Estimates of prostate cancer burden in Italy.

Age-standardized incidence rates of prostate cancer (PC) sharply increased during the period 1990-2005 in Italian areas covered by cancer registries, while corresponding mortality rates remained nearly constant. The latest observations have reported on a reversal of the incidence trend with decreasing values after 2005. We provided incidence, mortality, and prevalence estimates at national and geographical area levels, together with time projections up to the year 2020. We applied the MIAMOD method, using as input national mortality data for the years 1970-2010 and population-based survival data for the period of diagnosis (1985-2002). We assumed relative survival of prostate cancer remained constant after the year of diagnosis (2005). The age-standardized incidence rates of PC were estimated to increase during the period 1984-2005, from 31 per 100,000 in 1984 to 93 per 100,000 in 2005. From 2005 onwards, the estimated rates declined to 71 in 2015 and to 62 in 2020. Age-standardized mortality rates slightly increased from 1970 up to about 19 per 100,000 in 1999 and then started to decrease with an estimated reduction of about 2.3% per year. Mortality projections indicated a continuing reduction, with a predicted age-standardized rate of about 12 per 100,000 in 2020. Prevalence was estimated to continuously increase up to a crude prevalence value of 1.2% in the year 2020. The results indicate that the epidemic peak of PC was reached around the year 2005 followed by declining incidence rates, while a substantial decrease in mortality, starting during the early 2000s, is expected to continue during the 2010s.

Radiotherapy or chemotherapy for clinical stage IIA and IIB seminoma: a systematic review and meta-analysis of patient outcomes.

BACKGROUND: Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma. PATIENTS AND METHODS: A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only. RESULTS: Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT [0.11, 95% confidence interval (CI) 0.08-0.14, P for heterogeneity = 0.096, I(2) = 38%] and CT groups (0.08, 95% CI 0.01-0.15, P for heterogeneity <0.001, I(2) = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06-0.17) while it was 0.05 (95% CI 0-0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01-0.02) in the RT group and 0.02 (95% CI 0.003-0.04) in the CT group. CONCLUSIONS: Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.

The clinical use of statistical permutation test methodology: a tool for identifying predictive variables of outcome.

OBJECTIVES: To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). METHODS: A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysis of their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. The patients were included in a comprehensive database with medical history and clinical and pathological data. Five-year survival was used as the dependent variable, and p values were corrected for multiplicity using a closed testing procedure. The newer nonparametric approach was used to evaluate the prognostic importance of the variables. All of the analyses were performed using routines developed in MATLAB© and the significance level was set at α = 0.05. RESULTS: A significant prognostic predictive value (p < 0.01) for tumor clinical staging, hydronephrosis, tumor pathological staging, grading, presence of concomitant carcinoma in situ, regional lymph node involvement, corpora cavernosa invasion, microvascular invasion, lymphatic invasion and prostatic stroma involvement was found. CONCLUSIONS: The NPC test could handle any type of variable (categorical and quantitative) and take into account the multivariate relation among variables. This newer methodology offers a significant contribution in biomedical studies with several endpoints and is recommended in presence of non-normal data and missing values, as well as solving high-dimensional data and problems relating to small sample sizes.

PF-03446962, a fully-human monoclonal antibody against transforming growth-factor ß (TGFß) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial.

Despite a compelling preclinical rationale for the use of anti-angiogenic drugs in urothelial cancer (UC), short-living responses have been observed in clinical trials. PF-03446962 is a novel monoclonal antibody against Activin Receptor-Like Kinase-1 (ALK1), a type I subclass of the TGFß receptor, with dose-dependent anti-angiogenic activity. An open label, single-group, phase 2 trial of PF-03446962 was conducted in salvage setting. Patients failing at least one chemotherapy regimen were eligible. Design provided PF-03446962 10 mg/Kg intravenously fortnightly until disease progression (PD) or unacceptable toxicity. Two-month progression-free survival (PFS) was the primary endpoint. The trial was registered with ClinicalTrials.gov, number NCT01620970. Fourteen patients were enrolled from October 2012 to July 2013. Median age was 64 years (interquartile range [IQR]: 58.2-69.5), 9 patients had a Bellmunt score of 1-2, median number of prior drugs was 3. One stable disease and 13 PD were recorded and the study met the futility stopping rule of interim analysis. Median PFS was 1.8 months (95 %CI, 1.4-2.0). After a median follow up of 7.4 months (IQR 4.5-10.9), 8 patients are alive. Median overall survival (OS) was 8 months (95 %CI, 2.9-not estimable). Most common toxicities were thrombocytopenia (G1-2 in 5 cases, persistent G3 in one, with 3 dose delays and 1 dose interruption), fatigue and abdominal pain (G1-2 in 4 cases each). Impairment of quality of life (ESAS score) was observed as well as an increase from baseline to +2 month median levels of vascular endothelial growth factor (VEGF) and interleukin-8. PF-03446962 had no activity as single drug in refractory UC and we do not recommend further investigation outside of the combination with agents targeting the VEGF receptor axis.

Incidence and survival of rare urogenital cancers in Europe.

BACKGROUND: The RARECARE project aims at increasing knowledge of rare cancers in Europe. This manuscript describes the epidemiology (incidence, prevalence, survival) of rare urogenital cancers, taking into account the morphological characterisation of these tumours. METHODS: We used data gathered by RARECARE on cancer patients diagnosed from 1995 to 2002 and archived in 64 European population-based cancer registries, followed up to December 31st, 2003 or later. RESULTS: The annual number of males that develop penile cancer in the EU is estimated at 3100, which is equivalent to an age standardised rate (ASR) of 12 per million males. The 5-year relative survival rate is 69%, while squamous cell carcinoma is the predominant morphological entity. Each year around 650 persons in the EU develop cancer of the urethra and 7200 develop cancer of the renal pelvis or ureter (RPU). The ASR for cancer of the urethra and RPU is 1.1 (males 1.6; females 0.6) and 12 (males 16; females 7) per million inhabitants, respectively. The 5-year relative survival rate for cancer of the urethra and RPU is 54% and 51%, respectively. Transitional cell carcinoma is the predominant morphological entity of cancer of the urethra and RPU. CONCLUSIONS: In view of the low number of cases and the fact that one third to one half of the patients die of their disease, centralisation of treatment of these rare tumours to a select number of specialist centres should be promoted.

Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study.

BACKGROUND: A number of elderly cancer patients do not receive standard surgery for solid tumors because they are considered unfit for treatment as a consequence of inaccurate estimation of the operative risk. To tailor treatment to onco-geriatric series, oncologists are now beginning to use a comprehensive geriatric assessment (CGA). This study investigates the value of an extended CGA in assessing the suitability of elderly patients for surgical intervention. PATIENTS AND METHODS: Preoperative assessment of cancer in the elderly (PACE) incorporates validated instruments including the CGA, an assessment of fatigue and performance status and an anaesthesiologist's evaluation of operative risk. An international prospective study was conducted using 460 consecutively recruited elderly cancer patients who received PACE prior to elective surgery. Mortality, post-operative complications (morbidity) and length of hospital stay were recorded up to 30 days after surgery. RESULTS: Poor health in relation to disability (assessed using the instrumental activities of daily living (IADL)), fatigue and performance status (PS) were associated with a 50% increase in the relative risk of post-operative complications. Multivariate analysis identified moderate/severe fatigue, a dependent IADL and an abnormal PS as the most important independent predictors of post-surgical complications. Disability assessed by activities of daily living (ADL), IADL and PS were associated with an extended hospital stay. CONCLUSION: PACE represents a valuable tool in enhancing the decision process concerning the candidacy of elderly cancer patients for surgical intervention and can reduce inappropriate age-related inequity in access to surgical intervention. It is recommended that PACE be used routinely in surgical practice.

Pre-operative assessment of cancer in the elderly (PACE): a comprehensive assessment of underlying characteristics of elderly cancer patients prior to elective surgery.

BACKGROUND: Cancer is a disease that particularly affects the elderly and, although surgery is the first treatment choice, many elderly cancer patients do not receive standard surgery because they are considered unfit for treatment due to an inaccurate estimation of operative risk. Pre-operative Assessment of Cancer in the Elderly (PACE) was developed in order to address the need to provide detailed information about the functional reserve of the elderly cancer patient to aid individualised management. METHODS: PACE incorporates a battery of validated instruments including the Comprehensive Geriatric Assessment (CGA), Brief Fatigue Inventory (BFI), Eastern Cooperative Oncology Group Performance Status (ECOG-PS), and American Society Anesthesiologists (ASA) grade. An international prospective study was conducted with 460 consecutive elderly cancer patients (216 breast, 146 GIT, 71 GUT, 27 other) receiving PACE prior to receiving elective surgery. RESULTS: Three hundred and eighty four patients (83.4%) were observed to have at least one co-morbidity; the most common being hypertension (n=246, 53.5%). More than two thirds of the patients had good functional and mental status according to PACE. After adjusting for age, sex and type of cancer, six of the seven items of PACE were found to be significantly associated with co-morbidities (according to the Satariano's Index of Co-morbidities (SIC)). A multivariate analysis identified IADL, BFI and ASA to be the most important instruments in explaining SIC. DISCUSSION: PACE has been effectively used to describe the functional capacity and health status in an international cohort of elderly cancer patients. The majority of PACE instruments have been found to be significantly associated with co-morbidities (SIC) and can distinguish between type and severity of cancer. PACE represents a useful tool in evaluating onco-geriatric fitness for surgery.

[Recovery of urinary incontinence after retropubic radical prostatectomy. Results in 100 patients]. / Ripresa della continenza urinaria dopo prostatectomia radicale retropubica. Risultati in 100 pazienti.

AIM OF THE STUDY: To shorten the time to recovery of full urinary continence after radical retropubic prostatectomy and to increase the postoperative continence rate. MATERIALS AND METHODS: One hundred and five consecutive patients were submitted to radical retropubic prostatectomy for prostate cancer, with curative intent, focusing our attention on three steps of the operation. First, to achieve a complete control of bleeding from the dorsal vein complex and to perform a minimal touch dissection of the urethral stump; second, to perform a conservative dissection of the bladder neck, and, third, to implement a vascular type, watertight, vesico urethral anastomosis. Continence was assessed 24 hours after catheter removal and at monthly follow up visits until full recovery and graded as dry if no dropping was visible and the patient was able to interrupt the urinary stream during micturition; stress incontinence, if any dropping was observed during abdominal strain between micturitions; and wet, if uncontrollable dropping occurred, and the number of pads needed per day recorded. RESULTS: At a median follow-up time of 18 months, range 6 to 30, a total of 87 of 100 evaluable patients (87%) resulted as dry; 10 patients (10%) resulted as having a variable degree of stress incontinence needing one to three pads per day, and 3 patients (3%) resulted as wet. In 41 of the 87 dry patients (47.1%) continence was achieved within the first day from catheter removal, and in a median time of 4 weeks, range 2 to 16 in the remaining 46 patients (52.9%). CONCLUSIONS: The results of total continence rate of the present study seem to compare to the recent literature except for the time to full recovery which is shorter; it is difficult to identify the contribution of each single surgical step.

EGFr and c-erB2mRNA expression in urinary bladder superficial carcinomas.

AIM: The biological behaviour of superficial type transitional carcinomas of the urinary bladder can not be predicted. To try to differentiate those tumors that will present aggressive behaviour with infiltrative recurrences from those that will not, we studied, at the mRNA level, the expression of two membrane proteins, EGFr and c-erbB2, and of k-ras oncogene. METHODS: The mRNAs relative quantitation as performed, after RT-PCR, from histological sections cut from formalin-fixed and paraffin-embedded tissues. Twenty-three patients with urinary bladder transitional carcinoma have been studied for EGF-receptor, c-erbB2 and k-ras oncogene. The expression has been correlated with the outcomes of the follow-up period (infiltrative or superficial recurrences). RESULTS: The mRNA or EGFr was in average more expressed in tumors that continue to be superficial in the relapses, but for c-erbB2 the level of mRNA was similar in both, the more and less aggressive groups. The expression of k-ras was higher in cases associated with more infiltrative tumor relapses. CONCLUSIONS: In this preliminary study we did not identify any specific marker that can clearly predict the prognosis of superficial type transitional carcinoma of the urinary bladder; only k-ras expression is connected in some cases with the aggressiveness of the tumors. The expression of EGFr gave us intriguing results, it is in fact higher in the superficial carcinomas that do not tend to become infiltrative of the urinary bladder wall.

Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone.

OBJECTIVE: Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone. MATERIAL AND METHODS: The study including 14 consecutive metastatic prostate cancer patients with poor clinical conditions (median age: 70.5 years; median PS: 50%), refractory or resistant to a previous therapy with the LHRH analogue triptorelin alone. Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in the evening every day until progression, starting 7 days prior to triptorelin. RESULTS AND CONCLUSIONS: A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 patients with persistent thrombocytopenia prior to study. Mean serum levels of both PRL and IGF-1 significantly decreased on therapy. Finally, a survival longer than 1 year was achieved in 9/14 (64%) patients. This preliminary study would suggest that the concomitant administration of the pineal hormone MLT may overcome the clinical resistance to LHRH analogues and improve the clinical conditions in metastatic prostatic cancer patients.

Effects of cis-platinum and luteinizing hormone releasing hormone analogues on rat spermatogenesis. A morphologic and flow cytometric study.

OBJECTIVE: To evaluate morphologically and flow cytometrically the effects of cis-platinum (cis-diaminedichloroplatinum [CDDP]) administered acutely and chronically with and without gonadotropin releasing hormone analogue (LRA) pretreatment on adult rats to verify the feasibility of protecting the spermatic epithelium before chemotherapy. STUDY DESIGN: Six groups of adult Wistar rats were studied: 2 were treated with an LD50 dose of CDDP in single and 2 in multiple administrations, 1 of each was pretreated with LRA and 1 LRA control and one untreated group were also evaluated. Relative frequency of spermatogenic phases, qualitative alterations, Johnsen's score and percentage of cells in each DNA region were determined. RESULTS: Acute CDDP treatment reduced spermatids, spermatozoa and haploid cells. Chronic CDDP treatment induced in some rats a reduction in tetraploid cells and in others an increase associated with morphologically abnormal spermatids and cells showing aberrant hypodiploid content in analogy to all chronic CDDP LRA-pretreated animals. CONCLUSION: Single-dose CDDP reduces spermatids by killing rapidly cycling spermatogonia and inducing alterations in maturation; in repeated doses, more marked reductions in spermatogonia are seen, followed by a compensatory proliferation of residual stem cells with generation of cells with an aberrant DNA content. These alterations are not prevented by LRA treatment sufficient to determine inhibition of serum testosterone levels.

Antibiotic prophylaxis in prosthetic penile surgery: critical assessment of results in 75 consecutive patients.

OBJECTIVE: Antibiotic prophylaxis in prosthetic surgery was administered prospectively according an original protocol. Routine pre-operative preparation included also scrupulous, repeated disinfection of the skin of the genital and perineal region. METHODS: Vancomycin 500 mg i.v. every 6 h on the day of surgery and gentamicin 1 mg/kg i.v. every 8 h on the day of surgery and for the following 48 h were administered to 75 consecutive patients. Overall 87 prosthetic devices were implanted. The patients were evaluated at 6 weeks and at 6 months after surgery. RESULTS: No infection was observed. CONCLUSION: Support from this study to antibiotic prophylaxis in penile prosthetic surgery is uncertain. The importance of scrupulous routine pre-operative preparation is probably underestimated.

Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL-2) and alpha-interferon (A-IFN) for stage D3 prostate carcinoma failing second-line hormonal treatment.

Immunotherapy with subcutaneous rIL-2 and alpha IFN was administered to stage D3 prostate cancer patients after failure of secondary treatment with oral estramustine phosphate. Of a total of 15 patients, 2 are in partial response, with estramustine maintained after 44+ and 36+ weeks, respectively. Response to estramustine was observed initially in 7 of 13 patients, with a median duration of 12 weeks (range 8-20). No response to estramustine was observed in the remaining 6 patients. After the failure of estramustine, 13 patients were treated with immunotherapy. After the first cycle, progression of disease no therapy was given to those patients. A reduction of PSA levels was observed during the first cycle in 2 patients (15.3%); levels subsequently increased during the second cycle of treatment. A partial response was observed in 4 patients (30.7%), with a reduction of PSA levels in 3. The duration of response was 28 and 32 weeks in 2 patients who survived after failure for 18 and 21 weeks, respectively. Two patients are still alive, with continued partial response at 62+ and 42+ weeks. Side effects were represented mainly by a flu-like syndrome, associated with fever and nausea in all patients. The serum concentration of IL-10 was measured in 8 patients under study and in 11 matched controls. Levels higher than mean + 2D of controls before, during, or after immunotherapy were correlated with treatment failure, whereas levels below 6 ng/ml were encountered among the patients who showed a clinical response and a reduction of PSA during treatment. Within the limitations of this pilot study, it appears difficult to distinguish between a spontaneously slowly progressing disease and a true response to therapy.

Up-front intravesical chemotherapy for low stage, low grade recurrent bladder cancer.

PURPOSE: We evaluated the ablative and prophylactic potential of short schedule, up-front topical chemotherapy on low stage and grade recurrent bladder tumors. MATERIALS AND METHODS: The study design consisted of 4 weekly instillations followed by transurethral resection during week 5. Mitomycin C was administered initially and mitoxantrone was administered following the same schedule if disease recurred during followup. RESULTS: After up-front mitomycin C, 29 of 42 patients (69%) had a complete response with no need for transurethral resection, whereas residual disease was resected in the remaining 13 (31%). Disease recurred during followup in 22 of the 42 patients (52.4%), who were then treated with up-front mitoxantrone with a complete response in 14 (63.7%). Residual disease was resected in 8 patients (36.3%) with progression to grade 3 in 2. CONCLUSIONS: Short schedule intravesical chemotherapy can completely ablate small volume recurrent superficial bladder cancer in a relevant number of patients but it is not adequate prophylaxis.

Renal angiomyolipoma with extrarenal involvement--in vascular, lymph-node and perirenal tissue. Reports of four cases.

Extrarenal involvement was found in four cases of renal angiomyolipoma. In one case the wall of the inferior right bronchial artery was infiltrated, lymph nodes were involved in two cases and the perirenal fat in one case. Extrarenal extension does not seem to alter the prognosis of renal angiomyolipoma. Expectant treatment of this rare condition therefore appears to be warranted.

Short schedule intravesical mitomycin preceding transurethral resection for recurrent Ta-T1, G1-G2 bladder cancer.

AIMS AND BACKGROUND: Intravesical instillations commonly follow resection, when all visible lesions have been removed, making impossible any direct assessment of efficacy. The study was conceived to evaluate the ablative effect on the tumor and the efficacy in reducing the risk of recurrence of short schedule intravesical chemotherapy administered before endoscopic resection. STUDY DESIGN: Four weekly intravesical instillations of mitomycin C followed by transurethral resection (TUR) were administered to 31 patients with recurrent small volume superficial bladder cancer. RESULTS: At TUR no evidence of disease was found in 22 patients (70.9%) and residual disease in the remaining 9 (29.1%). At a median follow-up of 15 months (range, 3-33) 16 of 31 patients (51.6%) had recurrence of disease. The treatment was well tolerated. CONCLUSIONS: Short-schedule intravesical chemotherapy can completely ablate small volume recurrent superficial bladder cancer in a relevant number of patients but is probably not sufficient to obtain long-term prophylaxis.

Video laparoscopic excision of a seminal vesicle cyst associated with ipsilateral renal agenesis.

A 6 cm. cystic right seminal vesicle was successfully removed using operative laparoscopy. Advantages of the laparoscopic approach over open surgery include excellent exposure of the deep pelvic structures and rapid convalescence. Among the disadvantages are the potential complications associated with laparoscopic transperitoneal access.

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.

Five-year results of neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy plus radical cystectomy in locally advanced bladder cancer.

Neoadjuvant systemic cisplatin, methotrexate and vinblastine chemotherapy has been used in the treatment of 69 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0). Sixty patients were evaluable for response at a median follow-up of 48 months. Preoperative resection of the tumor was purposely avoided in order to keep a marker lesion. After planned radical cystectomy, pathological complete responses (pCRs) and partial responses (pPRs) were documented in 5 (8.3%) and 29 cases (43.4%), respectively. These patients had a 5-year disease-free survival rate of 80%, which was statistically superior (p = 0.0013) to 35% for the remaining nonresponding patients. One patient (20%) with a pCR died of systemic disease after 14 months, while the remaining 4 patients (80%) are alive and free of disease after a median follow-up of 57 months. A higher percentage of pCRs and pPRs was observed in the group of patients with stage T3b-T4 tumor (pCR 11%, pPR 63%) in contrast to the patients with stage T2-T3a disease (pCR 4.5%, pPR 45.5%), even if no significant difference in the 5-year survival rate was observed between the 2 groups. Patients with a G2 tumor before chemotherapy survived longer (5-year survival rate of 78%) than those with G3 disease (5-year survival rate of 61%), but no significant difference was achieved.