AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer.

Lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with 177Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before 177Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor 177Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted. Patient summary: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA.

Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.

Smith-Magenis syndrome (SMS) is a contiguous-gene disorder most commonly caused by a deletion of chromosome 17p11.2. We report a 57 year-old man with SMS who presents bilateral renal tumors. This is most likely related to haploinsufficiency of FLCN gene, located in the deleted region, and a known tumor suppressor gene. Haploinsufficiency of FLCN causes Birt-Hogg-Dubé syndrome (BHDS), characterized by pulmonary cysts, renal and skin tumors. The present observation suggests that the follow-up of patients with SMS should also focus on possible manifestations of BHDS.

FDG-PET/CT for the preoperative lymph node staging of invasive bladder cancer.

BACKGROUND: Locoregional lymph node metastasis is an important prognostic factor in patients with bladder cancer. Multimodal treatment, depending on preoperative stage, may improve survival. The standard imaging modalities for staging (computed tomography [CT] or magnetic resonance imaging [MRI]) have an accuracy range of 70-90% for lymph node staging. A more accurate preoperative diagnostic test could improve survival rates even more. OBJECTIVE: To determine whether the use of 2-deoxy-2 [F] fluoro-D-glucose (FDG) positron emission tomography (PET) in combination with CT (FDG-PET/CT) can increase the reliability of preoperative lymph node staging in patients with nonmetastatic invasive bladder cancer (T2 or higher, M0) or recurrent high-risk superficial disease (T1G3 with or without Tis, M0). DESIGN, SETTING, AND PARTICIPANTS: Fifty-one patients underwent a preoperative FDG-PET/CT between April 2004 and December 2007. Independent of the result for lymph node status, all patients underwent a radical cystectomy and an extended lymphadenectomy. The FDG-PET/CT and CT results were compared with the definitive pathologic results. MEASUREMENTS: Among the 51 patients, 13 patients had metastatically involved locoregional lymph nodes, diagnosed on histopathology. In six patients, these nodes demonstrated increased FDG uptake on PET. In seven patients, PET/CT did not diagnose the positive lymph nodes. PET/CT was false positive in one patient. RESULTS AND LIMITATIONS: For the diagnosis of node-positive disease, the accuracy, the sensitivity, and the specificity of FDG-PET/CT were 84%, 46%, and 97%, respectively. When analysing the results of CT alone, there was accuracy of 80%, sensitivity of 46%, and specificity of 92%. The use of FDG-PET/CT is hampered by technical limitations. CONCLUSIONS: We found no advantage for combined FDG-PET/CT over CT alone for lymph node staging of invasive bladder cancer or recurrent high-risk superficial disease.

Comparison between open partial and radical nephrectomy for renal tumours: perioperative outcome and health-related quality of life.

OBJECTIVE: To compare perioperative outcome and health-related quality of life (HRQOL) after open partial and radical nephrectomy for renal tumours. METHODS: Literature search of Medline and additional references from non-Medline-indexed journals for documents concerning treatment of renal tumours, perioperative outcome, and HRQOL after radical and partial nephrectomy. RESULTS: A total of 39 references were used of which 7 discussed complications, 3 included hospital costs and length of stay, and 7 each discussed renal function and QOL. No statistical difference was found concerning perioperative complications although there seems to be a trend towards a slightly higher complication rate after partial nephrectomy. No statistical difference was reported between the two procedures concerning hospital costs and length of stay. For postoperative renal function, a higher incidence of chronic renal failure was noted after radical nephrectomy. When considering the HRQOL a benefit was found after elective partial nephrectomy. In case of mandatory partial nephrectomy the fear of recurrence and the worry about having fewer than two normal kidneys were significantly higher. CONCLUSIONS: Partial nephrectomy achieves a better HRQOL due to better preservation of renal function and overall quality of life. Considering perioperative outcome no statistical difference was found for hospital costs and length of stay. A trend towards a higher perioperative complication rate was found after partial nephrectomy.