Aleksandra Klim

Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Staging of Muscle-Invasive Bladder Carcinoma

PURPOSE Novel imaging modalities are needed to detect occult metastatic disease in bladder carcinoma. Patients with regional lymphatic spread could be targeted for neoadjuvant chemotherapy, and patients with distant metastatic disease could be spared the unnecessary morbidity of radical cystectomy. Herein, we report a prospective study of positron emission tomography/computed tomography (PET/CT) with [(18)F]fluorodeoxyglucose (FDG) in patients undergoing radical cystectomy for cT2-3N0M0 urothelial carcinoma of the bladder. METHODS Forty-three chemotherapy-naïve patients underwent FDG-PET/CT before planned cystectomy. All had negative conventional CT and bone scintigraphy before enrollment. Positive FDG-PET/CT was confirmed by percutaneous biopsy or open surgical exploration, whereas negative FDG-PET/CT was confirmed by complete lymphadenectomy. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were described using the Kaplan-Meier method and compared using log-rank test. RESULTS Median follow-up was 14.9 months (range, 0.4 to 46.1 months). One patient who did not undergo lymphadenectomy was excluded from the pathology data analysis (n = 42), whereas another patient who failed to return for follow-up was excluded from survival analysis (n = 42). FDG-PET/CT demonstrated a positive predictive value of 78% (seven of nine), a negative predictive value of 91% (30 of 33), sensitivity of 70% (seven of 10), and specificity of 94% (30 of 32). RFS, DSS, and OS were all significantly poorer in the patients with positive FDG-PET/CT than in those with negative FDG-PET/CT. CONCLUSION FDG-PET/CT detected occult metastatic disease in seven of 42 patients with negative conventional preoperative evaluations. PET findings were strongly correlated with survival. As such, FDG-PET/CT may help in making treatment decisions before radical cystectomy.

Association between polymorphisms in cell cycle genes and advanced prostate carcinoma.

Single nucleotide polymorphisms (SNPs) have been associated with a variety of malignancies including prostate carcinoma (PCa). Since a high percentage of PCa patients have low risk disease, of particular interest is not whether SNPs are associated with localized PCa, but whether they are associated with aggressive, potentially lethal disease. Herein, we explored the role of SNPs in cell cycle genes to determine if they were associated with advanced PCa.

Randomized Controlled Trial of Oxybutynin Extended Release Versus Placebo for Urinary Symptoms During Intravesical Bacillus Calmette-Guérin Treatment

PURPOSE Intravesical bacillus Calmette-Guérin is used to decrease recurrence rates of nonmuscle invasive urothelial carcinoma. Irritative urinary symptoms are a common side effect of treatment and frequently limit treatment tolerance. While anticholinergic medications may be used for symptom prophylaxis, to our knowledge they have not been evaluated in a randomized controlled trial. MATERIALS AND METHODS A total of 50 bacillus Calmette-Guérin naïve patients were randomized to 10 mg extended release oxybutynin daily or placebo starting the day before 6 weekly bacillus Calmette-Guérin treatments. A questionnaire assessing urinary symptoms (frequency, burning on urination, urgency, bladder pain, hematuria), systemic symptoms (flu-like symptoms, fever, arthralgia) and medication side effects (constipation, blurred vision, dry mouth) was recorded daily throughout the therapeutic course. A linear mixed repeated measures model tested the differences between each point and baseline score. RESULTS The treatment group had a greater increase in urinary frequency and burning on urination compared to placebo (p = 0.004 and p = 0.04, respectively). There were no significant differences between groups for other urinary symptoms, which increased in severity after bacillus Calmette-Guérin but concomitantly returned to baseline in both groups. The treatment group experienced increases in fever, flu-like symptoms, dry mouth and constipation compared to placebo (p <0.0001, p = 0.0008, p = 0.045 and p = 0.001, respectively). There were otherwise no significant differences in nonurinary symptoms or medication adverse reactions. CONCLUSIONS Oxybutynin increased urinary frequency and burning on urination compared to placebo in patients receiving intravesical bacillus Calmette-Guérin treatment. Our results do not support the routine use of oxybutynin as prophylaxis against urinary symptoms during bacillus Calmette-Guérin therapy.

Association of CASP8 D302H Polymorphism with Reduced Risk of Aggressive Prostate Carcinoma

Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele.

Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma

Because a significant number of patients with prostate cancer (PCa) are diagnosed with disease unlikely to cause harm, genetic markers associated with clinically aggressive PCa have potential clinical utility. Since cell cycle checkpoint dysregulation is crucial for the development and progression of cancer, we tested the hypothesis that common germ‐line variants within cell cycle genes were associated with aggressive PCa.

A PROSPECTIVE STUDY OF FDG-PET/CT FOR DETECTING OCCULT METASTATIC BLADDER CARCINOMA

INTRODUCTION AND OBJECTIVES: PET with 18F-FDG has been considered of limited value because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET associated with Computed Tomography (CT) in the staging of new diagnosed bladder cancer (BC) or in restaging of BC during follow-up after cystectomy or chemotherapy using furosemide and oral hydration to remove the excreted 18-F-FDG from the bladder. METHODS: Thirty two patients (23 male, 9 female), with histologically proven muscle invasive BC by transurethral resection of the bladder (TUR/B), were included in this prospective study. Mean age was 69 years and mean follow up was of 4,7 months (0,3-10,3). All underwent a 18F-FDG from head to the upper thighs with additional pelvic images after 1 h I.V. furosemide and oral hydration at least 3 months after TUR/B. In 25 cases a CT of thorax and abdomen with contrast medium had also been preformed within the 2 weeks prior to PET/CT. For CT scan, nodes greater than 1 cm or defined as suspicious by the radiologist were considered positive. The 18F-FDG-PET/CT lesions with metabolic activity greater than 2.5 SUV on a confirmed anatomical structure were considered positive. Imaging findings were confirmed by histology or if not possible, by imaging follow-up. RESULTS: Of the 32 patients, 26 patients were studied with 18F-FDG-PET/CT before radical cystectomy or in 2 cases only pelvic lymphadenectomy. In the same group, 19 CT were also performed. 18F-FDG-PET/CT detected 21 of the 23 bladder lesions (91,3%) and 8/15 (53,3%) pelvic node metastasis, mostly N2. False negative were a pTis and a pT4. CT detected 12 of 17 bladder lesion (70.6%) and 4 out of 9 positive nodes (44.4%). 18F-FDG-PET/CT showed prostate metabolic activity in 4 cases. In 2 cases BC invasion was histologically proven. Metabolic activity was seen in 2 para-aortic lymph-nodes (LN), 3 mediastinal LN, 2 cervical LN and 4 pulmonary nodules. All these lesions showed progression on imaging follow up. CT was negative in all prostate lesions, 1 para-aortic LN and 2 pulmonary nodules. CONCLUSIONS: This prospective series shows that 18F-FDGPET/CT with furosemide wash out of the bladder was better than conventional CT for the detection of residual tumor in the bladder, pelvic LN metastasis and prostate infiltration. Moreover PET/CT detected earlier than conventional CT distant metastasis to retroperitoneal and cervical LN and pulmonary metastasis.