Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. METHODS: Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis (DCA). RESULTS: Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), and EAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. CONCLUSIONS: The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

[Aristolochic acid nephropathy ("Chinese herb nephropathy")]. / Néphropathie aux acides aristolochiques (« néphropathie aux herbes chinoises ¼).

Aristolochic acid nephropathy is a renal disease of toxic origin characterized by a progressive interstitial fibrosis and frequently associated with urinary tract cancer. It was initially reported in Belgium after the intake of slimming pills containing root extracts of a Chinese herb, Aristolochia fangchi. In the following decades, numerous cases have been reported worldwide, particularly in Asian countries. Several experimental models of aristolochic acid nephropathy (AAN) have been designed. They confirm the causal link between AA exposure and the onset of acute and chronic renal toxicity, as well as urinary tract cancer. These experimental models offer the opportunity to study the mechanisms of renal interstitial fibrosis and carcinogenesis. In terms of public health, the history of this nephropathy demonstrates that it is mandatory to submit all "natural medicinal products" to the same controls of efficacy, toxicity and conformity applied to the classical drugs derived from the pharmaceutical producers. Any unusual observation of renal failure and/or cancer of the urinary tract should lead to a questioning about any prior exposure to AA. The confirmation of the ingestion of AA containing compounds by phytochemical analysis is not always feasible. However, the renal biopsy remains a crucial diagnostic point through the demonstration of a hypocellular interstitial fibrosis with a decreasing corticomedullary gradient, mostly in advanced cases of kidney disease. Moreover, the detection of AA-related DNA adducts within a renal or urothelial tissue sample could confirm the prior AA exposure. The persistence of these specific DNA adducts in renal tissue is very long (up to 20 years). Finally, considering the highly carcinogenic properties of AA, a systematic endo-urological screening is absolutely necessary.

Select screening in a specific high-risk population of patients suggests a stage migration toward detection of non-muscle-invasive bladder cancer.

BACKGROUND: More than 25% of bladder cancer (BC) cases are still muscle-invasive at first diagnosis. Screening is unproven to enable the detection of more non-muscle-invasive tumors. BC association with aristolochic acid nephropathy (AAN) was reported after intake of slimming pills containing Chinese herbs. OBJECTIVE: We evaluated whether a BC screening protocol in a high-risk and unique patient population had an impact on the stage of tumor presentation. DESIGN, SETTING, AND PARTICIPANTS: Forty-eight AAN-affected patients were enrolled in a screening program, establishing BC incidence during prospective screening cystoscopies and biopsies biannually for up to 10 yr. Two patients were lost to follow-up, and three refused screening after consenting. MEASUREMENTS: Patients were evaluated for presence of BC and tumor stage at diagnosis. RESULTS AND LIMITATIONS: BC was diagnosed in 25 patients (52%). Among 43 patients who underwent screening cystoscopies (median follow-up: 94 mo), 22 were first diagnosed with non-muscle-invasive BC but none with muscle-invasive tumors and none died of BC. Three women who declined follow-up were diagnosed and died with advanced metastatic disease. The limitations of our findings include the small sample size of this case series, the absence of a real control group, and the particular risk factor in these patients that differs from the usual risk factors, such as smoking or industrial chemicals. CONCLUSIONS: BC screening in high-risk groups may allow identification of tumors before muscle invasion. The optimal screening schedule and the relevance of the present findings in smoking-related BC remain to be defined.

Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.

BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.