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Summary The idea that neoplasms grow, becoming unresectable through dissemination, which is initially loco-regional, and systemic only in a later stage, is historically at the basis of the radical surgery – where, by ‘radical’, the old surgery meant the complete removal of the tumor and, in practice, aggressive surgery. Halsted’s “radical mastectomy”, as well as many principles of surgical anatomy of the first decades of the twentieth century, obey to an idea of tumor progression as a linear process taking place in continuity and contiguity, where the various anatomical layers and the peritumoral desmoplastic reaction are mistaken for a wall of defense against the neoplasm’s dissemination, capable of containing and orienting it. However, the investigations of the processes of invasion and metastasis by Rudolf Virchow and Stephel Paget helped to reorient surgical approaches.

BACKGROUND This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study. METHODS Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), radiotherapy plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain. RESULTS Overall, 1 537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, p

Objective: Overview of bladder cancer (BC) management in Italy during the first month of the COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to analyze performance of different Italian Centers in North, Center and South, with a special eye for Lombardy (the Italian epicenter). Patients and methods: During April 2020, a survey containing 14 multiple-choice questions focused on general staffing and surgical activity related to BC during the months of March 2019 and March 2020 was sent to 32 Italian Centers. Statistical analysis was performed using IBM SPSS Statistics (v26) software. A Medline search was performed, in order to attempt a comparative analysis with published papers. Results: 28 Centers answered, for a response rate of 87.5%. Most of the urology staff in the Lombardy region were employed in COVID wards (p = 0.003), with a statistically significant reduction in the number of radical cystectomies (RC) performed during that time (p = 0.036). The total amount of RC across Italy remained the same between 2019 and 2020, however there was an increase in the number of surgeries performed in the Southern region. This was most likely due to travel restrictions limiting travel the North. The number of Trans-Urethral Resection of Bladder Tumors (TURBT) (p = 0.046) was higher in Academic Centers (AC) in 2020 (p = 0.037).Conclusions: The data of our survey, although limited, represents a snap shot of the management of BC during the first month of the COVD-19 pandemic, which posed a major challenge for cancer centers seeking to provide care during an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Objectives: Real-life overview of bladder cancer (BC) surgical management in Italy during the first month of COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to confront performance of Academic Centers (AC) vs Non Academic Centers (NAC) as well as non-COVID Centers (nCC) and COVID Centers (CC). Patients and methods: During April 2020, an e-mail survey was sent to 32 Sections of Urology across Italy. It contained 14 multiple-choice questions focused on activities during March 2019 and March 2020. Statistical analysis was performed using IBM SPSS Statistics (v26) software. Results28 centers answered to survey. AC and NAC showed statistically significant differences (chi-square test pConclusionThe COVID-19 pandemic represents an important challenge for cancer centers, in the context of an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC.

In the past two decades, the treatment landscape for patients with metastatic renal cell carcinoma has significantly changed thanks to the approval of several targeted molecular therapies (VEGF and mTOR inhibitors) and recently immune-checkpoint inhibitors. The Italian Association of Medical Oncology (AIOM) Renal Cell Cancer (RCC) Guidelines Panel has developed clinical guidelines to provide evidence-based information and recommendations to oncologists, urologists and all professionals involved in the management of patients with renal cell cancer.

Background: The availability of a number of agents that are efficacious in patients with metastatic prostate cancer (mPC) has led to them being used sequentially, and this has prolonged patient survival. However, in order to maximize their efficacy, clinicians need to be able to obtain a reliable picture of disease evolution by means of monitoring procedures. Methods: As the intensive monitoring protocols used in pivotal trials cannot be adopted in everyday clinical practice and there is no agreement among the available guidelines, a multidisciplinary panel of Italian experts met to develop recommendations for monitoring mPC patients using a modified Delphi method. Results: The consensus project considered methods of clinically, radiographically, and biochemically monitoring patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer undergoing chemotherapy and/or hormonal treatment. The panelists also considered the methods and timing of monitoring castration levels, bone health, and the metabolic syndrome during androgen deprivation therapy. Conclusions: The recommendations, which were drawn up by experts following a formal and validated consensus procedure, will help clinicians face the everyday challenges of monitoring metastatic prostate cancer patients.

Different therapeutic options for the management of prostate cancer (PC) have been developed, and some are successful in providing crucial improvement in both survival and quality of life, especially in patients with metastatic castration-resistant PC. In this scenario, diverse combinations of radiopharmaceuticals (for targeting bone, cancer cells and receptors) and nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET and PET/CT) are now available for imaging bone metastases. Some radiopharmaceuticals are approved, currently available and used in the routine clinical setting, while others are not registered and are still under evaluation, and should therefore be considered experimental. On the other hand, radiologists have other tools, in addition to CT, that can better visualize bone localization and medullary involvement, such as multimodal MRI. In this review, the authors provide an overview of current management of advanced PC and discuss the choice of diagnostic modality for the detection of metastatic skeletal lesions in different phases of the disease. In addition to detection of bone metastases, the evaluation of response to therapy is another critical issue, since it remains one of the most important open questions that a multidisciplinary team faces when optimizing the management of PC. The authors emphasize the role of nuclear modalities that can presently be used in clinical practice, and also look at future perspectives based on relevant clinical data with novel radiopharmaceuticals.

Aim: To describe the journey of patients with metastatic castration-resistant prostate cancer (mCRPC) in treatment with radium-223. Methods: A multiperspective analysis was performed using narrative medicine in four Italian centers. Results: The substantial impact of mCRPC on quality of life through all phases of the disease was described. After an initial lack of awareness of the disease or denial of its effects, symptoms of pain, fatigue and side effects often led to sadness, fear and loneliness. The majority underwent radium-223 therapy positively, restoring their quality of life and routine activities. Conclusion: Using narrative medicine, the importance of a patient-centered approach in the pathway of care for patients with mCRPC through all the stages of the disease was highlighted.

Background Decision making in T1 high-grade bladder cancer patients remains a challenging issue in urologic practice. Objective To assess the feasibility and potential prognostic role of three different substaging systems in specimens from both primary and second transurethral resection (TUR) of the bladder in T1 high-grade bladder cancer patients. Design, setting, and participants A total of 250 consecutive, confirmed pure transitional T1 high-grade bladder tumors submitted to second TUR entered the retrospective study. Outcome measurements and statistical analysis Feasibility of two already clinically tested microstaging systems (anatomy-based T1a/T1b/T1c and micrometric T1m/T1e with 0.5-mm thresholds of invasion) and that of a micrometric substage designed by the authors and based on a 1-mm threshold of invasion (Rete Oncologica Lombarda [ROL] system) was assessed by five independent uropathologists on both first and second TUR specimens. Univariable Cox proportional hazards models were attempted to identify significant independent predictors of recurrence and progression after TUR. Kaplan-Meier curves were plotted to compare different substaging methods analyzing recurrence and progression. Results and limitations The ROL system proved to be feasible in nearly all cases at both first and second TUR. Median follow-up was 60 mo. The univariate Cox regression analysis documented the ROL substage (ROL2 vs ROL1) to be the only statistically significant predictor of progression (hazard ratio: 2.01; 95% CI, 1.03–3.79; p Conclusions T1 microstaging using different procedures is feasible on both primary- and second-TUR specimens. A high rate of feasibility may be expected for T1m/T1e and ROL systems. The clinical role of microstaging on second TUR remains to be defined. Patient summary The Rete Oncologica Lombarda system showed feasible results in T1 high-grade bladder tumors. Our substratification was predictive of progression of disease.

We read with interest the paper by M. Lawless et al. very recently published in Histopathology (Stalk versus base invasion in pT1 papillary cancers of the bladder: improved substaging system predicting the risk of progression) (1). The Authors divided tumors into base-focal and base-extensive cases, relying on the criterion of whether or not there was a single focus

Prostate cancer (PC) shows a large prognostic spectrum, which ranges from the indolent to the lethal form and can be cured by two extreme therapies: “doing nothing” (“active surveillance”) or “destroying the prostate” (“radical surgical or radiotherapeutic treatment”). The gulf between these two extremes has been covered by the concept of focal therapy (FT), which is aimed at treating only the affected part of the prostate.

OBJECTIVE To provide evidence-based recommendations on bladder cancer management METHODS A multidisciplinary guideline panel composed of urologists, medical oncologists, radiotherapists, general practitioners, radiologists, epidemiologists and methodologists conducted a structured review of previous reports, searching the Medline database from 1 January 2004 to 31 December 2008. The milestone papers published before January 2004 were accepted for analysis. The level of evidence and the grade of the recommendations were established using the GRADE system. RESULTS In all, 15 806 references were identified, 1940 retrieved, 1712 eliminated (specifying the reason for their elimination) and 971 included in the analysis, as well as 241 milestone reports. A consensus conference held to discuss the discrepancies between the scientific evidence and the clinical practice was then attended by 122 delegates of various specialities. CONCLUSION Recommendations on bladder cancer management are provided.

Despite the high prevalence and huge socio-economic impact of benign prostatic hyperplasia (BPH) in Italy, no national guidelines have been produced so far. This is a summary of the first Italian guidelines on the diagnosis and treatment of lower urinary tract symptoms (LUTS) related to uncomplicated BPH, prepared by a multidisciplinary panel under the auspices of the Italian Association of Urologists and introduced in Italy in 2003. An update compiled by the authors is also included.Relevant papers published from 1998 to 2003 (updated to 2006) were identified through a structured literature review and the quality of evidence presented therein was graded according to the Centre for the Evaluation of Effectiveness in Health Administration (CeVEAS) system. Recommendations were based on evidence from the literature, but also on feedback from practitioners and specialists. MAIN FINDINGS/RECOMMENDATIONS: Given the prevalence of BPH, all men agedor = 50 years of age should be asked about LUTS and informed about disease characteristics and therapeutic options, while sexual function should always be assessed in patients with severe and long-standing LUTS. Initial assessment should include medical history (including drug and co-morbidity history), digital rectal examination, urinalysis, International Prostate Symptom Score-Quality of Life (IPSS-QoL) and a voiding diary, while prostate-specific antigen (PSA) and measurement of prostate volume by suprapubic ultrasonography are indicated in fully informed patients with a life expectancy ofor = 10 years in whom BPH progression could influence treatment choices. QoL considerations should dictate whether to start active treatment. When QoL is not affected by LUTS, watchful waiting is indicated if symptoms are mild, acceptable if they are moderate. When QoL is affected, medical therapy with alpha1-blockers or 5alpha-reductase inhibitors (the latter indicated in patients with increased prostate volume) is appropriate. Combined therapy with alpha1-blockers + 5alpha-reductase inhibitors should only be considered in patients at high risk for progression (prostate volume40 mL or PSA4 ng/mL), since the incremental cost of combination therapy vs. monotherapy with alpha1-blockers or finasteride is prohibitive. Selection of the type of surgery should be based on the surgeon's experience, the presence of co-morbid conditions and the size of the prostate. Open prostatectomy and transurethral resection of the prostate (TURP) are recommended in patients with acute or chronic retention of urine, and acceptable in obstructed patients with moderate/severe symptoms and worsened QoL. Transurethral incision of the prostate (TUIP) is acceptable when prostate volume isor = 30 mL. Holmium laser enucleation of the prostate (HoLEP) may be proposed to motivated patients where expert surgeons are available. Transurethral microwave thermotherapy (TUMT) or transurethral needle ablation (TUNA) may be proposed to motivated patients who prefer to avoid surgery and/or do not respond to medical treatment. The possible effects of medical or surgical treatments on sexual function should always be discussed.These guidelines are intended to provide a framework for health professionals involved in BPH management in order to facilitate decision-making in all areas and at all levels of healthcare.

The RAND appropriateness method was used to explore the relevance of risk factors for disease progression in the treatment choice for patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). A total of, 12 international experts assessed the appropriateness of various treatments for 243 risk profiles. Highest appropriateness rates were found for alpha1-adrenoceptor antagonists (68% of profiles) and combination therapy (46%). A large prostate volume was the dominant argument in favour of 5alpha-reductase inhibitors and combination therapy, but was irrelevant for the choice of surgery. Considerable postvoid residual, severe symptoms and poor maximum flow rate were the most important factors in favour of surgery.

Objective:A randomized multicenter (14 centers) trial was conducted in 114 men with prostate cancer to determine whether the antiestrogen tamoxifen (‘Nolvadex’) 20 mg or the aromatase inhibitor anastrozole (‘Arimidex’) 1 mg prevent gynecomastia and breast pain during treatment with the non-steroidal antiandrogen bicalutamide (‘Casodex’) 150 mg, without compromising efficacy, safety, or quality of life. Plasma samples were collected in a subgroup of these patients to investigate whether trough (pre-dose) concentrations of bicalutamide 150 mg are influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg; the results of this pilot study are reported in this article. Methods: A subpopulation of patients from a randomized placebo-controlled trial evaluating tamoxifen 20 mg and anastrozole 1 mg for the prevention of gynecomastia and breast pain in men receiving bicalutamide 150 mg for early or recurrent prostate cancer were selected on a voluntary basis from three of the trial centers. Plasma samples were collected on days 7, 14, 28, and 84 of therapy and analyzed to determine the plasma concentrations of (R)–bicalutamide and (S)-bicalutamide. In addition, plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were determined. Results: A total of 21 patients were selected. There was no significant difference between treatment groups with respect to the trough plasma concentrations of either bicalutamide enantiomer at any point during the study. Plasma concentrations of the enantiomers, and the relative proportion of the ®)- and (S)–enantiomers, were consistent with those reported in previous studies. Plasma concentrations of tamoxifen, N–desmethyltamoxifen, and anastrozole were also similar to those described elsewhere in the literature. Conclusions: The findings of this pilot study suggest that trough plasma concentrations of bicalutamide enantiomers following administration of bicalutamide 150 mg are not markedly influenced by concomitant administration of tamoxifen 20 mg or anastrozole 1 mg. However, an effect of tamoxifen on bicalutamide pharmacokinetics can not be completely excluded due to the size of this study. Further studies are needed to clarify the effect of tamoxifen on bicalutamide pharmacokinetics and prostate cancer control in bicalutamide-treated patients. ‘Arimidex’, ‘Casodex’, and ‘Nolvadex’ are trademarks of the AstraZeneca group of companies

Background: Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration. Objective: To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated. Design, setting, and participants: This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n = 41) and weekly (n = 39). Median follow-up was 24.2 mo. Intervention: Daily bicalutamide (150 mg) plus daily tamoxifen 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in theweekly group and one in the daily groupwere discontinued for adverse events. Measurements: For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires. Results and limitations: Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group ( p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen ( p = 0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively ( p = 0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far. Conclusions: This study demonstrated that tamoxifen 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.

Objectives Non-muscle invasive bladder cancer (NMIBC) classified as T1G3 represents one of the most challenging issues in urologic oncology. Although it is still considered a lesion amenable for conservative management, the risk for recurrence and progression remains high. The aim of this study was to define both recurrence and progression rate in patients with T1G3 UCC treated by complete transurethral resection (TURT) and adjuvant thermochemotherapy approach. Materials and methods We retrospectively evaluated the clinical data of patients with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT) treatment. Data recorded included age, gender, previous resections, previous intravesical treatment, time to tumor recurrence, and progression. TCT was given once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6 weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was instilled into the bladder in combination with bladder wall hyperthermia of 42 ± 2°C for 60 minutes. Follow-up cystoscopy and urinary cytology were performed every 3 months for the first 2 years and than biannually. Results A total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic centers. Mean age was 68 years (range 35–91), 10 were females and 46 were males. Twenty-six patients failed on at least 1 previous intravesical treatment. Five patients who dropped out due to adverse events before reaching the first outcome evaluation cystoscopy were referred to another intravesical therapy, and were therefore excluded from the current analysis. A total 51 patients were available for analysis. Median follow-up time of tumor-free patients was 18 months (average 20, range 2–49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of them progressed to muscle invasive disease. The median time to recurrence was 9 months (average 11, range 2–31 months). The Kaplan-Meier estimated recurrence rate for this group is: 42.9% at 2 years, 51.0% at 4 years. Conclusions TCT can be an effective adjuvant treatment option after TURT to prevent recurrence in patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%). TCT treatment was documented to be effective also in those who failed previous intravesical BCG. Treatment was confirmed to be safe and well tolerated.

Background: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted us to investigate the activity of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate cancer. Methods: Eighty-two patients were randomly assigned to receive prednisone plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On progression, patients initially assigned to placebo were offered the possibility to receive gefitinib. Best prostate-specific antigen response was the primary endpoint. Results: At a median follow-up time of 29.0 months (26.0–32.0), 77 patients progressed and 51 died. Prostate-specific antigen response was recorded in 6/38 (15.8%; 95% CI 4.2–27.4) and in 5/44 (11.4%; 95% CI 2.0–20.8) patients in pG and ppl groups, respectively. There was no difference between groups in time to progression (median pG 4.0 months, range 3.5–4.5; median ppl 4.5 months, range 3.5–5.0) and survival (median pG 26.5 months, range 16.0–37.0; median ppl 20.5 months, range 14.0–27.0). Adverse events occurred in 19 patients in each arm and were generally mild. Conclusions: pG showed a good tolerability profile but only a limited therapeutic activity in hormone-refractory prostate cancer.

Objective: Incidence of venous thromboembolism (VTE) and need for thromboprophylaxis in urologic surgery have received little attention since only one randomised study has addressed this issue in the last 20 yr. The present prospective observational study evaluated incidence and risk factors for clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and compared findings in urologic patients with those in patients undergoing general or gynaecologic surgery. Methods: Patients having cancer surgery (general surgery, gynaecology, urology) were assessed for clinically overt VTE occurring up to 30 +/- 5 d after intervention or more if the hospital stay was longer. All suspected WE events were evaluated by an external independent Adjudication Committee. Results: A total of 2373 patients, 1238 (52%) undergoing general surgery, 685 (29%) urologic, and 450 (19%) gynaecologic surgery were evaluated. In urologic patients, most procedures (61%) were endoscopic, with bladder and prostate cancer being the most frequent tumours. In-hospital thromboprophylaxis was given to 71.7% of patients, whereas 32.5% received prophylaxis after discharge. The incidence of VTE in urologic patients was lower (0.87%) than that in general surgery and gynaecologic patients (2.8% and 2.0%, respectively). WE consisted of three cases of nonfatal and three cases of fatal pulmonary embolism (PE). In four of the six cases, WE occurred during prophylaxis. Conclusions: VTE still represents a severe complication and remains the most common cause of death after urologic cancer surgery. Efforts should be made to optimise prophylactic measures to further reduce such risk. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression. Patients and methods IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia. Results Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (pConclusions The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.

Purpose To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. Patients and Methods A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. Results Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by ≥ 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone–binding globulin levels. Conclusion Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P = .08 and P = .04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P = .01) and of erectile dysfunction (P = .002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

e16080 Background: BM is a valuable option for pca pts who wish to avoid the consequences of androgen deprivation and to mantain sexually active.BM is commonly well tolerated:however gy and mastalgia virtually develop in all pts and represent a major cause of treatment discontinuation. We had previously demonstrated that T is safe and effective in preventing breast events induced by BM without affecting B tumor activity (Boccardo, J Clin Oncol. 2005;23:808). However possible interferences between B and T,especially after prolonged administration, remain a matter of concern.In order to reduce the exposure to T,we considered the putative advantages of a weekly administration based on T effects being dose -dependent and on drug long half-life. Methods: This was a non inferiority trial. 80 pts with localized, locally advanced or biochemically recurrent pca were randomly assigned to receive daily B (150 mg) plus T 20 (mg) continuously (d group: n = 41) or same but with T at 20 mg/weekly after the first 8 weeks (wk group: n = 39). Gy (primary endpoint), breast pain (bp), serum PSA levels and sexual functioning scores were evaluated. Results: At a median F.U. of 24.2 mos (95% CI: 23.7 -24.6) gy developed in 31.7% of pts in d group and in 74.4% of pts in wk group (p < 0.000). Bp occurred in 12.2% and 46.1% of pts respectively (p = 0.008) and it was more severe in patients switched to weekly T. The incidence of Aes was comparable (d group:58.8%;wk goup: 56.4%). However most events were mild and easily manageable. There were no major differences among treat. schedules relative to sexual functioning scores, PSA behaviour and disease progression. Conclusions: This study failed to demonstrate that it might be possible to maintain comparable prophylactic effect of T by switching from a daily to a weekly schedule and confirms that T at the daily dose of 20mg is safe and effective in preventing the incidence and severity of BM induced breast events. No significant financial relationships to disclose.

5070 Background: In spite of EGF-R overexpression in 40%-80% of pts with HRPC, the results achieved so far with G, a selective EGF-R tyrosine kinase inhibitor have been dismal. This trial was designed to investigate the activity of G when combined with P, a common therapeutic option for HRPC pts. Methods: HRPC pts unresponsive to antiandrogen withdrawal were given P (10 mg/d) plus G (250 mg/d) or pl. On progression, pts initially assigned to pl were offered the possibility to receive G. This was a one-stage trial, and 37 pts per arm were required. Best PSA response (any decrease = 50% in baseline PSA confirmed 4 wks apart) was the primary end-point. Time to disease progression, OS and toxicity were secondary end-points. Results: 82 pts were enrolled (GP: 38; plP: 44). Groups were well balanced in respect to median age (75 vs 74 yrs); WHO PS (0 in both); baseline PSA (52 vs 44 ng/ml); bone disease (87% vs 84%) Gleason score 7 (58% vs 52%); prior treatment. At a median follow-up time of 29 mos (26–32), overall 77 pts progression and 51 died. PSA resp was recorded in 16% and 11% of pts in GP and plP groups. Median time to progression was 4.0 (3.5–4.5) and 4.5 (3.5–5.0) mos, respectively. In both groups, median PSA level increased during the first 8 wks of treatment (GP:13%; plP: 32%) while it decreased thereafter. Median time to death was 26.5 (16–37) and 20.5 (14–27) mos in the GP and plP groups, respectively (HR: 0.69, 0.39–1.23; p=.2). However, OS of pts given either early or delayed treatment with G was significantly longer (26.5 vs 17.5 mos; HR: 0.49, 0.28–0.87, p=.01). This advantage was maintained also after multivariate analysis by Gleason score, baseline PSA, Hb and PAL, WHO PS and pain score. AEs (any grade) occurred in 19 pts in each arm. However diarrhea and skin rash were more common in the GP group (12% vs 0% and 14% vs 2%, respectively). Conclusions: G when combined to P showed a moderate toxicity, achieved PSA control and prolonged pts survival. The efficacy of GP in HRPC warrants to be further investigated. [Table: see text] No significant financial relationships to disclose.

The repercussions on the venous wall of the creation of 20 artero-venous anastomoses (AVA) between the femoral artery and vein of the rat have been evaluated. The rats were killed 7, 15, 30, and 90 days after AVA, and AVAs were examined by optical microscopy and by scanning electronic microscopy. Deposits of whitish material that nearly completely occluded the venous lumen were seen, especially in the group studied longer than 90 days. These venous wall lesions, which resemble arteriosclerotic lesions, must be attributed to the new hemodynamic situation created by the AVA. The implications of such findings for the long-term validity of venous graft in vascular microsurgery and the long-term patency of the AVA in hemodialyzed children are discussed.

Background When treating bladder cancer patients, the most significant problems usually concern cases with high-grade non-muscle-invasive carcinoma, and a better understanding of which patients would benefit from early radical cystectomy is urgently needed. The uropathology community is seeking more user-friendly approaches to distinguishing between T1 cancers exhibiting different types of clinical behavior. Methods After a retrospective review, we selected a group of 314 patients who underwent transurethral resection of the bladder (TURB) and were diagnosed with high-grade urothelial carcinoma staged as T1. Three different substaging systems were applied: one was the anatomy-based T1 a/b; and two involved micrometric thresholds of either 0.5 mm of invasion (as proposed by van Rhijn et al.), or 1 mm of invasion (as proposed in the present study). Early reTUR (repeated transurethral resection) was performed in 250 patients, and the same substaging approaches were applied to cases of T1. Results It proved feasible to apply the 1 mm substaging system in 100 % of cases, the van Rhijn system in 100 %, and the anatomy-based method (T1 a/b) in 72.3 % of cases. At a mean follow-up of 46 months, the recurrence-free survival rate was significantly better (p