How Did We Obtain Complete Remission in Patients Who Had Metastatic Renal Cancer in the Era of Targeted Therapies?

BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has been transformed by the use of targeted therapies, ablative therapies and improved surgical techniques. The objective of this study was to identify therapeutic strategies that resulted in complete remission (CR) and to assess survival of patients in CR. METHODS: In a prospective database, we included all patients treated for mRCC at a university hospital between 2007 and 2015. CR was defined as the absence of metastasis after a full-body computed tomographic scan. RESULTS: We treated 77 patients with mRCC and experienced a CR in 22 (29 %) patients. Patients in CR had, respectively, synchronous and metachronous metastases in 7 (32 %) and 15 (68 %) cases and unique and multiple metastases in 4 (18 %) and 18 (82 %) cases. All patients were treated with cytoreductive nephrectomy and 21 (96 %) had metastasectomy or percutaneous ablation of their metastases. One patient had a CR after systemic treatment with sunitinib. After a median (range) follow-up since metastatic diagnosis of 35 (1-89) months, 12 patients (55 %) had disease recurrence. The median (range) duration of CR before recurrence was 14 (1-39) months. After recurrence, a new CR was obtained in 7 patients (58 %). At the end of follow-up, 16 patients (73 %) were still in CR, 5 (23 %) were undergoing medical treatment, and 1 patient died during the postoperative course. CONCLUSIONS: In the era of targeted-therapies, CRs were obtained with multimodal treatment of metastatic kidney cancer. All patients in CR had a nephrectomy and almost all of them had multiple metastasectomies.

Germline genetic variations at 11q13 and 12p11 locus modulate age at onset for renal cell carcinoma.

PURPOSE: Few risk factors have been identified for renal cell carcinoma. We performed a validation study in a population with a European background to identify the most significant variants previously identified in association with renal cell carcinoma risk. MATERIALS AND METHODS: We performed a case-control validation study after recruiting 463 controls and 463 patients with a histologically confirmed diagnosis of clear cell renal cell carcinoma. For each patient and matched control we genotyped 8 single nucleotide polymorphisms selected from previous studies to evaluate the association between candidate single nucleotide polymorphisms and renal cell carcinoma susceptibility. RESULTS: After adjusting for patient age, gender, smoking status and body mass index the AG + AA genotypes from rs7105934 (11q13) were associated with a decreased risk of renal cell carcinoma (OR 0.50, 95% CI 0.33-0.75, p = 0.001) and the AC + CC genotypes from rs1049380 (ITPR2) were associated with an increased risk (OR 1.66, 95% CI 1.28-2.16, p <0.001). Kidney cancer developed at an older age in patients carrying the dominant risk allele A for rs7105934 (mean age at diagnosis 73.1 vs 68.9 years, p = 0.002) and at a younger age in those carrying the dominant allele C for rs1049380 (mean 68.1 vs 70.8 years, p = 0.005). CONCLUSIONS: In what is to our knowledge the first validation study of the main 8 single nucleotide polymorphism variants associated with renal cell carcinoma susceptibility we confirmed the association of 2 single nucleotide polymorphisms with the risk of renal cell carcinoma. Each variant influenced patient age at disease diagnosis.

Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.

PURPOSE: The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated. PATIENTS AND METHODS: The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers. RESULTS: The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients. CONCLUSION: This association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.