Current Opinion in Urology最新文献

Purpose of review: Nonmuscle-invasive bladder cancer (NMIBC) patients with BCG-unresponsive disease have limited treatment options beyond radical cystectomy. With ongoing BCG shortages and the urgent need for bladder-preserving alternatives, this review examines the emerging role of oncolytic virus therapy as a novel intravesical treatment approach for this challenging patient population.

Recent findings: Multiple oncolytic viral platforms have entered clinical trials for NMIBC treatment, demonstrating promising efficacy and safety profiles. Cretostimogene grenadenorepvec has shown exceptional results in a phase 3 trial, achieving 74.5% complete response rates with durable responses exceeding 27 months in BCG-unresponsive carcinoma in situ. Combination therapy with pembrolizumab further enhanced efficacy, with a 57.1% complete response rate at 12 months and no progression to muscle-invasive disease. Other viral platforms, including herpes simplex, coxsackie, and measles viruses, have demonstrated preliminary antitumor activity with favorable safety profiles. These agents utilize three mechanisms of action: selective viral replication, direct oncolysis, and immune system activation.

Summary: Oncolytic virus therapy represents a paradigm shift toward an effective bladder-preserving treatment for BCG-unresponsive NMIBC. With phase 3 data supporting regulatory approval pathways, these therapies are poised to become new standards of care, offering hope for improved outcomes while avoiding radical surgery.

Purpose of review: Bacillus Calmette-Guérin (BCG) remains the standard of care for high-risk non-muscle-invasive bladder cancer (NMIBC), yet up to 40-50% of patients experience treatment failure, leaving limited alternatives to avoid radical cystectomy. This narrative review critically examines both traditional and emerging BCG-based strategies - including repeat induction and modern combination regimens - for patients with BCG-unresponsive NMIBC.

Recent findings: BCG monotherapy after BCG failure has shown limited effectiveness, with recent studies reporting 12-month disease-free survival (DFS) rates of 60-70%. Nonetheless, BCG continues to serve as an immunotherapeutic backbone in combination strategies. Chemo-immunotherapy regimens, particularly those using gemcitabine or mitomycin C, have achieved 1-year DFS rates of up to 80%. Combinations with cytokines and immunocytokines - such as interferon-α or nogapendekin alfa inbakicept-pmln (NAI) - have demonstrated DFS rates of 45-61%, and NAI has recently received FDA approval. Immune checkpoint inhibitors (e.g., pembrolizumab, durvalumab, atezolizumab) in combination with BCG have shown DFS rates ranging from 42 to 73% at 12 months. However, many studies are limited by small sample sizes and heterogeneous designs.

Summary: Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection.

Purpose of review: Nonmuscle invasive bladder cancer (NMIBC) represents approximately 75% of bladder cancer cases at diagnosis and poses a significant management challenge due to high recurrence rates and risk for progression. Conventional intravesical therapies face limitations including suboptimal drug delivery, mucosal exposure time and significant adverse events. This review provides a timely assessment of novel intravesical delivery systems developed to overcome these limitations and improve oncological outcomes for patients with NMIBC.

Recent findings: Several innovative delivery systems show promising results. Hyperthermic intravesical chemotherapy (HIVEC) demonstrates its efficacy in selected high-risk NMIBC. Intravesical drug-releasing systems (iDRS) like TAR-200 showed complete response rates up to 84% in BCG-unresponsive disease, while TAR-210 shows promise for FGFR-altered NMIBC. UGN-102, a reverse thermal gel containing mitomycin C, achieves 65-79% complete response rates in low-grade intermediate-risk NMIBC. Oncofid-P-B, combining paclitaxel with hyaluronic acid, demonstrates efficacy in BCG-unresponsive CIS.

Summary: Novel intravesical delivery systems show to enhance drug retention, improve tissue penetration, and potentially reduce adverse events. While traditional chemotherapy or BCG remain the gold-standard adjuvant treatments for NMIBC, these novel approaches offer promising alternatives for selected patients pending on ongoing clinical validation.

Purpose of review: Hyperthermic intravesical chemotherapy (HIVEC) and other device-assisted platforms are emerging bladder-sparing options after Bacillus Calmette-Guérin (BCG) failure in nonmuscle-invasive bladder cancer (NMIBC). This review integrates recent mechanistic, clinical and economic evidence to clarify their therapeutic position.

Recent findings: Prospective and real-world series in BCG-unresponsive disease report complete response rates of 40-60% for carcinoma in situ and 35-70% 12-24-month high-grade recurrence-free survival for papillary tumors. Radiofrequency-induced thermo-chemotherapy, recirculant chemohyperthermia and electromotive drug administration achieve comparable efficacy. Toxicity is usually grade 1-2 urinary urgency, frequency or dysuria, with serious events in fewer than 10% of patients. Health-economic modelling suggests HIVEC becomes cost-effective once high-grade recurrence-free survival exceeds 30% at 12 months.

Summary: Device-assisted hyperthermic chemotherapy combines biological plausibility, acceptable safety and favorable cost, positioning it as a potential option between BCG failure and radical cystectomy. Ongoing phase III trials will determine long-term oncological control, refine patient selection and optimize sequencing with systemic and intravesical agents.

Purpose of review: Treatment of Bacillus Calmette-Guérin (BCG)-refractory nonmuscle-invasive bladder cancer (NMIBC) is a significant clinical problem, with limited bladder-sparing strategies. The following review aims to show the recent advances in systemic immunotherapy that are transforming the treatment paradigm in patients with BCG-refractory NMIBC.

Recent findings: Developing evidence highlights the therapeutic success of immune checkpoint inhibitors, such as pembrolizumab and gene therapy, which received regulatory approval for high-risk BCG-refractory NMIBC. Combination regimens, with immunotherapy combined with intravesical therapy or chemotherapy, are under exploration to enhance treatment efficacy and bypass resistance. The identification of new molecular targets and the development of tailored strategies also depict the fast-paced evolution in this field.

Summary: Systemic immunotherapy is now of potential benefit in BCG-refractory NMIBC patients, providing viable bladder-sparing therapies. Our findings have significant implications for clinical practice and enable the transition to individualized, less invasive therapies. More work is required to optimize outcomes, expand therapeutic options, and improve quality of life in this challenging patient population.

Purpose of review: This review evaluates recent evidence on the utility of multiparametric MRI (mpMRI), prostate-specific membrane antigen (PSMA) PET, and their combined application for accurately delineating the intraprostatic gross tumour volume (GTV) in patients with primary localised and locally advanced prostate cancer. It further explores the impact of GTV-based dose escalation on treatment-related toxicity and clinical outcomes.

Recent findings: Recent studies suggest that combining PSMA-PET with mpMRI enhances lesion coverage of clinically significant, histopathologically verified intraprostatic tumours and yields higher interobserver agreement. However, this improved sensitivity is offset by reduced specificity, and it remains uncertain whether expanding the GTV to include additional PSMA-PET-defined regions impacts long-term treatment-related toxicity or improves oncological outcomes. Multiple phase I/II trials using PSMA-PET and mpMRI have reported acceptable acute and late toxicity profiles. Nevertheless, extensive data on long-term toxicity and disease outcomes following PSMA-PET-guided interventions remain limited, warranting further investigation to assess its impact.

Summary: The combination of mpMRI and PSMA-PET has been shown to improve coverage of dominant intraprostatic lesion and reduce interobserver variability. While GTVs derived from combined imaging modalities are typically larger than those based on mpMRI alone, hypofractionated focal boost treatments targeting PSMA-PET/mpMRI-defined GTVs have demonstrated acceptable acute toxicity profiles. More data are needed to determine the impact of PSMA-PET expanded GTVs on long-term clinical outcomes.

Purpose of review: This review synthesizes current evidence and recommendations for the use of lutetium-177 prostate-specific membrane antigen (LuPSMA) radioligand therapy across the spectrum of prostate cancer, focusing on its established use in metastatic castration-resistant prostate cancer (mCRPC), and evolving role in metastatic hormone-sensitive disease (mHSPC) and in neoadjuvant treatment of high-risk localized disease. We explore the potential for its use in biochemical recurrence (BCR) highlighting its limitations, and areas for future research.

Recent findings: LuPSMA has demonstrated oncological efficacy and tolerability over standard of care treatments in mCRPC, supported by landmark trials such as VISION, TheraP, and PSMAfore. In mHSPC, the UpFront PSMA and PSMAddition trials have demonstrated promising improvements in undetectable PSA rates and progression-free survival when LuPSMA was combined with standard therapies. Furthermore, the LuTectomy trial has shown that neoadjuvant LuPSMA prior to radical prostatectomy in high risk localised prostate cancer can deliver high but variable doses of targeted radiation to PSMA expressing cells, and is surgically safe and tolerated well.

Summary: LuPSMA radioligand therapy is a form of targeted therapy that has been shown to improve outcomes and quality of life in advanced disease with limited toxicity. While its use is well established in mCRPC, ongoing trials are exploring its efficacy in earlier disease stages and in combination with other therapies. Continued research and guideline development are essential to optimize LuPSMA's application across the prostate cancer disease spectrum, particularly in the BCR setting.

Purpose of review: The rising global incidence of prostate cancer has intensified both clinical and economic pressures to optimize radiotherapy (RT) delivery. Advances in imaging and fractionation - particularly magnetic resonance imaging (MR)-guided workflows and stereotactic body RT (SBRT) - aim to reduce treatment duration and minimize toxicity. This review explores these innovations and their potential inclusion into routine clinical practice.

Recent findings: MR-guided RT (MRgRT) planning and delivery offer superior soft tissue contrast and real-time motion tracking, enabling reduced target margins and improved sparing of adjacent normal tissues. Hypofractionated regimens (e.g., 60 Gy in 20 fractions) have become standard, while ultra-hypofractionated SBRT (up to 12 Gy per fraction over 2-5 sessions) is gaining traction due to MRgRT capabilities. Adaptive RT allows for daily modification of treatment plans, based on real-time imaging. Several trials, including MIRAGE and SCIMITAR, have demonstrated reductions in acute genitourinary and gastrointestinal toxicity with MR-guided SBRT. Ongoing clinical trials and the MOMENTUM registry aim to clarify long-term outcomes and contribute to the standardization of MRgRT workflows.

Summary: Based on available, preliminary evidence, MRgRT and adaptive SBRT are associated with a promising toxicity profiles. Nonetheless, further multicenter studies with extended follow-up are needed to validate outcomes and establish practice guidelines.

Purpose of review: This review explores challenges in managing biochemical recurrence (BCR) after radical prostatectomy and postoperative radiotherapy for prostate cancer (PCa) highlighting gaps in risk stratification, imaging, and emerging therapies, as well as advances in molecular imaging and personalized treatment.

Recent findings: Approximately half of PCa patients experience a second BCR after postoperative radiotherapy. Time to recurrence, PSA kinetics, adverse pathological features (ISUP 4-5, pT3-4, and positive surgical margins), alongside genetic profile, are key factors for risk stratification. Combination of androgen deprivation therapy (ADT) and novel androgen receptor pathway inhibitors (ARPIs) represents an established treatment choice. However, recent findings emphasize the growing role of prostate-specific membrane antigen (PSMA) PET in detecting recurrent disease and guide tailored strategies. Based on early phase II trials and retrospective studies, metastasis-directed therapy (MDT) has demonstrated promising efficacy in oligorecurrent PCa, although further validation is warranted.

Summary: BCR after radical prostatectomy and postoperative radiotherapy represents a challenge in PCa management. Risk stratification is key for guiding the addition of ARPIs to standard ADT. PSMA PET may further refine tailored strategies such as MDT, whose promising efficacy needs further exploration. Ongoing trials will clarify treatment sequencing and patient selection in the evolving paradigm of BCR management.

Purpose of review: We aimed to summarize the recent advancements in management of biochemical recurrence (BCR) after primary curative therapy for prostate cancer (PCa), and the role of advanced imaging technologies in guiding and improving treatment decisions.

Recent findings: Recent studies have reshaped the approach to managing BCR after primary treatment for PCa. A key shift is the preference for early salvage radiotherapy (sRT), which has proven to offer comparable or even superior outcomes to immediate adjuvant therapy when closely monitored for progression. PSA kinetics (PSA doubling time) continue to guide treatment decisions, together with the time to PSA rise, Gleason Grade of the original tumor, and PSMA-PET imaging at the time of recurrence. While PSMA-PET significantly enhances the precision of recurrence detection, its sensitivity for smaller pelvic lymph node metastases remains limited, underscoring the need for careful consideration of all factors together to develop a risk-based consulting for all individualized treatment plan integrating patient wishes and health.

Summary: Recent studies underscore the efficacy of early sRT in managing BCR, with PSA kinetics and ISUP score as a crucial factor in guiding treatment decisions. Furthermore, the integration of PSMA-PET imaging has improved the precision of recurrence detection, facilitating more tailored and effective treatment strategies for patients with BCR. We are finally entering the age of personalized, risk-based, patient-centred case delivery, where treatment of the primary tumor with curative intent is offered to patients with BCR.