Safety and outcomes of new generation hormone-therapy in elderly chemotherapy-naive metastatic castration-resistant prostate cancer patients in the real world.

BACKGROUND: Abiraterone acetate and enzalutamide are standard treatments for chemotherapy-naive metastatic castration-resistant prostate cancer (CN-mCRPC). The purpose of this study was to evaluate the effectiveness and safety of these medications in elderly (≥ 75 years old) compared with young CN-mCRPC patients in a real-world clinical setting. Secondarily, we explored the survival prognostic value of different anatomo-clinical factors in elderly group. METHODS: In this retrospective observational multicentre study, we included 134 consecutive CN-mCRPC patients, 64 young and 70 elderly men, who had received AA or Enz. RESULTS: We did not find significant differences in treatment duration [16.6 months, (95% CI 9-24.2 months) vs. 16.8 months (95% CI: 6.3-27.2 months); p = 0.926] and overall survival [median not reached vs. 23.3 months (95% CI 10.2-36.3 months); p = 0.131] between the young and elderly groups. In elderly group, the only predictors of overall survival with AA or Enz were good ECOG performance status and high G8 score. Adverse events of grade ≥3 was similar in elderly group (12.9%) and in the young group (15.6%). Treatment was discontinued due to AEs in 6.3% of young group and 18.6% of elderly group. CONCLUSIONS: Effectiveness and safety of treatment of CN-mRCPC with Abiraterone acetate and enzalutamide were similar in older and younger patients, although treatment discontinuation due to AEs was more frequent in the older age group. In addition to ECOG PS, assessment using specific geriatric scales as G8 screening tool could help to identify patients aged ≥75 who would most benefit from treatment with new-generation hormone therapy.

Cancer-Specific Survival Stratification Derived from Tumor Expression of Tissue Inhibitor of Metalloproteinase-2 in Non-Metastatic Renal Cell Carcinoma.

Degradation of the extracellular matrix is a prerequisite for the processes of cancer cell invasion and metastasis. The purpose of our study was to assess the association of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9) and their inhibitors (TIMP-1 and TIMP-2) with renal cell carcinoma (RCC) progression and cancer-specific survival (CSS), using immunohistochemical analysis of 60 formalin-fixed, paraffin-embedded sections of tumor tissue and normal tissue near the tumor from surgical T1-3bN0 M0 RCC specimens. Significant overexpression of MMP-2 in tumor and normal tissue was correlated with advanced stages, tumor size, sarcomatous differentiation and clinical symptoms. Overall survival was 31.7% (55.2% M0, 9.7% M1) and CSS 56.7% (100% M0, 16.1% M1) with a follow-up of 76 (5-230) months. Fuhrman grade [HR 2.87 (95% CI: 1.28-6.45); p = 0.01], tumor size [HR 1.13 (95% CI: 1.03-1.26); p = 0.009] and low TIMP-2 expression [HR 0.35 (95% CI: 0.16-0.78); p = 0.01] were independent predictive factors of CSS and stratified the patients into three groups with different rates of 10-year CSS; [100%, 73.9% and 20.5% for the good, intermediate and poor prognosis group respectively (p = 0.000006)] . This study offers strong evidence that TIMP-2 expression in tumor tissue may play a crucial role in progression and poor prognosis in human localized and locally advanced RCC.

Sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive bladder cancer in intermediate- and high-risk patients: final outcome of CUETO 93009, a randomized prospective trial.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is an effective therapy in non-muscle-invasive bladder cancer (NMIBC), but it has limitations in terms of recurrence and toxicity. OBJECTIVE: To determine whether the sequential combination of mitomycin C (MMC) and BCG is superior to BCG alone in increasing a disease-free interval (DFI). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective randomized trial including 407 patients with intermediate- to high-risk NMIBC and allocated 211 to the MMC and BCG arm and 196 to the BCG-alone arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The trial was designed to provide concurrently a power of 80% for the detection of a relative risk reduction of 35% (hazard ratio [HR]: 0.65) of disease relapse with a type I error of 0.05. Times to events were estimated using cumulative incidence functions and compared using the Cox regression model. We used the Kaplan-Meier technique to estimate survival curves. RESULTS AND LIMITATIONS: In the intention-to-treat analysis at 5 yr, DFI was significantly improved by the sequential scheme (HR: 0.57; 95% confidence interval [CI], 0.39-0.83; p=0.003), reducing the disease relapse rate from 33.9% to 20.6%. Higher toxicity was observed with the combination, even reducing the MMC dose, especially in G3 local toxicity compared with BCG with a difference of 17.4% (95% CI, 7.6-27.2; p<0.001). In recurrent T1 tumors, the potential benefit of the sequential scheme was more evident than in the remaining subgroup (18.8% vs 12.8%), with a number needed to treat of five versus eight to avoid an event and with similar toxicity. CONCLUSIONS: Although the sequential scheme is more effective than BCG alone in reducing disease relapse, due to higher toxicity it could be offered only to patients with a high likelihood of recurrence, such as those with recurrent T1 tumors. PATIENT SUMMARY: We analyzed the outcomes of a randomized trial demonstrating that in intermediate- to high-risk non-muscle-invasive bladder cancer, mitomycin C and bacillus Calmette-Guérin (BCG) reduced disease relapse compared with BCG alone but was more toxic. Consequently, it could be offered only to patients with recurrent T1 tumors. TRIAL REGISTRATION: CUETO 93009.

Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013.

BACKGROUND: Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity. OBJECTIVE: To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile. DESIGN, SETTING, AND PARTICIPANTS: Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007. INTERVENTION: Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests. RESULTS AND LIMITATIONS: A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%). CONCLUSIONS: In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone. PATIENT SUMMARY: Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment. TRIAL REGISTRATION: CUETO 98013.

Renal leiomyosarcoma.

Leiomyosarcoma (LMS) is a rare malignant tumor of smooth muscle origin that generally stems from soft tissues and uterine tissue. Although, a small percentage of these may originate from the smooth muscle or vessel walls, most of which are of venous origin. Renal leiomyosarcomas may arise from the smooth muscle fibers of renal pelvis, renal capsule or renal vessels, last one is the most frequent. We report a case of renal LMS that could be originated in the renal capsule.