BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) is the reference modality for detecting clinically significant prostate cancer (csPC). Biparametric MRI (bpMRI), which omits contrast, has emer...BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) is the reference modality for detecting clinically significant prostate cancer (csPC). Biparametric MRI (bpMRI), which omits contrast, has emerged as a streamlined alternative. Recent studies have demonstrated the noninferiority of bpMRI to mpMRI for csPC detection in biopsy-naïve men. We performed an updated systematic review and meta-analysis of head-to-head studies comparing bpMRI and mpMRI for csPC detection, and conducted a noninferiority analysis. METHODS: Literature databases were searched up to September 2025 for head-to-head studies. Eligible studies enrolled men with suspected PC and used biopsy or prostatectomy as the reference standard. The primary outcome was diagnostic accuracy for csPC at per-patient and per-lesion levels; detection of any PC was a secondary outcome. Noninferiority was assessed using a margin of -5% applied to paired absolute differences (bpMRI - mpMRI) in sensitivity and specificity via a random-effects model. KEY FINDINGS AND LIMITATIONS: A total of 40 studies (9403 patients) were analyzed. For csPC, the paired absolute differences were -2.3% (95% confidence interval [CI] -4.1% to -0.5%) for sensitivity, and +1.8% (95% CI -0.4% to +4.0%) for specificity, which confirm noninferiority at the patient level. At the lesion level, bpMRI was noninferior for specificity but not sensitivity, probably because of fewer studies and greater heterogeneity. CONCLUSIONS AND CLINICAL IMPLICATIONS: bpMRI is noninferior to mpMRI for csPC detection at the patient level. At the per-lesion level, noninferiority was demonstrated for specificity but not for sensitivity. Broader implementation should occur in settings with assured image quality, and further work is needed to define minimum quality-control standards required for adoption.
Nguyen PL, Kollmeier MA, Rathkopf DE
… +17 more, Hoffman KE, Zurita AJ, Spratt DE, Dess RT, Liauw SL, Szmulewitz RZ, Einstein DJ, Bubley GJ, Yu JB, An Y, Wong AC, Feng FY, McKay RR, Rose BS, Shin KY, Kibel AS, Taplin ME
BACKGROUND AND OBJECTIVE: For patients with detectable prostate-specific antigen (PSA) after radical prostatectomy, 6 mo of a GNRH agonist with salvage radiotherapy (sRT) is a standard treatment option. METHODS: FORMULA-...BACKGROUND AND OBJECTIVE: For patients with detectable prostate-specific antigen (PSA) after radical prostatectomy, 6 mo of a GNRH agonist with salvage radiotherapy (sRT) is a standard treatment option. METHODS: FORMULA-509 (NCT03141671) enrolled 345 patients with PSA ≥0.1 ng/ml and high-risk features from November 24, 2017 to March 25, 2020. Patients received sRT plus 6 mo of a GNRH agonist and randomization to bicalutamide (50 mg) or abiraterone acetate + prednisone (AAP; 1000 mg/5 mg) + apalutamide (240 mg) QD. The primary endpoint was PSA progression-free survival (PFS). A secondary endpoint was metastasis-free survival (MFS) on conventional imaging. Stratification was by PSA (>0.5 vs ≤0.5 ng/ml) and pN status (pN0 vs pN1). KEY FINDINGS AND LIMITATIONS: Median follow-up was 34 mo. AAP + apalutamide did not reach the prespecified significance level for PFS benefit in comparison to bicalutamide (hazard ratio [HR] 0.71. 90% confidence interval [CI] 0.49-1.03; stratified one-sided log-rank p = 0.063), with 3-yr PFS rates of 68.5% with bicalutamide versus 74.9% with AAP + apalutamide. The HR for MFS was 0.57 (90% CI 0.33-1.01; stratified one-sided p = 0.050) and the 3-yr MFS rates were 87.2% with bicalutamide versus 90.6% with AAP + apalutamide. A preplanned analysis by stratification factors revealed that for patients with PSA >0.5 ng/ml, AAP + apalutamide was associated with superior PFS (HR 0.50, 95% CI 0.27-0.95; 2-sided p = 0.030; 3-yr PFS 46.8% with bicalutamide vs 67.2% with AAP + apalutamide) and MFS (HR 0.32, 95% CI 0.13-0.84; 2-sided p = 0.014; 3-yr MFS 66.1% with bicalutamide vs 84.3% with AAP + apalutamide). Adverse events were consistent with the known safety profiles of the study agents, with more frequent rash and hypertension in the AAP + apalutamide arm. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study did not reveal a benefit for the overall population, but addition of AAP + apalutamide (vs bicalutamide) to sRT and ADT improved PFS and MFS in the prespecified subgroup with PSA >0.5 ng/ml.
Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic urothelial carcinoma. Encouraging clinical activity of HER2-directed ADCs, including disitamab vedotin, has been observed in earl...Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic urothelial carcinoma. Encouraging clinical activity of HER2-directed ADCs, including disitamab vedotin, has been observed in early-phase trials. Recent promising results from the RC48-C016 trial raise important questions. We discuss issues that include optimal frontline treatment selection, subsequent-line treatment sequencing, and the generalizability of the findings.
Armstrong AJ, Petrylak DP, Shore ND
… +13 more, Szmulewitz RZ, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Iguchi T, Gomez-Veiga F, Croitoru R, Wu R, Kalac M, Tang Y, Stenzl A, Azad AA
The ARCHES trial (NCT02677896) showed improved radiographic progression-free survival (primary analysis; 2018) and overall survival (prespecified analysis; 2021) with enzalutamide versus placebo, with concomitant androge...The ARCHES trial (NCT02677896) showed improved radiographic progression-free survival (primary analysis; 2018) and overall survival (prespecified analysis; 2021) with enzalutamide versus placebo, with concomitant androgen-deprivation therapy, in metastatic hormone-sensitive prostate cancer (mHSPC) patients. This post hoc analysis describes 5-yr efficacy and safety for all 1150 randomized patients (data cutoff: July 31, 2024). Patients were randomized 1:1 to receive enzalutamide or placebo (first patient randomized: March 21, 2016). After the primary analysis, ARCHES was unblinded (December 10, 2018); 65% and 32% of patients in the enzalutamide and placebo groups, respectively, enrolled in the open-label extension. After the 61.4-mo median follow-up, 5-yr survival probability was 66% with enzalutamide and 53% with placebo (median months not reached in either group; hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.58, 0.85; p < 0.001; adjusted HR: 0.64; 95% CI: 0.51, 0.75). Patients with high-volume disease who received enzalutamide lived 36 mo longer than those who received placebo (HR: 0.70; 95% CI: 0.56, 0.88). No new safety signals emerged. As this was a post hoc, non-alpha protected analysis, the overall survival p value is nominal and should be interpreted cautiously. Overall, this study provides compelling long-term data demonstrating survival benefits with enzalutamide across diverse patient subgroups to guide clinical decision-making and establish prognostic expectations in the mHSPC setting.
Hayne D, Zhang AY, Thomas H
… +24 more, Krieger L, Ischia J, Anderson P, Srivastav RK, Green W, Grummet J, Bastick PA, Beardsley EK, Blatt A, Patel M, Chan L, Mitterdorfer A, Roberts M, Sengupta S, Winter M, Marx G, Bishop C, Cheung L, Hawks C, Martin A, McCombie SP, Redfern AD, Davis ID, Stockler MR
BACKGROUND AND OBJECTIVE: Intravesical bacillus Calmette-Guérin (BCG) plus mitomycin (MM) had not been compared rigorously with BCG alone in BCG-naïve, non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Partic...BACKGROUND AND OBJECTIVE: Intravesical bacillus Calmette-Guérin (BCG) plus mitomycin (MM) had not been compared rigorously with BCG alone in BCG-naïve, non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Participants with BCG-naïve NMIBC (high-grade pTa or any grade pT1; concurrent carcinoma in situ [CIS] allowed) were assigned randomly (1:1) to either the BCG + MM or the BCG-alone group after maximal transurethral resection. The primary endpoint was disease-free survival (DFS); the secondary endpoints included a complete response on cystoscopy at 3 mo (CR3mos), recurrence, progression, adverse events (AEs), and deaths from any cause. KEY FINDINGS AND LIMITATIONS: We randomised 501 participants (249 to BCG + MM and 252 to BCG alone), with pTa in 53%, pT1 in 47%, and concurrent CIS in 28%. The median follow-up was 48 mo. DFS was not superior for BCG + MM versus BCG alone (2-yr DFS rate: 75% vs 71%; hazard ratio 0.87, 95% confidence interval 0.65-1.16; p = 0.3). The numbers of events for BCG + MM versus BCG alone were as follows: 214 versus 210 (CR3mos), 79 versus 86 (recurrence), 28 versus 44 (progression), and 26 versus 23 (death). Those assigned BCG + MM had more instillations (4033 vs 3383) but fewer doses of BCG (total 2056 vs 3383; median nine vs 16) than BCG alone. Grade 3-5 AEs occurred in 43 assigned BCG + MM versus 37 assigned BCG alone. A higher number of participants assigned BCG + MM than those assigned BCG alone had ≥75% of their planned doses (78% vs 68%, p = 0.02). CONCLUSIONS AND CLINICAL IMPLICATIONS: BCG + MM was not proved superior to BCG alone, but required 39% fewer doses of BCG and fewer treatment discontinuations. These findings support consideration of BCG + MM as a pragmatic alternative to BCG alone, which could mitigate the global shortage of BCG.
Tateo V, Basile G, Giannatempo P
… +14 more, de Jong JJ, Proudfoot JA, Maiorano BA, Cigliola A, Mercinelli C, Davicioni E, Moschini M, Tremolada G, Rota S, Brembilla G, Colecchia M, De Cobelli F, Montorsi F, Necchi A
The PURE-01 trial evaluated three cycles of pembrolizumab 200 mg followed by radical cystectomy (RC) in patients with cT2-3b N0 M0 muscle-invasive bladder cancer (MIBC) ineligible for or refusing cisplatin. A total of 15...The PURE-01 trial evaluated three cycles of pembrolizumab 200 mg followed by radical cystectomy (RC) in patients with cT2-3b N0 M0 muscle-invasive bladder cancer (MIBC) ineligible for or refusing cisplatin. A total of 155 patients were treated. We report survival outcomes after median follow-up of >60 mo and associations with pathological response rates and biomarker levels. In the intention-to-treat population, the 5-yr event-free survival rate was 68% and the 5-yr overall survival (OS) rate was 77%. In the RC cohort, the 5-yr recurrence-free survival (RFS) rate was 77%. Pathological response categories were significantly associated with survival, with a 5-yr OS rate of ∼90% in the group achieving a complete or major response (p < 0.001). The 5-yr cumulative risk of recurrence was 19%, with three of 31 relapses occurring beyond 5 yr after RC. Eight patients refused RC and underwent transurethral resection; seven remain alive and disease-free. Transcriptome-wide profiling of pretreatment tissue was available for 102 patients. Stratification by genomic subtyping classifier showed that the claudin-low subtype (n = 14) had the highest 5-yr RFS rate, with a 5-yr OS rate of 93%. At long-term follow-up, PURE-01 demonstrates sustained survival outcomes and confirms the prognostic relevance of pathological response and molecular subtypes. These results support further investigation of single-agent immunotherapy as a potential de-escalation strategy in selected patients.
BACKGROUND AND OBJECTIVE: To report our multi-institutional outcomes with robotic intracorporeal ileal ureter replacement (RIUR). METHODS: We performed a retrospective review of patients who underwent RIUR at three insti...BACKGROUND AND OBJECTIVE: To report our multi-institutional outcomes with robotic intracorporeal ileal ureter replacement (RIUR). METHODS: We performed a retrospective review of patients who underwent RIUR at three institutions from April 2016 to June 2025. Surgical success was defined as the absence of flank pain and of ureteral obstruction on functional imaging and/or endoscopic evaluation, and freedom from operative intervention related to RIUR at ≥6-mo follow-up. KEY FINDINGS AND LIMITATIONS: Of 48 patients, 31 (64.6%) had unilateral and 17 (35.4%) had bilateral reconstruction. Twenty (41.7%) had a history of radiation. Median stricture length was 20 cm (interquartile range [IQR] 20-25). In 19 patients (39.6%), a concomitant abdominopelvic reconstruction was performed (9 bladder augmentations, 5 contralateral ureteral reconstructions, and 5 other procedures). Median operative time was 359 min (IQR 292-418), estimated blood loss was 100 ml (IQR 50-175), and length of stay was 5 d (IQR 4-7). There were nine (18.8%) major (Clavien grade ≥III) 30-d complications: five urinary anastomotic leaks, two intra-abdominal abscesses, one small bowel leak that required exploratory laparotomy, and one renal bleed requiring angioembolization. Thirty-six patients (75%) had ≥6-mo follow-up, which confirmed surgical success in 33/36 (91.7%) at median follow-up of 24 mo (IQR 14-35). All three failures were in the radiation subgroup, which had a significantly lower rate of surgical success (76.9% vs 100%; p = 0.031). CONCLUSIONS AND CLINICAL IMPLICATIONS: RIUR is an effective and durable treatment for patients with devastating ureteral injuries. However, the procedure is challenging and associated with a significant major complication rate. PATIENT SUMMARY: This study looked at a complex surgery in which a piece of intestine is used to rebuild the urinary tube that drains urine from the kidney to the bladder. Across three hospitals, the procedure worked well for the large majority of patients, and helped to restore function and relieve symptoms.
Kitamura H, Tsukamoto T, Kakehi Y
… +19 more, Mizusawa J, Shibata T, Sasaki K, Tanikawa T, Hashine K, Fujimoto K, Masumori N, Kobayashi T, Habuchi T, Kimura T, Sugimoto M, Takahashi A, Adachi H, Matsui Y, Hatakeyama S, Ito A, Eto M, Nishiyama H, Urologic Oncology Study Group of the Japan Clinical Oncology Group
BACKGROUND AND OBJECTIVE: We evaluated the noninferiority of active surveillance (AS) in comparison to intravesical bacillus Calmette-Guérin (BCG) in terms of recurrence and progression for patients with high-grade T1 (H...BACKGROUND AND OBJECTIVE: We evaluated the noninferiority of active surveillance (AS) in comparison to intravesical bacillus Calmette-Guérin (BCG) in terms of recurrence and progression for patients with high-grade T1 (HG T1) bladder cancer at initial transurethral resection of the bladder (TURB) and no residual tumor at second TURB. METHODS: After initial evaluation, participants diagnosed with HG T1 bladder cancer who had undergone complete eradication of visible tumors underwent a second TURB. Those with specimens showing T0 were randomized to either AS or to intravesical BCG for 8 wk without maintenance therapy. The primary endpoint was invasive relapse-free survival (iRFS). KEY FINDINGS AND LIMITATIONS: In total, 513 participants were enrolled in the initial evaluation. After second TURB, 263 participants were enrolled and randomized. AS was noninferior to BCG in terms of iRFS (hazard ratio 0.69, 90% confidence interval 0.44-1.08; p = 0.001). Rates of adverse events were 50% and 90% for any grade, and in 3.1% and 3.8% for grade ≥3 events in the AS and BCG arms, respectively. The protocol treatment in the control arm was not the current standard. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this highly selected patient population, AS was noninferior to eight-dose intravesical BCG induction therapy in terms of iRFS for T1 disease or deeper intravesical and/or extravesical recurrence. The safety profile of AS was better than that of BCG. These findings indicate that AS represents a potentially viable therapeutic strategy for selected patients with HG T1 bladder cancer for whom second TURB demonstrates the absence of residual disease.