Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer.

AIM: This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer. BACKGROUND: A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n = 205 [18.8%]), intermediate- (n = 450 [41.2%]), high- (n = 345 [31.6%]), and very high-risk (n = 91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74-78 Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2-120 months). RESULTS: The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20 ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20 ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively. CONCLUSIONS: The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer.

[Clinical usefulness of chlormadinone acetate as an alternative antiandrogen therapy for prostate cancer relapse after combined androgen blockade therapy].

We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen and estimated its effect. Four patients showed a > or = 50% decline in prostate-specific antigen (PSA) levels and another 4 patients showed a < 50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of < 1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level of > or = 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.

[Case of urachal cancer treated by neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin)].

A 52-year-old woman was referred to our hospital for treatment of urachal cancer. She complained of supurapubic dull pain and gross hematuria. Computed tomography and magnetic resonance imaging showed a non-papillary sessile tumor, which was located on the dome of the bladder and invaded the small intestine. The tumor was diagnosed as Sheldon's stage IIIC urachal cancer. After three courses of neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin), the tumor was reduced from 7 x 6 cm to 5.5 x 5 cm in size. Consequently, the patient underwent an en-bloc resection of the urachal tumor with the dome of the bladder and the parts of the ileum invaded by the tumor. One course of adjuvant chemotherapy (FOLFOX4) was performed. Surgical specimen revealed histologically well differentiated squamous carcinoma and invasion to the propria of the ileum. The surgical margins were negative for the cancer. For 1.5 years after the surgery, no local recurrence or distant metastasis has been observed.