic Diseases (2001) 4, 56-62

Transurethral microwave thermotherapy in the armamentarium of therapeutic modalities for benign prostatic hyperplasia.

Transurethral microwave thermotherapy (TUMT) has gained a firm place in the spectrum of therapeutic modalities for management of patients with lower urinary tract symptoms suggestive of bladder outflow obstruction. To achieve optimum results following TUMT, intense research focuses on appropriate patient selection, heat-tissue interactions, and modification of technical specifications. Results of TUMT are good to excellent for the majority of patients, but there is a non-negligible number of patients who respond poorly. The selection of favorable candidates for TUMT aims to improve the therapeutic results, and both clinical baseline parameters and intrinsic characteristics of the prostate (histologic composition and vasculature) may influence treatment outcome. TUMT achieves therapeutic response through coagulative necrosis of the hyperplastic tissue, but additional theories have been proposed recently, suggesting that TUMT may cause neural destruction and induce apoptosis. Individualization of the treatment is expected to offer the best results, and because the temperature achieved inside the prostate determines the actual parenchymal necrosis, thermal monitoring during treatment will permit application of microwave energy in a feedback mode. Various microwave devices differ in technical specifications (operating frequency, design of antenna, cooling system), and recently introduced software programs (high-energy protocols, heat-shock strategy, short-duration protocols) aim at better efficacy, providing a more patient-friendly procedure. TUMT has survived the "test of time" that other, initially promising, modalities have failed. What remains to be determined is the maximum benefit that patients and health systems can gain from such a technique.

Efficacy and safety of the new high-energy 30-minute transurethral microwave thermotherapy: results of 1-year follow-up in a multicenter study.

PURPOSE: To assess the efficacy and durability of a new 30-minute algorithm for high-energy transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of men with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 167 men (mean age 67 years) with bothersome LUTS were treated with the new TUMT protocol. Evaluation included assessment of the short- and long-term objective and subjective outcome measures of this treatment. RESULTS: The treatment is well tolerated. The International Prostate Symptom Score improved from a mean of 19.2 at baseline to 7.9 at 12 months after treatment. Maximum urinary flow improved from 8.9 to 16.4 mL/s at 12 months. Mean duration of catheterization was 16.1 days. Urodynamic evaluation showed a change from the obstructed to the nonminimally obstructed zone. There were no serious complications. CONCLUSION: High-energy TUMT using the new high-dose Prostasoft 3.5 protocol appears to be a safe, effective, and durable treatment. The faster procedure improves tolerance of the treatment. Subjective and objective improvements were significant and the treatment-related morbidity low.