To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 ((11)C) or Fluorine-18 ((18)F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding (11)C-choline or (18)F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to (18)F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and (18)F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to (18)F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.
BACKGROUND: Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials (RCTs) involving over 3000 patients.
OBJECTIVES: To conduct a systematic review and meta-analysis of individual patient data to evaluate the effect of neoadjuvant chemotherapy on survival in patients with this invasive bladder cancer.
SEARCH STRATEGY: MEDLINE and Cancerlit searches were supplemented with information from registers and by hand searching meeting proceedings and also by discussion with relevant trialists and organisations. These have been regularly updated until June 2003.
SELECTION CRITERIA: Trials that aimed to randomise patients with biopsy proven invasive (i.e. clinical stage T2 to T4a) transitional cell carcinoma of the bladder to receive local definitive treatment with or without neoadjuvant chemotherapy were eligible for inclusion.
DATA COLLECTION AND ANALYSIS: We collected, validated and re-analysed updated data on all randomised patients from all available randomised trials, including 3005 patients from 11 RCTs. For all outcomes, we obtained overall pooled hazard ratios using the fixed effects model. To explore the potential impact of trial design we pre-planned analyses that grouped trials by important aspects of their design that might influence the treatment effect. To investigate any differences in effect by pre-defined patient subgroups we used a stratified logrank analysis on the primary endpoint of survival.
MAIN RESULTS: These results include data from one extra trial and so update those in the original publication ABC 2003. Platinum based combination chemotherapy showed a significant benefit on overall survival with a combined hazard ratio (HR) 0.86 (95% CI 0.77 to 0.95, P = 0.003); 14% reduction in the risk of death; 5% absolute benefit at 5 years (95% CI 1% to 7%); overall survival increased from 45% to 50%. This effect was observed irrespective of the type of local treatment and did not vary between subgroups of patients. The HR for all trials, including those that used single-agent cisplatin, tended to favour neoadjuvant chemotherapy (HR= 0.89, 95% CI 0.81 to 0.98, P = 0.022). Although platinum based combination chemotherapy was beneficial, there was no clear evidence to support the use of single-agent platinum, indeed there was significant difference in the effect between these groups of trials (P = 0.029).
AUTHORS' CONCLUSIONS: This improvement in survival encourages the use of platinum based combination chemotherapy for patients with invasive bladder cancer.
OBJECTIVES: To compare the therapeutic efficacy of intravesical bacille Calmette-Guérin (BCG) with mitomycin C (MMC) on progression of Stage Ta and T1 bladder carcinoma.
METHODS: Combined published and unpublished data from comparative studies on BCG versus MMC in superficial bladder carcinoma were analyzed, considering possible confounding factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as the primary effect size estimate. Tumor progression was defined as progression to a higher tumor stage or the development of metastatic disease.
RESULTS: In nine eligible clinical trials, 1277 patients were treated with BCG and 1133 with MMC. Within the overall median follow-up of 26 months, 7.67% of the patients in the BCG group and 9.44% of the patients in the MMC group developed tumor progression. In all nine individual studies and in the combined results, no statistically significant difference in the ORs for progression between the BCG and MMC-treated groups was found (combined OR = 0.77; 95% CI 0.57 to 1.03; P = 0.081). In the subgroup with BCG maintenance, the combined result of the five individual studies showed a statistically significant superiority of BCG over MMC (OR = 0.66; 95% CI 0.47 to 0.94; P = 0.02). In the four studies without BCG maintenance, the combined result indicated no statistically significant difference between the two treatments (OR = 1.16; 95% CI 0.65 to 2.07; P = 0.612). Potential confounders, such as tumor risk status, duration of follow-up, BCG strain, BCG and MMC treatment regimen, and year of publication did not significantly influence these results.
CONCLUSIONS: The results demonstrated statistically significant superiority for BCG compared with MMC for the prevention of tumor progression only if BCG maintenance therapy was provided.
PURPOSE: We compare the therapeutic efficacy and toxicity of intravesical bacillus Calmette-Guerin (BCG) with mitomycin C on recurrence of stages Ta and T1 bladder carcinoma.
MATERIALS AND METHODS: Combined published and unpublished data from comparative studies on BCG versus mitomycin C for superficial bladder carcinoma considering possible confounding factors were analyzed. Odds ratio (OR) and its 95% CI were used as primary effect size estimate. Toxicity data were evaluated descriptively.
RESULTS: In 11 eligible clinical trials 1,421 patients were treated with BCG and 1,328 were treated with mitomycin C. Within the overall median followup time of 26 months 38.6% of the patients in the BCG group and 46.4% of those in the mitomycin C group had tumor recurrence. In 7 of 11 studies BCG was significantly superior to mitomycin C, in 3 studies no significant difference was found, while in 1 study mitomycin C was significantly superior to BCG. An overall statistically significant superiority of BCG versus mitomycin C efficacy in reducing tumor recurrence was detected (OR 0.56, 95% CI 0.38 to 0.84, p = 0.005). In the subgroup treated with BCG maintenance all 6 individual studies showed a significant superiority of BCG over mitomycin C (OR 0.43, 95% CI 0.35 to 0.53, p <0.001). In 4 of the 5 studies with reported data on toxicity BCG associated cystitis was significantly more frequent than in the mitomycin C group (53.8% versus 39.2%). The combined cystitis OR was 1.81 (95% CI 1.48 to 2.23, p <0.001). The OR for cystitis in the BCG maintenance group did not significantly differ from that in the nonmaintenance therapy group.
CONCLUSIONS: The results suggest superiority of BCG over mitomycin C for prevention of tumor recurrences in the combined data and particularly in the BCG maintenance treatment subgroup, irrespective of the actual (intermediate or high) tumor risk status. The toxicity with BCG is higher but does not differ between BCG maintenance and nonmaintenance groups.
To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 ((11)C) or Fluorine-18 ((18)F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding (11)C-choline or (18)F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to (18)F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and (18)F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to (18)F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.
