RESUMO
INTRODUCTION: This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. METHODS: Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. RESULTS: A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. CONCLUSION: Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas , Excisão de Linfonodo , Terapia Neoadjuvante , Neoplasias Penianas , Humanos , Masculino , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/patologia , Neoplasias Penianas/mortalidade , Neoplasias Penianas/cirurgia , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Adulto , Estadiamento de Neoplasias , Metástase Linfática , Estudos Retrospectivos , Quimioterapia Adjuvante , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Recent progresses in the use of immune checkpoint inhibitor (ICI) have challenged the therapeutic standards in patients with muscle-invasive urothelial bladder carcinoma (MIBC). OBJECTIVE: To compare neoadjuvant pembrolizumab followed by radical cystectomy (RC) versus neoadjuvant chemotherapy (NAC) and RC or upfront RC, according to cisplatin eligibility. DESIGN, SETTING, AND PARTICIPANTS: We conducted two separate analyses for cisplatin-eligible and cisplatin-ineligible cT2-4N0M0 MIBC patients. We used a propensity score adjustment that relied on inverse probability of treatment-weighting (IPTW). INTERVENTION: Pembrolizumab within the PURE-01 trial, and NAC and RC or upfront RC from a high-volume tertiary care referral center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint in both analyses was event-free survival (EFS), defined as freedom from recurrence, and/or death from any cause indexed from the date of treatment initiation or RC. The secondary endpoints included EFS in propensity score-matched patients, pathologic response rate, and recurrence-free survival (RFS) after RC. RESULTS AND LIMITATIONS: A total of 458 patients who underwent RC, with or without NAC, at Moffitt Cancer Center between October 2005 and October 2020, and 146 patients enrolled in PURE-01 were analyzed. In cisplatin-ineligible patients, EFS was superior in those receiving pembrolizumab (p < 0.001). The estimated 3-yr EFS was 77.8% (95% confidence interval [CI]: 63.5-95.2) for pembrolizumab and RC, and 36.1% (95% CI: 28.6-45.5) for upfront RC. EFS remained superior in those receiving neoadjuvant ICI (NICI) following IPTW (p < 0.001). In cisplatin-eligible patients, EFS was superior in those receiving pembrolizumab and RC (p < 0.001). The estimated 3-yr EFS was 86.9% (95% CI: 80.9-93.3) for pembrolizumab and 63.5% (95% CI: 56.5-71.4) for NAC. EFS remained superior in those receiving NICI following IPTW (p < 0.001). Pathologic responses and RFS in pembrolizumab-treated patients were also superior to those in NAC-treated patients. Results are limited by the retrospective nature of the study. CONCLUSIONS: In the first ever reported comprehensive comparison of outcomes between neoadjuvant ICI and NAC, followed by RC, or upfront RC, we report increased responses and improved oncologic outcomes with neoadjuvant ICI in patients with MIBC. PATIENT SUMMARY: We compared the results obtained from the use of pembrolizumab and radical cystectomy with standard-of-care treatments in patients with bladder carcinoma infiltrating the muscle layer. We reported increased response and survival rates possibilities with the use of immunotherapy, anticipating the possibility to set new therapeutic standards in these patients, pending the results of ongoing randomized studies.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Cisplatino , Cistectomia , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Cisplatino/uso terapêutico , Masculino , Feminino , Cistectomia/métodos , Terapia Neoadjuvante/métodos , Idoso , Pessoa de Meia-Idade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Antineoplásicos Imunológicos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Optimal patient selection for neoadjuvant chemotherapy prior to surgical extirpation is limited by the inaccuracy of contemporary clinical staging methods in high-risk upper tract urothelial carcinoma (UTUC). OBJECTIVE: To investigate whether the detection of plasma circulating tumor DNA (ctDNA) can predict muscle-invasive (MI) and non-organ-confined (NOC) UTUC. DESIGN, SETTING, AND PARTICIPANTS: Plasma cell-free DNA was prospectively collected from chemotherapy-naïve, high-risk UTUC patients undergoing surgical extirpation and sequenced using a 152-gene panel and low-pass whole-genome sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To test for concordance, whole-exome sequencing was performed on matching tumor samples. The performance of ctDNA for predicting MI/NOC UTUC was summarized using the area under a receiver-operating curve, and a variant count threshold for predicting MI/NOC disease was determined by maximizing Youden's J statistic. Kaplan-Meier methods estimated survival, and Mantel-Cox log-rank testing assessed the association between preoperative ctDNA positivity and clinical outcomes. RESULTS AND LIMITATIONS: Of 30 patients enrolled prospectively, 14 were found to have MI/NOC UTUC. At least one ctDNA variant was detected from 21/30 (70%) patients, with 52% concordance with matching tumor samples. Detection of at least two panel-based molecular alterations yielded 71% sensitivity at 94% specificity to predict MI/NOC UTUC. Imposing this threshold in combination with a plasma copy number burden score of >6.5 increased sensitivity to 79% at 94% specificity. Furthermore, the presence of ctDNA was strongly prognostic for progression-free survival (PFS; 1-yr PFS 69% vs 100%, p < 0.001) and cancer-specific survival (CSS; 1-yr CSS 56% vs 100%, p = 0.016). CONCLUSIONS: The detection of plasma ctDNA prior to extirpative surgery was highly predictive of MI/NOC UTUC and strongly prognostic of PFS and CSS. Preoperative ctDNA demonstrates promise as a biomarker for selecting patients to undergo neoadjuvant chemotherapy prior to nephroureterectomy. PATIENT SUMMARY: Here, we show that DNA from upper tract urothelial tumors can be detected in the blood prior to surgical removal of the kidney or ureter. This circulating tumor DNA can be used to predict that upper tract urothelial carcinoma is invasive into the muscular lining of the urinary tract and may help identify those patients who could benefit from chemotherapy prior to surgery.
Assuntos
Carcinoma de Células de Transição , DNA Tumoral Circulante , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/diagnóstico , DNA Tumoral Circulante/genética , Estudos Retrospectivos , Prognóstico , Músculos/patologia , Neoplasias Ureterais/genética , Neoplasias Ureterais/cirurgiaRESUMO
OBJECTIVE: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101. PATIENTS AND METHODS: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis. RESULTS: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis. CONCLUSIONS: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors.
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Pélvicas , Ureter , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Neoplasias Ureterais/cirurgia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Constrição Patológica , Ureter/cirurgia , Ureter/patologia , Neoplasias Renais/patologia , Mitomicinas , Estudos RetrospectivosRESUMO
BACKGROUND: Despite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy. METHODS: A retrospective review was conducted in 805 patients with muscle invasive bladder cancer undergoing radical cystectomy with no perioperative chemotherapy, 761 with presurgical chemotherapy followed by radical cystectomy, and 134 radical cystectomy followed by adjuvant chemotherapy. Relevant clinicopathologic features were reviewed. Recurrence-free survival and Overall Survival probability estimates were calculated using the Kaplan-Meier method and compared using the Log-rank or Gehan-Breslow tests. The prognostic effects of presurgical chemotherapy and adjuvant chemotherapy regimens were evaluated by estimating hazard ratio and 95% confidence interval from an adjusted Cox proportional hazards model. Statistical tests were 2-sided, and significance was defined asâ¯P-value < 0.05. RESULTS: In this contemporary, real-world cohort, 5-yr RFS was found to be 65.6% in pT0, 59.1%in
Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Quimioterapia Adjuvante , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia Neoadjuvante/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS). PATIENTS AND METHODS: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) rate at month 6, defined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy. The null hypothesis specified a CR rate of 18% and alternative hypothesis of 40%. According to the Simon two-stage design, if ≤3/13 patients achieved CR during stage 1, the trial is stopped due to futility. RESULTS: Between March 8, 2017, and January 24, 2020, 17 patients were accrued whereas 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. Two of 17 (12%) achieved a CR at month 6, with duration of response of 10 and 18 months, respectively. A single grade 3 lipase elevation was attributed to durvalumab, and immune-related adverse events were observed in 7/17 (41%) patients. Only 1/17 patients had high programmed death-ligand 1 expression pretreatment. On RNA sequencing, complement activation genes were elevated posttreatment, along with enrichment of tumor-associated macrophage signature. CONCLUSIONS: Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6-month CR of 12%. Complement activation is a potential mechanism behind treatment resistance.
Assuntos
Carcinoma in Situ , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Vacina BCG/efeitos adversos , Bexiga Urinária/patologia , Anticorpos Monoclonais/efeitos adversos , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Invasividade Neoplásica , Administração Intravesical , Adjuvantes Imunológicos/uso terapêutico , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: UGN-101 can be used for chemoablation of low-grade upper tract urothelial carcinoma (UTUC). The gel can be administered via a retrograde route through a ureteral catheter or an antegrade route via a nephrostomy tube. OBJECTIVE: To report outcomes of UGN-101 by route of administration. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of 132 patients from 15 institutions who were treated with UGN-101 for low-grade UTUC via retrograde versus antegrade administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival outcomes are reported per patient. Treatment, complications, and recurrence outcomes are reported per renal unit. Statistical analysis was performed for primary endpoints of oncological response and ureteral stricture occurrence. RESULTS AND LIMITATIONS: A total of 136 renal units were evaluated, comprising 78 retrograde and 58 antegrade instillations. Median follow-up was 7.4 mo. There were 120 cases (91%) of biopsy-proven low-grade UTUC. Tumors were in the renal pelvis alone in 89 cases (65%), in the ureter alone in 12 cases (9%), and in both in 35 cases (26%). Seventy-six patients (56%) had residual disease before UGN-101 treatment. Chemoablation with UGN-101 was used in 50/78 (64%) retrograde cases and 26/58 (45%) antegrade cases. A complete response according to inspection and cytology was achieved in 31 (48%) retrograde and 30 (60%) antegrade renal units (p = 0.1). Clavien grade 3 ureteral stricture occurred in 21 retrograde cases (32%) and only six (12%) antegrade cases (p < 0.01). Limitations include treatment bias, as patients in the antegrade group were more likely to undergo endoscopic mechanical ablation before UGN-101 instillation. CONCLUSIONS: These preliminary results show a significantly lower rate of stricture occurrence with antegrade administration of UGN-101, with no apparent impact on oncological efficacy. PATIENT SUMMARY: We compared results for two different delivery routes for the drug UGN-101 for treatment of cancer in the upper urinary tract. For the antegrade route, a tube is inserted through the skin into the kidney. For the retrograde route, a catheter is inserted past the bladder into the upper urinary tract. Our results show a lower rate of narrowing of the ureter (the tube draining urine from the kidney into the bladder) using the antegrade route, with no difference in cancer control.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Constrição Patológica , Neoplasias Renais/patologia , Neoplasias Ureterais/patologia , Mitomicina , Pelve Renal/patologiaRESUMO
PURPOSE: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101. MATERIAL AND METHODS: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease. RESULTS: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17). CONCLUSION: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Estudos Retrospectivos , Ureteroscopia/métodos , Néfrons , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/cirurgia , Neoplasias Ureterais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
BACKGROUND: Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option. OBJECTIVE: To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease. DESIGN, SETTING, AND PARTICIPANTS: Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis. RESULTS AND LIMITATIONS: UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias. CONCLUSIONS: Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population. PATIENT SUMMARY: We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Insuficiência Renal Crônica , Rim Único , Neoplasias da Bexiga Urinária , Humanos , Mitomicina , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Estudos Retrospectivos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Recidiva Local de Neoplasia , Rim/patologia , Insuficiência Renal Crônica/complicações , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVE: Guideline recommendations disagree on template boundaries for pelvic lymph node dissection (PLND) in conventional urothelial carcinoma. Less is known about PLND in variant histology. We aimed to analyze the role of LND in plasmacytoid urothelial carcinoma (PUC). METHODS: A retrospective review of patients with cTanyNanyM0 PUC who underwent radical cystectomy (RC) with PLND was performed from 2012 to 2022. Lymph node count (LNC) was a surrogate for extent of lymph node dissection and dichotomized based on maximally selected rank statistics. Multivariable cox hazard regression analysis (MVA) for overall survival (OS) corrected for age, perioperative chemotherapy, soft tissue margin status, and stage ≥pT3 and/or pN+ was performed. Disease free survival (DFS) and OS were estimated using Kaplan-Meier (KM) analysis. RESULTS: Sixty-seven patients with median age of 71, who were 79.1% male were included. Neoadjuvant and adjuvant chemotherapy were administered in 61.2% and 19.4% of patients, respectively. At RC, 70.1% were ≥pT3. Median LNC was 22 (IQR 14-27) with 43.3% of patients being pN+. Calculated optimal-LNC cut point for DFS and OS was 19. Grouping by optimal (≥20) vs. suboptimal-LNC (<20), no significant clinicodemographic differences were found. Optimal-LNC provided improved DFS (Pâ¯=â¯0.05) and OS (Pâ¯=â¯0.02). Optimal-LNC (HR 0.47, 0.24-0.93 CI 95%, Pâ¯=â¯0.03) and negative soft tissue margin (HR 0.38, 0.19-0.76 CI 95%, Pâ¯=â¯0.01) was associated with improved OS on MVA. Receipt of perioperative chemotherapy did not improve OS (Pâ¯=â¯0.46). CONCLUSION: In PUC, complete surgical extirpation achieving negative soft tissue margins and removing ≥20 lymph should be prioritized if operative intervention is pursued.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Masculino , Feminino , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Margens de Excisão , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Estudos Retrospectivos , CistectomiaRESUMO
Precision medicine has transformed the way urothelial carcinoma is managed. However, current practices are limited by the availability of tissue samples for genomic profiling and the spatial and temporal molecular heterogeneity observed in many studies. Among rapidly advancing genomic sequencing technologies, non-invasive liquid biopsy has emerged as a promising diagnostic tool to reproduce tumour genomics, and has shown potential to be integrated in several aspects of clinical care. In urothelial carcinoma, liquid biopsies such as plasma circulating tumour DNA (ctDNA) and urinary tumour DNA (utDNA) have been investigated as a surrogates for tumour biopsies and might bridge many shortfalls currently faced by clinicians. Both ctDNA and utDNA seem really promising in urothelial carcinoma diagnosis, staging and prognosis, response to therapy monitoring, detection of minimal residual disease and surveillance. The use of liquid biopsies in patients with urothelial carcinoma could further advance precision medicine in this population, facilitating personalized patient monitoring through non-invasive assays.
Assuntos
Carcinoma de Células de Transição , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , DNA de Neoplasias/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética , DNA Tumoral Circulante/genética , Biomarcadores Tumorais/genéticaRESUMO
PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Penianas , Masculino , Humanos , Virilha , Neoplasias Penianas/patologia , Canal Inguinal , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo , Carcinoma de Células Escamosas/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Estadiamento de NeoplasiasRESUMO
PURPOSE: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. RESULTS: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). CONCLUSIONS: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Mitomicina , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Constrição Patológica , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/cirurgia , Quimioterapia AdjuvanteRESUMO
BACKGROUND: UGN-101 is a novel delivery system for intracavitary treatment of upper tract urothelial cancer (UTUC). UGN-101 was approved based on a pivotal trial for small volume residual low-grade UTUC. Our aim was to report our experience with UGN-101 in a more heterogenous and real-world setting. METHODS: We performed a retrospective review of all UGN-101 cases from 15 institutions with a focus on practice patterns, efficacy, and adverse effects. We include UGN-101 utilization in both the chemoablative and adjuvant setting. RESULTS: There were a total 136 renal units treated from 132 patients. The majority of cases were biopsy proven low-grade UTUC. Practice patterns varied considerably - the most common administration technique was antegrade instillation via a percutaneous nephrostomy. When utilized in the adjuvant setting, 69% of patients were disease free at the time of their first endoscopic evaluation, while in the chemoablative setting, 37% were endoscopically clear on the first evaluation (P < 0.001). Complete response was higher in patients with smaller tumor size prior to UGN-101 induction; low volume (<1 cm) residual disease was associated with a 70% complete response, similar to disease free rate at first endoscopic evaluation when UGN-101 was used in the adjuvant setting. The use of maintenance doses of UGN-101 was reported in 27% of cases. The overall incidence of new onset, clinically significant ureteral stenosis was 23%. CONCLUSIONS: This study represents the largest review of patients treated with UGN-101 and can serve as a basis of ongoing hypotheses regarding treatment with UGN-101 for UTUC.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Neoplasias Renais/patologia , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Mitomicina/uso terapêutico , Urotélio/patologia , Adjuvantes Imunológicos/uso terapêutico , Neoplasias Ureterais/patologiaRESUMO
OBJECTIVES: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS: Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS: Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.
Assuntos
Carcinoma de Células de Transição , Nefrostomia Percutânea , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Mitomicina , Estudos Retrospectivos , Constrição Patológica , Neoplasias Ureterais/tratamento farmacológicoRESUMO
PURPOSE: Chylous ascites (CA) is an uncommon complication that occurs from traumatic disruption of lymphatic channels after retroperitoneal surgery. The purpose of this study was to generate an evidence-based management strategy for CA by reviewing the current literature and available treatment modalities. MATERIALS AND METHODS: A MEDLINE® literature review was performed for "chylous ascites." Individual patient data were extracted from case series and reports to create an efficacy analysis. Treatment modality, drain output, time to escalation of care and time to resolution were recorded. The efficacy analysis was utilized to generate a data-driven treatment algorithm. RESULTS: The literature review yielded 1,953 articles, from which 146 studies contributed data for 523 patients. The efficacy analysis included 245 patients, 168 (69%) of whom were managed successfully with conservative management (CM), at a median time to resolution of 11 days. Forty-eight patients underwent lymphangiography±embolization after CM, with a success rate of 85%. Thirty-one (12%) patients underwent surgical exploration. When treating CA, the patients who underwent stepwise management with CM followed by lymphangiography if CM failed experienced a resolution rate of 96.7%. An evidence-based treatment algorithm was created to guide treatment selection and duration of therapy before escalating to additional forms of therapy. CONCLUSIONS: In this report, we describe the largest conglomeration of iatrogenic CA cases from a literature review (523 cases) and efficacy analysis (245 cases), and created the first evidence-based treatment algorithm for this condition. Treatment success is substantial when using a stepwise combination of CM followed by lymphangiography±embolization.
Assuntos
Ascite Quilosa , Embolização Terapêutica , Algoritmos , Ascite Quilosa/diagnóstico , Ascite Quilosa/etiologia , Ascite Quilosa/terapia , Embolização Terapêutica/efeitos adversos , Humanos , Linfografia/efeitos adversos , Espaço RetroperitonealRESUMO
OBJECTIVES: To compare ureteroenteric stricture rates after radical cystectomy in patients who undergo an intracorporeal urinary diversion versus other surgical approaches. METHODS: We retrospectively reviewed health records of all patients who underwent cystectomy with urinary diversion at Mayo Clinic Hospital (Phoenix, AZ, USA) from 1 January 2007 through 1 January 2018. Ureteroenteric stricture was identified by surveillance imaging. Patients were stratified by surgical approach: open radical cystectomy, robot-assisted radical cystectomy with extracorporeal urinary diversion and robot-assisted radical cystectomy-intracorporeal urinary diversion. A Cox proportional hazards model was fitted that included independent predictors of stricture development. RESULTS: Of the 573 cystectomies assessed, 236 (41.2%) were carried out robotically. In the robot-assisted radical cystectomy cohort, 39 patients (16.5%) underwent intracorporeal urinary diversion. The median follow-up period was 55, 70 and 71 months for the open radical cystectomy, robot-assisted radical cystectomy-extracorporeal urinary diversion and robot-assisted radical cystectomy-intracorporeal urinary diversion groups, respectively. Subgroup stricture rates were as follows: open radical cystectomy, 8.0%; robot-assisted radical cystectomy-extracorporeal urinary diversion, 9.6%; and robot-assisted radical cystectomy-intracorporeal urinary diversion, 2.6% (P = 0.33). The median time to stricture was 5 months (interquartile range 3.3-11.5 months). In the bivariable analysis, factors that were associated with the development of ureteroenteric stricture were postoperative urinary leak (hazard ratio 3.177, 95% confidence interval 1.129-8.935; P = 0.03) and body mass index (hazard ratio 1.078, 95% confidence interval 1.027-1.132; P = 0.002). On multivariable logistic regression analysis, intracorporeal urinary diversion approach was not associated with the development of ureteroenteric stricture (hazard ratio 0.272, 95% confidence interval 0.036-2.066; P = 0.21). CONCLUSIONS: Ureteroenteric stricture is a complication that typically occurs within the first postoperative year. Although our results did not support major differences in outcomes between intracorporeal urinary diversion and extracorporeal urinary diversion, the small sample size did not exclude the possibility of a type 2 statistical error.
Assuntos
Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Derivação Urinária , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Cistectomia/efeitos adversos , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversosRESUMO
OBJECTIVE: To predict overall survival, cancer, and metastasis specific survival in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: All nonmetastatic UTUC patients who underwent RNU with a curative intent at 1 institution between December 1998 and January 2017 were included. Detailed data were collected. End points for this study included OS, CCS, and MFS. Univariate and multivariate analysis were conducted. Log Rank tests and Kaplan-Meier curves were generated. Backward elimination and boot strapping was used to identify the most parsimonious model with the smallest number of variables in order to predict the outcomes of interest. A separate second institution data base was used for external validation. RESULTS: There were 218 patients in the development cohort. Mean follow-up was 42 months (±39.6). There was 99 (45.4%) deaths, 28 (12.8%) cancer related deaths, 72 (33%) recurrences, and 54 (24.8%) metastases. The c-index for our model was 0.71 for OS, 0.72 for MFS and 0.74 for CSS. The nomograms did not show significant deviation from actual observations using our calibration plots. We divided the patient into 3 different groups (low, intermediate and high risk) based on their final total score for each outcome and compared them. On external validation our accuracy was 78.4%, 71.4%, and 75.3% for OS, CSS, and MFS survival respectively. CONCLUSION: We designed a predictive model for survival outcomes following RNU in UTUC. This model uses simple, readily available data for patients without the need for expensive or additional testing.