PURPOSE OF REVIEW: This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. RECENT FINDINGS: Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. SUMMARY: Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.

• MeSH
• Cystectomy * methods   MeSH
• Immunotherapy methods   MeSH
• Neoplasm Invasiveness * MeSH
• Organ Sparing Treatments * methods   MeSH
• Humans MeSH
• Urinary Bladder surgery   pathology   MeSH
• Urinary Bladder Neoplasms * therapy   pathology   surgery   MeSH
• Patient Selection MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cieľ: Cieľom práce bolo vyhodnotiť výsledky liečby svalovinu infiltrujúcich nádorov močového mechúra radikálnou TURB s následnou adjuvantnou chemoterapiou, rádioterapiou alebo ich kombináciou so zachovaním funkčného močového mechúra. Klinický súbor a metódy: Retrospektívne sme vyhodnotili pacientov so svalovinou infiltrujúcich urotelových nádorov, ktorí boli liečení na urologickej klinike v Martine v rokoch 2005–2016 radikálnou TURB a následnou adjuvantnou liečbou. Ak histologické vyšetrenie potvrdilo infiltratívny urotelový karcinóm pT2a-pT2b, všetkým pacientom sme urobili re-TURB. Do analýzy boli zaradení len pacienti, ktorí mali po re-TURB negatívne histologické vyšetrenie (pT0), primárny solitárny nádor mal veľkosť menej ako 3 cm, nemali prítomnú ureterohydronefrózu, nádor neprerastal cez stenu močového mechúra a nemali difúzny CIS. Následne boli pacienti liečení adjuvantnou chemoterapiou, rádioterapiou alebo ich kombináciou. Štatisticky sme vyhodnotili základnú charakteristiku pacientov, spôsob adjuvantnej liečby, výskyt recidív a celkové prežívanie. Výsledky: Súbor 14 pacientov vo veku 54–69 rokov (priemer 61 r.) tvorilo 7 žien a 7 mužov. Všetci mali po radikálnej TUR-B potvrdený infiltratívny urotelový karcinóm pT2a-pT2b, G2-G3. Po re-TURB nemal žiadny pacient nález reziduálneho nádoru (pT0), jeden pacient mal na CT zväčšené obturá- torové LU do 3 cm. Adjuvantnú chemoterapiu ako monoterapiu absolvovalo 6 (42%) pacientov, 7 (50%) absolvovalo konkomitantnú chemorádioterapiu a 1(8%) pacientka odmietla akúkoľvek liečbu. Lokálnu recidívu nádoru s infiltráciou svaloviny nemal za sledované obdobie žiadny pacient, jeden pacient (8%) mal po dvoch rokoch chirurgicky odstránené obturátorové LU (potvrdené metastázy), 3(21%) pacienti mali recidívu neinvazívneho high- -grade urotelového karcinómu pT1,G3. 13(92%) pacienti prežívajú 1–11 rokov (medián 6 rokov), žiadny pacient neexitoval na progresiu ochorenia, 1(8%) pacient exitoval na akútny IM. Záver: Z našej limitovanej štúdie vyplýva, že u dobre selektovaných pacientov s infiltratívnymi urotelovými nádormi močového mechúra (pT0 po re-TURB) môžeme po trimodálnej liečbe dosiahnuť kompletnú remisiu ochorenia s minimálnym rizikom lokálnej ako aj systémovej progresie a dlhodobým beznádorovým prežívaním. Pri tejto liečebnej stratégii je nevyhnutná multidisciplinárna spolupráca urológov, radiačných onkológov a klinických onkológov ako aj úzka spolupráca od pacientov, ktorí vyžadujú dlhoročné pravidelné cystoskopické ako aj CT/MR kontroly pre riziko lokálnej alebo systémovej recidívy. KĽÚČOVÉ SLOVÁ Infiltratívne nádory močového mechúra,

Objectives: The aim of this study was to evaluate treatment outcomes of muscle-invasive bladder cancers treated with radical TURB followed by adjuvant chemotherapy, radiotherapy, or their combination in order to preserve functional bladder. Material and methods: We retrospectively evaluated patients with muscle-invasive urothelial tumors who were treated at the Department of Urology in Martin from 2005–2016 by radical TURB followed by adjuvant therapy. If histological examination confirmed invasive urothelial carcinoma (pT2a-pT2b) all such patients underwent re-TURB. In the analysis were included only patients who had negative histology (pT0) after re-TURB, the primary solitary tumor was ≤3 cm in size, ureterohydronephrosis was not present, not the presence of diffuse CIS and there was no tumor invaded outside the bladder wall. Thereafter, patients were treated with adjuvant chemotherapy, radiotherapy or their combination. Statistically, we evaluated baseline characteristics of the patients, adjuvant therapy, recurrence rate and overall survival. Results: The cohort of 14 patients aged 54–69 years (mean 61 years) consisted of 7 women and 7 men. All of the patients after radical TUR-B had confirmed invasive urothelial carcinoma pT2a-pT2b, G2-G3 After re-TURB no patient had residual tumor from the base (pT0), one patient had CT verified enlargement of obturator LN up to 3 cm. Adjuvant chemotherapy as a monotherapy underwent 6 (42%) patients, 7 (50%) underwent concomitant chemoradiotherapy and 1 (8%) patient refused any treatment. Local recurrence of muscle-invasive bladder tumor was not present in none of the patients, 1 (8%) patient surgically removed obturator LN (confirmed metastasis) after two years, 3 (21%) patients had a recurrence of a non-invasive high-grade urothelial carcinoma pT1, G3. 13 (92%) patients are surviving 1–11 years (median 6 years), no patient has died because of disease progression, 1 (8%) patient died due to MI. Conclusion: The results of our limited study suggest, that in well- selected patients with muscle invasive transitional cell bladder cancers (pT0 after re-TURB) after trimodal therapy we can achieve complete response with minimal risk of local or systemic progression and long-term cancer specific-free survival. It requires multidisciplinary collaboration of urologist, radiation oncologist and medical oncologist as well as close cooperation of patients who require regular long-term cystoscopic and CT / MR surveillance because of a risk of local or systemic recurrence.

• MeSH
• Chemoradiotherapy methods   MeSH
• Organ Sparing Treatments * methods   MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   surgery   radiotherapy   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH

PURPOSE OF REVIEW: The treatment of bacillus Calmette-Guérin (BCG) unresponsive disease remains a challenge for urooncologists. The search for effective conservative treatments is ongoing and several new agents have been recently tested for this purpose. The aim of this manuscript was to review the last developments in this interesting field. RECENT FINDINGS: The advent of systemic immunotherapy in the nonmuscle invasive setting promise to revolutionize the paradigm of treatment of BCG unresponsive disease. The preliminary results of the Keynote-057 trial (3 months complete response of 41% in carcinoma-in-situ patients) have led to the rapid approval of pembrolizumab from the Food and Drug Administration. Interesting results have been reported for gene therapies such as those with CG0700 and Adstiladrin, nonreplicating adenovirus able to increase the 'in situ' antitumor activity. However, larger prospective trials with longer follow-up are needed to confirm the initial findings. SUMMARY: In summary, early radical cystectomy remains the standard treatment for BCG unresponsive patients. However, in case of patients unfit for or refusing radical cystectomy, the bladder-sparing options are continuously increasing. Although BCG-reinduction (with or without interferon) and traditional intravesical chemotherapy may represent the past, the present and the future are characterized by device-assisted therapies, systemic immunotherapy, and gene therapy.

• MeSH
• Administration, Intravesical MeSH
• BCG Vaccine therapeutic use   MeSH
• Genetic Therapy * MeSH
• Immunotherapy * MeSH
• Neoplasm Invasiveness MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Urinary Bladder Neoplasms therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND AND OBJECTIVE: There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. METHODS: A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. KEY FINDINGS AND LIMITATIONS: There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.

• MeSH
• Adjuvants, Immunologic therapeutic use   MeSH
• BCG Vaccine * therapeutic use   MeSH
• Cystectomy MeSH
• Neoplasm Invasiveness * MeSH
• Organ Sparing Treatments * MeSH
• Humans MeSH
• Non-Muscle Invasive Bladder Neoplasms MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   MeSH
• Patient Selection * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Practice Guideline MeSH

• MeSH
• Cisplatin therapeutic use   MeSH
• Gemcitabine * MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   MeSH
• Neoadjuvant Therapy MeSH
• Nivolumab therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Muscles MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH

• MeSH
• Adjuvants, Immunologic MeSH
• BCG Vaccine immunology   MeSH
• Cytotoxicity, Immunologic MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Tumor Microenvironment MeSH
• Urinary Bladder Neoplasms immunology   therapy   MeSH
• Salvage Therapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH

PURPOSE: To demonstrate an efficient method for training and validation of a knowledge-based planning (KBP) system as a radiation therapy clinical trial plan quality-control system. METHODS AND MATERIALS: We analyzed 86 patients with stage IB through IVA cervical cancer treated with intensity modulated radiation therapy at 2 institutions according to the standards of the INTERTECC (International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer, National Clinical Trials Network identifier: 01554397) protocol. The protocol used a planning target volume and 2 primary organs at risk: pelvic bone marrow (PBM) and bowel. Secondary organs at risk were rectum and bladder. Initial unfiltered dose-volume histogram (DVH) estimation models were trained using all 86 plans. Refined training sets were created by removing sub-optimal plans from the unfiltered sample, and DVH estimation models… and DVH estimation models were constructed by identifying 30 of 86 plans emphasizing PBM sparing (comparing protocol-specified dosimetric cutpoints V10 (percentage volume of PBM receiving at least 10 Gy dose) and V20 (percentage volume of PBM receiving at least 20 Gy dose) with unfiltered predictions) and another 30 of 86 plans emphasizing bowel sparing (comparing V40 (absolute volume of bowel receiving at least 40 Gy dose) and V45 (absolute volume of bowel receiving at least 45 Gy dose), 9 in common with the PBM set). To obtain deliverable KBP plans, refined models must inform patient-specific optimization objectives and/or priorities (an auto-planning "routine"). Four candidate routines emphasizing different tradeoffs were composed, and a script was developed to automatically re-plan multiple patients with each routine. After selection of the routine that best met protocol objectives in the 51-patient training sample (KBPFINAL), protocol-specific DVH metrics and normal tissue complication probability were compared for original versus KBPFINAL plans across the 35-patient validation set. Paired t tests were used to test differences between planning sets. RESULTS: KBPFINAL plans outperformed manual planning across the validation set in all protocol-specific DVH cutpoints. The mean normal tissue complication probability for gastrointestinal toxicity was lower for KBPFINAL versus validation-set plans (48.7% vs 53.8%, P<.001). Similarly, the estimated mean white blood cell count nadir was higher (2.77 vs 2.49 k/mL, P<.001) with KBPFINAL plans, indicating lowered probability of hematologic toxicity. CONCLUSIONS: This work demonstrates that a KBP system can be efficiently trained and refined for use in radiation therapy clinical trials with minimal effort. This patient-specific plan quality control resulted in improvements on protocol-specific dosimetric endpoints.

• MeSH
• Clinical Trials as Topic standards   MeSH
• Bone Marrow MeSH
• Organs at Risk * MeSH
• Organ Sparing Treatments methods   standards   MeSH
• Humans MeSH
• Urinary Bladder MeSH
• Uterine Cervical Neoplasms pathology   radiotherapy   MeSH
• Pelvic Bones MeSH
• Radiotherapy Planning, Computer-Assisted methods   standards   MeSH
• Radiotherapy, Intensity-Modulated methods   standards   MeSH
• Rectum MeSH
• Quality Control * MeSH
• Intestines MeSH
• Tumor Burden MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Validation Study MeSH

Invazivní karcinom močového měchýře (MIBC) je tradičně léčen neoadjuvantní chemoterapií (NAC) a radikální cystektomií (RACE). Přestože trimodální terapie (TMT), zahrnující maximální transuretrální resekci (TUR) a chemoradioterapii (CHRT), přináší srovnatelné výsledky, není dosud považována za standardní léčbu. Tato práce analyzuje výsledky recentních studií a doporučení týkajících se TMT v léčbě MIBC. Retrospektivní analýzy naznačují, že TMT dosahuje podobného přežití bez metastáz (MFS) a přežití bez nemoci (DFS) jako NAC s RACE. Neexistence přímého srovnání TMT a NAC s RACE však omezuje implementaci TMT jako standardní metody léčby. I přesto nová doporučení uznávají TMT jako rovnocennou alternativu pro pacienty s omezenou způsobilostí k NAC nebo RACE nebo preferující zachování močového měchýře. Nové strategie zahrnující imunoterapii ukazují potenciál ke zlepšení výsledků. Závěrem lze říci, že TMT představuje účinný orgán záchovný postup u vybraných pacientů s MIBC, avšak volba léčebné strategie vyžaduje individuální přístup a multi­disciplinární spolupráci.

Muscle-invasive bladder cancer (MIBC) has traditionally been treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RACE). Although trimodal therapy (TMT), involving maximal transurethral resection (TUR) and chemoradiotherapy (CRT), yields comparable results, it is not yet considered standard treatment. This paper analyses the results of recent studies and recommendations concerning TMT in the treatment of MIBC. Retrospective analyses suggest that TMT achieves metastasis-free survival (MFS) and disease-free survival (DFS) rates similar to those obtained by NAC with RACE. However, the lack of direct comparison of TMT and NAC plus RACE limits the implementation of TMT as a standard treatment method. Nevertheless, new recommendations recognise TMT as an equally valid alternative for patients with restricted eligibility for NAC or RACE, or for those who prefer bladder preservation. Novel strategies including immunotherapy show potential for improved outcomes. In conclusion, TMT is an effective organ-preserving procedure in selected patients with MIBC; however, the choice of treatment strategy requires a tailored approach and multidisciplinary collaboration.

• MeSH
• Chemoradiotherapy methods   MeSH
• Neoplasm Invasiveness MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   radiotherapy   MeSH
• Radiotherapy methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

PURPOSE OF REVIEW: Trimodal therapy (TMT) is considered the most effective bladder-sparing approach for muscle-invasive urothelial carcinoma of the bladder (MIBC) and an alternative to radical cystectomy. The purpose of this article was to review and summarize the current knowledge on the equivalence of TMT and radical cystectomy based on the recent literature. RECENT FINDINGS: TMT consists of a maximal transuretral resection of the bladder, followed by a concurrent radiotherapy and chemotherapy, limiting salvage radical cystectomy to nonresponder tumors or muscle-invasive recurrence. In large population studies, less than 6% of the patients with nonmetastatic MIBC receive a chemoradiation therapy and this rate is stable. A growing body of evidence exists that TMT provides good oncologic outcomes with low morbidity when compared with radical cystectomy. TMT requires, however, a close follow-up because of the high risk of local recurrence and salvage radical cystectomy in up to 30% of the patients. Salvage radical cystectomy can be performed with adequate results but does not offer the same opportunity of reconstruction and functional outcomes than primary radical cystectomy. SUMMARY: Although radical cystectomy is still the treatment of reference for most of the patients with localized MIBC, TMT represents a reasonable alternative in highly selected patients. Any firm conclusion on the equivalence or superiority of one treatment to the other is still limited by the lack of randomized controlled trials and the heterogeneity of the available literature. Future studies and multidisciplinary approach are mandatory to optimize the patient selection and regimen of TMT.

• MeSH
• Chemoradiotherapy, Adjuvant * adverse effects   MeSH
• Time Factors MeSH
• Cystectomy adverse effects   methods   MeSH
• Neoplasm Invasiveness MeSH
• Carcinoma pathology   therapy   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Urinary Bladder Neoplasms pathology   therapy   MeSH
• Risk Factors MeSH
• Neoplasm Staging MeSH
• Urothelium * pathology   MeSH
• Patient Selection MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Zatímco systémová léčba se v kombinaci s operačním výkonem implementovala do léčebné praxe na základě studií potvrzujících klinický benefit velice úspěšně, míra využití radioterapie jako alternativy cystektomie u vysoce selektovaných pacientů se v různých zemích liší. Měchýř zachovávající léčba je vhodná zejména pro pacienty neschopné či neochotné podstoupit radikální chirurgický výkon. Pro dobré léčebné výsledky je naprosto zásadní provedení radikální transuretrální resekce tumoru močového měchýře (TURBT) a podání konkomitantní chemoterapie, která zlepšuje přežití v pěti letech až o 13 %. V takovém případě je možno dosáhnout u dlouhodobě přežívajících pacientů až v 80 % zachování močového měchýře, přičemž závažná pozdní toxicita třetího a vyššího stupně (dle stupnice RTOG) nepřesahuje 10 %. Naopak při indikaci konzervativního přístupu u nemocných s tumory neumožňujícími TURBT, lokálně pokročilým onemocněním (T3-4), hydronefrózou či kontraindikací cisplatiny lze očekávat spíše pouze paliativní efekt léčby.

While systemic treatment in combination with surgery has very successfully been implemented into therapeutic practice based on studies demonstrating a clinical benefit, the utilization rate of radiotherapy as an alternative to cystectomy in highly selected patients varies in different countries. Bladder preservation therapy is particularly suitable for patients unable or unwilling to undergo radical surgery. In order to obtain good therapeutic results, it is essential to perform radical transurethral resection of the bladder tumour (TURBT) and administer concomitant chemotherapy that improves 5-year survival by as much as 13 %. Under these circumstances, it is possible to achieve preservation of a functional bladder in up to 80 % of long-term surviving patients, with severe late toxicity of grade 3 and higher (according to the RTOG scale) not exceeding 10 %. Conversely, when a conservative approach is indicated in patients with tumours not allowing TURBT, locally advanced disease (T3-4), and hydronephrosis, or when cisplatin is contraindicated, only a palliative effect of the treatment may rather be expected.

• MeSH
• Radiation Dosage MeSH
• Gastrointestinal Tract radiation effects   MeSH
• Carcinoma * therapy   MeSH
• Organ Sparing Treatments * methods   MeSH
• Humans MeSH
• Urinary Bladder radiation effects   MeSH
• Urinary Bladder Diseases * therapy   MeSH
• Non-Randomized Controlled Trials as Topic MeSH
• Radiotherapy methods   adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH