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.

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.

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.

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.

An experimental study of the effect of ischemia on testicular structure in the rat. Efficacy of intravenous inosine.

The damages caused by experimental testicular ischemia lasting 60 minutes have been examined in the rat. The histologic alterations of the germinal epithelium and of the tunica propria are studied, using semi-thin sections stained with 1% toluidine blue. The results show that a testicular ischemia of 60 minutes causes damages to the testicular structures. These damages cannot be prevented or avoided by either surface cooling or cold perfusion; however, intravenous inosine prior to ischemia has a protective effect.

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.

Long-term results with the Gn-RH analogue, buserelin, in metastatic prostate cancer.

LH-RH analogues have come into use to suppress the synthesis of testosterone by the testes and to induce palliation in advanced prostate cancer. Twenty-one patients were treated with buserelin (Hoe 766), and 19 were evaluable. Stages of disease were D1-D2. Seventeen patients responded to treatment, 3 patients are still in partial response, and 16 underwent progression. The median time to progression was 12 months (range, 3-36), and the median follow-up time was 10 months (mean, 25.4; range, 5-48).

Breast cancer metastases of the urinary bladder.

Two patients with breast ductal carcinoma metastases of the bladder are reported. Macrohaematuria was not present at the time of diagnosis. The time interval between surgery for primary carcinoma and detection of bladder metastases was remarkably long in both cases (63 and 164 months).

[Extracorporeal shockwave lithotripsy: treatment of choice in ureteral calculi]. / Litotrissia extracorporea ad onde d'urto: prima linea terapeutica per la calcolosi ureterale.

Extracorporeal shock wave lithotripsy represents the therapy of choice for reno-ureteral stone disease being resolutive in more than 85% of cases. This procedure can be successfully applied to ureteral stones providing appropriate preoperative cystoscopic manipulations and a correct positioning of the patient on the stretcher of the lithotripter. We hereby report our experience in 119 patients with ureteral lithiasis submitted to extracorporeal shock wave lithotripsy with a 98% success rate.

[Immunotherapy with subcutaneous recombinant IL-2 and interferon combined with surgery in advanced stage carcinoma of the kidney]. / Immunoterapia con IL-2 sottocutanea ricombinante ed interferone associata a chirurgia nel carcinoma del rene in stadio avanzato.

Twelve consecutive patients with metastatic renal cell carcinoma were submitted to an integrate treatment plan of immunotherapy with subcutaneous IL-2 and IFN and radical surgery in a pilot study. Partial response were observed in 2 patients, stable disease in 5 patients and progression of disease under treatment were observed in 5. Two RP were maintained for 12 and 18+ months and 1 SD is maintained at 12+ months. Treatment was well tolerated without significant toxicity. Integrated radical surgery and immunotherapy with s.c. IL-2 and IFN can produce occasionally protracted clinical responses.

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

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

[Extrarenal angiomyolipoma: vascular, lymphonodal, and perirenal localization. Report of 4 cases]. / Angiomiolipomi extrarenali: localizzazioni vascolari, linfonodali e perirenali. Descrizione di 4 casi.

Angiomyolipomas are rare renal tumors considered benign even though evidences of occurrence of the disease in lymphnodes and vascular structures as well as in a variety of distant sites, such as the liver, the uterus, the nasal cavity and others, have occasionally been reported. We describe one case of late lesion of angiomyolipoma within the wall of the inferior bronchial artery, two cases of lymphnodes involvement and one case of angiomyolipoma extending into the perirenal fat.

[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.

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.