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INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting. METHODS: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method. RESULTS: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQRâ¯=â¯61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI ORâ¯=â¯4.1 (95% CI 1.2-13.6; Pâ¯=â¯0.024) and pathological nodal involvement ORâ¯=â¯4.5 (95% CI 1.3-15.7; Pâ¯=â¯0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001). CONCLUSION: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR.
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Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Terapia Neoadjuvante/métodos , Nefroureterectomia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fatores de RiscoRESUMO
BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.
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Neoplasias Testiculares/epidemiologia , Adulto , Humanos , Masculino , Provedores de Redes de Segurança , Fatores SocioeconômicosRESUMO
INTRODUCTION: There is controversy regarding the benefit of a grossly complete transurethral resection of bladder tumor (TURBT) for muscle-invasive bladder cancer (MIBC) in patients prior to neoadjuvant chemotherapy (NAC). Advocates for this approach suggest a higher response rate to NAC, while others suggest this can increase the surgical risk for no clear benefit. METHODS: We retrospectively reviewed our institutional radical cystectomy (RC) database from 2011 to 2018 for patients who received an adequate course of cisplatin-based NAC for nonmetastatic MIBC. Univariable and multivariable logistic regression analyses were performed to identify factors associated with complete response [ypT0] or no residual muscle invasive bladder cancer [ypT < 2] following NAC based on clinicopathologic characteristics and grossly complete or incomplete TURBT. RESULTS: A total of 167 patients received NAC followed by RC for MIBC during the study period and 100 patients were included in the analysis due to known status of the completeness of TURBT-of these 49 patients underwent complete resection while 51 patients underwent incomplete resection prior to NAC. There were no significant differences in baseline clinicopathologic characteristics between patients who had complete vs. incomplete TURBT. At the time of RC, the overall ypT0 rate was 24% (nâ¯=â¯24), while the overall rate of ypT < 2 was 45%. On logistic regression, there was no association between completeness of TURBT and ypT0 or ypT < 2. Age, histology, and organ-confined disease were not significantly associated with response to NAC. Only smoking status (current or prior history) was negatively associated with ypT0 on univariable and multivariable analysis (odds ratioâ¯=â¯0.36, 95% confidence interval: [0.14-0.91], Pâ¯=â¯0.031). CONCLUSION: We found no association between response to cisplatin-based NAC and completeness of TURBT in a cohort of MIBC patients. The study is limited by its retrospective nature and lack of ability to predict response to NAC based on TURBT tissue evaluation.
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Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento , Uretra , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. METHODS: We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. RESULTS: 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (Pâ¯=â¯0.055), CSS (Pâ¯=â¯0.152), and RFS (Pâ¯=â¯0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). CONCLUSIONS: Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.
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Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/patologia , Idoso , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Resultado do Tratamento , Neoplasias Ureterais/cirurgiaRESUMO
OBJECTIVES: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC. METHODS: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CNâ¯+â¯IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes. RESULTS: Of 391 patients, 221 (56.5%) received CNâ¯+â¯IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CNâ¯+â¯IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN. CONCLUSION: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.
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Carcinoma de Células Renais/terapia , Procedimentos Cirúrgicos de Citorredução , Imunoterapia , Neoplasias Renais/terapia , Nefrectomia/métodos , Idoso , Carcinoma de Células Renais/mortalidade , Estudos de Coortes , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma. The appropriate duration for ICI treatment is not clear, however. Analyses of landmark trials reveal that some patients exhibit sustained durable responses to ICIs even after treatment discontinuation, resulting in prolonged treatment-free intervals that can mitigate potential toxicities and the considerable financial burden associated with treatment. Adaptive approaches with PD1 monotherapy and combination immunotherapy tailored to tumor response are ongoing. More efforts will be needed to clarify the ideal ICI dosing regimen to maximize oncological benefit while minimizing treatment-related adverse effects and costs. PATIENT SUMMARY: We reviewed considerations surrounding treatment strategies when using immunotherapy to treat patients with kidney cancer. It is clear that some patients can experience prolonged cancer control when discontinuing immunotherapy. However, individualized approaches will be necessary to strike a balance between optimizing patient outcomes and reducing unnecessary side effects and cost.
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Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Duração da Terapia , Imunoterapia/métodos , Neoplasias Renais/patologia , Neoplasias Renais/terapia , HumanosRESUMO
OBJECTIVE: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). METHODS: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. RESULTS: Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. CONCLUSION: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.
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Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Terapia Neoadjuvante/métodos , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Estudos de Viabilidade , Feminino , Humanos , Ipilimumab/uso terapêutico , Rim/patologia , Rim/cirurgia , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
There are several treatment approaches for stage II germ cell tumors (GCTs), and a thorough understanding of the staging classification and histologic differences in tumor biology and therapeutic responsiveness is critical to determine an effective, multimodal management strategy that involves urologists, medical oncologists, and radiation oncologists. This article discusses contemporary management strategies for stage II GCTs, including chemotherapy, radiotherapy, retroperitoneal lymph node dissection (RPLND), and surveillance. Patient selection, histology, and extent of lymphadenopathy drive management, and, as both treatment and detection strategies continue to emerge and be refined, the management of patients with stage II GCT continues to evolve.
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Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Intervalo Livre de Doença , Custos de Cuidados de Saúde , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Qualidade de VidaRESUMO
PURPOSE OF REVIEW: The recent approval of immune checkpoint inhibitors (ICI) revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, the role of cytoreductive nephrectomy is not well defined in this setting. Here, we review the contemporary role and timing of cytoreductive nephrectomy for advanced RCC in the era of immunotherapy. RECENT FINDINGS: Evidence concerning combination systemic therapy and cytoreductive nephrectomy in the multimodal management of mRCC is primarily limited to studies conducted in the targeted therapy era. The oncologic role of cytoreductive nephrectomy in the setting of ICI remains largely undefined and is supported primarily by case reports. Nonetheless, patient selection for cytoreductive nephrectomy is paramount, and appropriate candidacy in the ICI era will likely be refined as increasing evidence emerges. Until then, a cautious balance between perceived oncologic benefit and risks of intervention must be exercised. Several trials are ongoing to help shed light on patient selection, technical feasibility, and optimal timing of cytoreductive nephrectomy in the immunotherapy era. SUMMARY: Although the role and timing for cytoreductive nephrectomy remain to be further elucidated in the immunotherapy era, patient selection remains critical for treatment planning. Further studies are urgently needed to better define the role of cytoreductive nephrectomy in this setting.
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Antineoplásicos Imunológicos/administração & dosagem , Carcinoma de Células Renais/terapia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Renais/terapia , Nefrectomia , Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/tendências , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/tendências , Inibidores de Proteínas Quinases/administração & dosagemRESUMO
BACKGROUND: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.
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Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER , Adulto JovemRESUMO
PURPOSE OF REVIEW: Understanding the molecular basis underlying testicular germ cell tumors (TGCTs) may help improve patient outcomes, particularly for patients with poorer risk or chemoresistant disease. Here, we review the major contemporary advances in elucidating TGCT genetics by discussing patterns of TGCT inheritance, recent genomic and transcriptomic discoveries in TGCT, and the role of genetics in predicting therapeutic resistance and in guiding treatment. RECENT FINDINGS: In the absence of a major high-penetrance TGCT susceptibility gene, inheritance is likely driven by a complex polygenic model with considerable variation. The most common genomic alterations found in TGCTs include gains in chromosome 12p and mutations in KIT, KRAS, and NRAS, particularly in seminomas. Sensitivity to cisplatin-based chemotherapy likely relies on intact TP53, reciprocal loss of heterozygosity, and high mitochondrial priming. Targetable mutations are uncommon in TGCTs, however, posing a challenge for the development of effective personalized therapies. Consistent with the characteristically low tumor mutational burden, immune checkpoint inhibitors do not appear to be effective for most TGCTs. SUMMARY: Refinements in next-generation sequencing techniques over the last few years have enabled considerable advances in elucidating the genomic, transcriptomic, and epigenetic landscape of TGCTs. Future efforts focused on developing novel treatment modalities are needed.
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Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Biomarcadores Tumorais/análise , Marcadores Genéticos/genética , Genoma , Humanos , Padrões de Herança/genética , Masculino , Mutação , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Testiculares/diagnóstico , TranscriptomaRESUMO
INTRODUCTION: The systemic options for managing metastatic renal cell carcinoma (mRCC) have expanded considerably over the past decade. Initially limited to cytokines, clinicians may now choose from several classes of targeted therapies and, most recently, immune checkpoint inhibitors. Areas covered: In this review, we discuss the role and timing of cytoreductive nephrectomy (CN) and its evolution starting with cytokines, and then alongside the emergence of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Patient selection remains the most critical determinant in offering CN, and the anticipated survival benefits of CN must be weighed against the surgical morbidity and potential delay to receipt of systemic therapies. Expert opinion: Proper patient selection is key for decision-making in mRCC. Prospective data is urgently needed to define the role of CN in the contemporary immunotherapy era, with greater personalization of prognostic models.
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Carcinoma de Células Renais/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Renais/terapia , Carcinoma de Células Renais/patologia , Citocinas/metabolismo , Tomada de Decisões , Humanos , Imunoterapia/métodos , Neoplasias Renais/patologia , Terapia de Alvo Molecular , Nefrectomia/métodos , Seleção de Pacientes , PrognósticoRESUMO
PURPOSE OF REVIEW: To evaluate contemporary sex-specific differences in upper tract urothelial carcinoma (UTUC) by reviewing diagnostic considerations, clinicopathologic features, oncologic outcomes, environmental exposures, and regional variation in UTUC by sex. RECENT FINDINGS: Although some contemporary studies implicate sex-based differences in UTUC, the literature concerning the effect of sex on clinicopathologic features and oncologic outcomes in UTUC reveals mixed findings. Factors accounting for the time to diagnosis in UTUC seem to differ between men and women. The epidemiology and outcomes of UTUC are largely influenced by geographic variation in the disease, which may be due to differences in exposure to environmental risk factors. Sex-based variations and potential differences in disease biology remain to be elucidated. SUMMARY: A global consensus on the effect of sex on clinicopathologic characteristics and oncologic outcomes in UTUC has not been established definitively. Review of this topic does, however, shed light on important considerations given differences in the time to diagnosis, risk factors, and regional variation by sex. Further studies evaluating genetic, anatomic, physiologic, and socioeconomic differences between men and women with UTUC may provide further insight into understanding the effect of sex in UTUC.
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Carcinoma de Células de Transição/fisiopatologia , Neoplasias Urológicas/fisiopatologia , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Neoplasias Urológicas/diagnóstico , UrotélioRESUMO
INTRODUCTION: The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials. AREAS COVERED: We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents often used in combination with LHRH agonists. We review these candidates in the specific clinical niche in which they might find utility. EXPERT OPINION: Of all candidate compounds being evaluated in clinical trials, very few will receive FDA approval. Few, if any of the investigational agents discussed here will be used routinely in clinical practice for treating prostate cancer. Recognizing the reasons for the failure of agents to advance to later stage trials is important. Furthermore, a thorough understanding of the mechanisms underlying prostate cancer pathogenesis, including various points in the HGPA and parallel pathways, will help identify potentially actionable targets.
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Antineoplásicos Hormonais/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/farmacologia , Animais , Antineoplásicos Hormonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/administração & dosagem , Drogas em Investigação/farmacologia , Humanos , Masculino , Neoplasias da Próstata/patologiaRESUMO
INTRODUCTION: Partial cystectomy use has historically been limited by stringent selection criteria. We compared outcomes following partial cystectomy at our institution with those in other contemporary series. Also, we specifically characterized outcomes in patients with tumors in bladder locations traditionally considered unamenable to partial cystectomy. METHODS: Patients who underwent partial cystectomy for primary bladder cancer from 1990 to 2012 were identified from our database. Clinical and pathological data were reviewed. Survival analyses were performed using Kaplan-Meier methods. Cox regression was done to identify factors associated with survival and recurrence. RESULTS: A total of 55 patients were included in analysis. Five-year overall, disease specific and recurrence-free survival was 70.3%, 77.0% and 39.4%, respectively. When controlling for clinical and pathological covariates, lymphovascular invasion predicted decreased recurrence-free survival (HR 10.6, p = 0.025). Perioperative morbidity and mortality rates were 4% and 5%, respectively. In 8 patients (15%) trigone tumors required ureteral reimplantation. Two of the 8 patients (25%) experienced complications, including hydronephrosis and bladder neck contracture, which were treated conservatively. Cancer recurred in 2 of the 8 patients (25%) and both were treated successfully. None of the 8 patients died of bladder cancer. CONCLUSIONS: Patients treated with partial cystectomy for primary bladder cancer had satisfactory cancer control and favorable perioperative morbidity consistent with other contemporary reports. Patients with tumors in the bladder trigone, historically considered poor candidates for partial cystectomy, also had good oncologic outcomes without significant complications related to reimplantation. Our data further support partial cystectomy in select patients with bladder cancer.
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Renal cell carcinoma is the most common cancer of the kidneys that is primarily treated with surgery, including removal of part or all the involved kidney depending on size and tumor, complexity, and patient characteristics. Partial nephrectomy historically was restricted to cases of solitary kidney or bilateral tumors. It was then started for masses smaller than 4 cm and currently is even studied and justified in tumors smaller than 7 cm if surgically feasible. Although partial nephrectomy preserves kidney tissue and, therefore, delays or prevents the new onset of CKD and ESRD, radical nephrectomy is still overused even for the small tumors. Studies have shown that although this practice is driven by an easier complete removal of the kidney especially in the era of minimally invasive surgery, partial nephrectomy is successful in curing cancer and achieving excellent cancer-specific survival in addition to its benefits on cardiovascular health. Nowadays interest in preserving healthy kidney tissue is increasing to the level of studying the impact of larger volume removed around the kidney and the histopathology of that non-neoplastic tissue to predict kidney function behavior postoperatively.
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Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Néfrons , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/prevenção & controle , Insuficiência Renal Crônica/prevenção & controle , Medição de Risco , Carga TumoralRESUMO
PURPOSE: We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. MATERIALS AND METHODS: Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. RESULTS: A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy and 14 undergoing cryoablation. Median tumor size was 2.2 cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs surveillance (-9.2 vs -0.5 ml/minute/1.73 m(2)) and for radical vs partial nephrectomy (-9.2 vs -1.9 ml/minute/1.73 m(2)) (p=0.001). No other groups differed significantly. On Kaplan-Meier analysis patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs those treated with partial nephrectomy (p=0.029), surveillance (p=0.007) and cryoablation (p=0.019). No other groups differed significantly. On multivariate analysis radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs surveillance 30.6, p=0.001). Neither partial nephrectomy (p=0.985) nor cryoablation (p=0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. CONCLUSIONS: Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses.
Assuntos
Neoplasias Renais/terapia , Nefrectomia/métodos , Conduta Expectante , Idoso , Criocirurgia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Carga TumoralRESUMO
OBJECTIVE: To determine whether heterogeneity of tumor grade affects the response to Bacillus Calmette-Guérin (BCG) treatment for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Patients with Ta or T1 NMBIC receiving a 6-week induction course of intravesical BCG therapy after transurethral resection were divided according to the tumor grade. Clinical and pathological variables were compared. Advanced intervention-free survival (AIFS), defined as duration of freedom from advanced intervention (including non-BCG intravesical agents or cystectomy) or metastasis, was plotted using Kaplan-Meier methods. The effect of grade on survival duration was assessed by multivariate Cox proportional hazards modeling. RESULTS: One hundred and fifty-three patients were identified: 17 with mixed low- and high-grade (MG) and 136 with pure high-grade (PHG) NMIBC. Demographic and additional pathologic variables were comparable between groups (p > 0.05). Five-year AIFS was 88.2% for MG patients, compared to 48.5% for PHG patients (p = 0.030 by log-rank test). On multivariate analysis, PHG was an independent risk factor for worse AIFS (HR 4.4, 95% CI 1.1-18.4, p = 0.040). Among patients failing to respond to primary BCG induction, who underwent a secondary induction of BCG with interferon, MG patients had better response than PHG patients (100 vs. 26.3%, p = 0.035). CONCLUSIONS: Mixed low- and high-grade NMIBC exhibits a significantly better response profile to intravesical BCG therapy compared to PHG NMIBC. The implications of these results are that less aggressive treatment strategies for this unique cancer entity may be needed and that there is a benefit to the reporting of tumor heterogeneity in transurethral resection of bladder tumor specimens.