Metformin, an oral biguanide used for first-line treatment of type 2 diabetes mellitus, has attracted attention for its anti-proliferative and anti-cancer effects in several solid tumors, including prostate cancer (PCa). Liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) activation, inhibition of the mammalian target of rapamycin (mTOR) activity and protein synthesis, induction of apoptosis and autophagy by p53 and p21, and decreased blood insulin level have been suggested as direct anti-cancer mechanisms of metformin. Research has shown that PCa development and progression are associated with metabolic syndrome and its components. Therefore, reduction in the risk of PCa and improvement in survival in metformin users may be the results of the direct anti-cancer mechanisms of the drug or the secondary effects from improvement of metabolic syndrome. In contrast, some research has suggested that there is no association between metformin use and PCa incidence or survival. In this comprehensive review, we summarize updated evidence on the relationship between metformin use and oncological effects in patients with PCa. We also highlight ongoing clinical trials evaluating metformin as an adjuvant therapy in novel drug combinations in various disease settings.

Ahn HK, et al. Investig Clin Urol. 2022 Jul;63:e61. https://doi.org/10.4111/icu.20220124

This study aimed to evaluate the effect of bladder neck preservation (BNP) on long-term urinary continence after robot-assisted laparoscopic prostatectomy (RALP). We systematically searched the PubMed, Embase, and Cochrane Library databases to identify studies that assessed the difference in urinary continence and oncologic outcomes between patients who underwent RALP with BNP and those who underwent RALP without BNP. Four trials (1880 cases with BNP, 727 controls without BNP) were considered suitable for meta-analysis. BNP was associated with significantly better urinary continence outcomes at 3–4 months (odds ratio (OR), 2.88; 95% confidence interval (CI), 1.52–5.48; p = 0.001), 12 months (OR, 2.03; 95% CI, 1.10–3.74; p = 0.02), and 24 months (OR, 3.23; 95% CI, 1.13–9.20; p = 0.03) after RALP. There was no difference in the rate of overall positive surgical margin (PSM) (OR, 1.00; 95% CI, 0.72–1.39; p = 0.99) and that of PSM at the prostate base (OR, 0.49; 95% CI, 0.21–1.13; p = 0.09) between the two groups. The BNP technique during RALP leads to early return of urinary continence and long-term urinary continence without compromising the oncologic outcomes.

Limited studies have investigated the correlation between body composition and prostate cancer outcomes. We analyzed the effect of muscle mass and quality on castration-resistant prostate cancer (CRPC) outcomes. Skeletal muscle index (SMI) and skeletal muscle attenuation (SMA) were measured for 411 patients at the L3 vertebral level using computed tomography at CRPC diagnosis and were dived to low and high groups at the value of median. Analysis of the skeletal phenotypes and age (70 years) was performed to evaluate the effect of SMI and SMA. The median survival rates for patients with low and high SMI were 19 and 24 months (p = 0.015), and those with low and high SMAs were 15 and 26 months (p < 0.001), respectively. In the subgroup analysis by age, SMA was a significant prognosticator in both groups, while SMI was a significant prognosticator only in patients aged >70 years. Patients with low SMA + low SMI had the worst prognosis. Muscle characteristics seems to be a prognosticator in survival of CRPC patients and may be considered in treatment planning.

Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples from 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria.

Kim JW, et al. World J Mens Health. 2021 Jun;39:e39. https://doi.org/10.5534/wjmh.210019