RESUMO
Background Despite definitive local therapy, patients with high-risk prostate cancer have a significant risk for local and distant failure. To date, no systemic therapy given prior to surgery has been shown to improve outcomes. The phosphatidilinositol 3-kinase/AKT/mTOR pathway is commonly dysregulated in men with prostate cancer. We sought to determine the clinical efficacy and safety of the mTOR/TORC1 inhibitor everolimus in men with high-risk prostate cancer undergoing radical prostatectomy. Methods This is a randomized phase II study of everolimus at two different doses (5 and 10 mg daily) given orally for 8 weeks before radical prostatectomy in men with high-risk prostate cancer. The primary endpoint was the pathologic response (histologic P0, margin status, extraprostatic extension) and surgical outcomes. Secondary endpoints included changes in serum PSA level and treatment effects on levels of expression of mTOR, p4EBP1, pS6 and pAKT. Results Seventeen patients were enrolled: nine at 10 mg dose and eight at 5 mg dose. No pathologic complete responses were observed and the majority of patients (88%) had an increase in their PSA values leading to this study being terminated early due to lack of clinical efficacy. Treatment-related adverse events were similar to those previously reported with the use of everolimus in other solid tumors and no additional surgical complications were observed. A significant decrease in the expression of p4EBP1 was noted in prostatectomy samples following treatment. Conclusions Neoadjuvant everolimus given at 5 mg or 10 mg daily for 8 weeks prior to radical prostatectomy did not impact pathologic responses and surgical outcomes of patients with high-risk prostate cancer. Trial registration NCT00526591 .
Assuntos
Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias da Próstata/patologia , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer. MATERIALS AND METHODS: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density. Nonparametric testing was performed to compare the median Genomic Prostate Score™ and the likelihood of favorable pathology findings between quartiles of disease volume. RESULTS: We identified 112 (37.8%) and 184 men (62.2%) at NCCN very low and low risk, respectively. Median scores did not differ significantly between disease volume quartiles (all p >0.05). However, the median likelihood of favorable pathology findings statistically differed between volume quartiles (all <0.05). Seven of the 105 men (6.3%) with very low risk disease were reclassified at low risk and 13 of 181 (7.2%) with low risk disease were reclassified at intermediate risk. Genomic disease reclassification did not depend on biopsy tumor volume. CONCLUSIONS: In patients with NCCN very low and low risk prostate cancer genomic scores did not demonstrate meaningfully significant differences by volume based on clinically established cutoff points. Moreover, genomic scores identified and reclassified men with higher risk disease despite generally acceptable surveillance characteristics in this group according to grade and volume. This suggests that in patients at low risk the tumor biological potential measured by genomics rather than by volume should inform decisions on active surveillance candidacy.
Assuntos
Genômica , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Conduta ExpectanteRESUMO
PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.
Assuntos
Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Conduta Expectante , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Medição de Risco , Taxa de SobrevidaRESUMO
Objective: To evaluate the long-term functional and oncologic outcomes after robotic partial nephrectomy (RAPN) and radical nephrectomy (RARN). Materials and Methods: A retrospective review was performed on 1816 patients who underwent RAPN and RARN at our institution between January 2006 and January 2018. Patients with long-term follow-ups of at least 5 years were selected. Exclusion criteria included patients with a previous history of partial or radical nephrectomy, known genetic mutations, and whose procedures were performed for benign indications. Statistical analysis was performed with results as presented. Results: A total of 769 and 142 patients who underwent RAPN and RARN, respectively, met our inclusion criteria. The duration of follow-up was similar after the two procedures with a median of â¼100 months. The 5- and 10-year chronic kidney disease (CKD) upstaging-free survivals were 74.5% and 65.9% after RAPN and 53% and 46.4% after RARN, respectively. Older age was identified as a potential predictor for CKD progression after RARN, whereas older age, higher body mass index, baseline renal function, and ischemia time were shown to predict CKD progression after RAPN. Renal cell carcinoma-related mortality rates for RAPN and RARN were equally 1.1%. No statistically significant differences were identified in the local recurrence, metastatic, and disease-specific survival between the two procedures. Conclusion: Compared with RARN, RAPN conferred a better CKD progression-free survival. Several factors were identified as potential predictors for clinically significant CKD progression both in the early and late postoperative phase. Long-term oncologic outcomes between the two procedures remained similarly favorable.
Assuntos
Neoplasias Renais , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Estudos Retrospectivos , Seguimentos , Resultado do Tratamento , Idoso , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , AdultoRESUMO
PURPOSE: For select men with low risk prostate cancer active surveillance is more often being considered a management strategy. In a multicenter retrospective study we evaluated the actuarial rates and predictors of remaining on active surveillance, the incidence of cancer progression and the pathological findings of delayed radical prostatectomy. MATERIALS AND METHODS: A cohort of 262 men from 4 institutions met the inclusion criteria of age 75 years or younger, prostate specific antigen 10 ng/ml or less, clinical stage T1-T2a, biopsy Gleason sum 6 or less, 3 or less positive cores at diagnostic biopsy, repeat biopsy before active surveillance and no treatment for 6 months following the repeat biopsy. Active surveillance started on the date of the second biopsy. Actuarial rates of remaining on active surveillance were calculated and univariate Cox regression was used to assess predictors of discontinuing active surveillance. RESULTS: With a median followup of 29 months 43 patients ultimately received active treatment. The 2 and 5-year probabilities of remaining on active surveillance were 91% and 75%, respectively. Patients with cancer on the second biopsy (HR 2.23, 95% CI 1.23-4.06, p = 0.007) and a higher number of cancerous cores from the 2 biopsies combined (p = 0.002) were more likely to undergo treatment. Age, prostate specific antigen, clinical stage, prostate volume and number of total biopsy cores sampled were not predictive of outcome. Skeletal metastases developed in 1 patient 38 months after starting active surveillance. Of the 43 patients undergoing delayed treatment 41 (95%) are without disease progression at a median of 23 months following treatment. CONCLUSIONS: With a median followup of 29 months active surveillance for select patients appears to be safe and associated with a low risk of systemic progression. Cancer at restaging biopsy and a higher total number of cancerous cores are associated with a lower likelihood of remaining on active surveillance. A restaging biopsy should be strongly considered to finalize eligibility for active surveillance.
Assuntos
Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
UNLABELLED: What's known on the subject? and What does the study add? Little has been published related to transponders per se, but a number of studies relating to prostate biopsy-related infections and the increased incidence of quinolone-resistant Escherichia coli have been published. The study alerts the practising urologist to the risk of quinolone-resistant E. coli in the setting of transrectally placed transponders. Furthermore, it proposes an antibiotic regimen that should reduce this risk. OBJECTIVE: To report our series of early infectious complications after placement of Calypso(®) transponders (Calypso Medical, Seattle, WA, USA) into the prostate. PATIENTS AND METHODS: Between February 2008 and October 2010, 50 consecutive patients underwent placement of Calypso(®) transponders into the prostate. Patients were administered ciprofloxacin 500 mg every 12 h, starting the night before the procedure and for 2 days after the procedure. Data were collected via chart review, and complications were classified according to the Clavien classification system. RESULTS: Of the 50 patients undergoing the procedure, five (10%) developed infectious complications, and three (6%) developed a grade II complication with a UTI requiring antibiotic therapy. One patient (2%) developed a grade IIIb complication with an epidural abscess and osteomyelitis of the lumbar vertebrae requiring open debridement and a lumbar fusion. One patient (2%) developed a prostatic abscess with methicillin-resistant Staphylococcus aureus and subsequently died of an unrelated lower GI bleed. In 4/50 patients (8%), a culture confirmed the responsible bacteria, of which three cases were quinolone-resistant Escherichia coli. CONCLUSION: As with prostate biopsy, the emergence of quinolone-resistant E. coli remains a challenging infectious complication with transrectal prostate procedures. We propose an alternative strategy of double antibiotic coverage with one dose of oral ciprofloxacin 500 mg and gentamicin 80 mg i.m. before this procedure.
Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Radioterapia/instrumentação , Estudos RetrospectivosRESUMO
The prostate-specific antigen (PSA) era has increased the rates of prostate cancer detection and treatment, while reducing the risk of death from prostate cancer in the US. Image-guided prostate biopsy techniques have led to stage migration and the detection and treatment of lower risk prostate cancers. Improved techniques with laterally directed biopsy, office-based saturation biopsy, and transperineal biopsy under anesthesia have increased the detection rates of smaller volume tumors. Improved detection of ever-smaller tumors assists the clinician in determining what treatment is most appropriate for the patient, including the use of active surveillance and focal therapy. Furthermore, the detection of small volume, high grade cancers may widen the latency interval in which a clinically significant tumor may be detectable and curable.
Assuntos
Biópsia por Agulha/métodos , Biópsia por Agulha/normas , Próstata/patologia , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos Ambulatórios , Humanos , MasculinoRESUMO
OBJECTIVE: To identify differences in neuroinflammatory gene expression in individuals with chronic orchialgia (CO) compared to asymptomatic controls. METHODS: Vas deferens, spermatic cord fascia, blood, and urine were collected from 9 men with CO at time of microscopic spermatic cord denervation and 7 asymptomatic controls at time of vasectomy. RNA was isolated and analyzed with the NanoString Human Neuroinflammation panel. Data were normalized, gene expression fold changes and enriched pathways relative to asymptomatic controls were determined. Gene expression was considered significantly different if there was a >2-fold change and P-value <.05 relative to controls. RESULTS: Mean patient age was 51 years and median symptom duration 12 months. There were 26 genes with significantly differential expression in vas deferens. cFos, a marker of nociceptive pain, had the greatest difference (30.2-fold change, P <.000001). Enriched pathways in vas deferens included nerve function, matrix remodeling, and innate immune responses. In fascia, cFos also had the greatest differential expression (38-fold, P = .000002), followed by S100A12 (11-fold, inducer of innate immune response). Enriched pathways in fascia included nerve function and inflammation. In blood, there were no differentially expressed genes, and in urine there were 95 differentially expressed genes. CONCLUSION: Men with CO have a diverse set of neuroinflammatory genes with differential expression in tissue and urine relative to healthy controls. These findings confirm pathologic changes in tissue targeted by denervation surgery, and suggest molecular changes in neuropathic pain that could lead to biomarker identification and novel treatment.
Assuntos
Cordão Espermático , Doenças Testiculares , Denervação , Expressão Gênica , Humanos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Dor/cirurgia , Cordão Espermático/cirurgia , Doenças Testiculares/genética , Doenças Testiculares/cirurgiaRESUMO
OBJECTIVE: To examine relationships between neighborhood socioeconomic disadvantage and outcomes following radical cystectomy (RC). MATERIALS AND METHODS: A retrospective single institution study of consecutive RCs performed for bladder cancer between 2011 and 2019. Major complications, mortality and survival outcomes were compared using Cochran-Armitage or Kruskal-Wallis tests. Cox proportional hazards models were used for time-to-event analyses. RESULTS: A total of 906 patients were included in analysis. Overall 90-day mortality was 2.98% (27/906). Ninety-day mortality rates observed in the least (first) and most (fourth) disadvantaged ADI quartiles were 0% (0/115) and 6.5% (12/185), respectively. Patients from the fourth quartile demonstrated worse overall survival and recurrence free survival than those in the first quartile. ADI quartile was positively associated with muscle invasive (Pâ¯=â¯.0006) and node positive (Pâ¯=â¯.042) disease. ADI percentile was an independent predictor for 90-day mortality (adjusted OR: 1.022, CI: 1.004-1.04, Pâ¯=â¯.015). CONCLUSION: Higher rates of mortality and worse oncologic outcomes were observed for patients residing in the most disadvantaged quartile. ADI was associated with higher likelihood of 90-day mortality and may therefore be useful in patient counseling, risk stratification, and post-discharge management.
Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Assistência ao Convalescente , Cistectomia/efeitos adversos , Humanos , Alta do Paciente , Estudos Retrospectivos , Fatores Socioeconômicos , Resultado do TratamentoRESUMO
OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (Pâ¯=â¯0.82) or overall survival (Pâ¯=â¯0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.
Assuntos
Cistectomia , Segunda Neoplasia Primária/cirurgia , Neoplasias da Próstata/radioterapia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Cistectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
INTRODUCTION: We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. METHODS: A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. RESULTS: IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. CONCLUSIONS: In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.
RESUMO
OBJECTIVE: To compare pathologic and survival outcomes between primary muscle invasive (pMIBC) and secondary muscle invasive (sMIBC) bladder cancer patients who were treated with or without cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We reviewed cT2-T4/N0 MIBC patients at our institution between 2010-2019. pMIBC was defined as presenting with > cT2 disease on initial or restaging TURBT with no prior history of bladder cancer. sMIBC was defined as prior history of NMIBC that was treated with at least one induction course of BCG that progressed to MIBC. Outcomes analyzed included pathologic downstaging rates defined as
Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/uso terapêutico , Cisplatino/uso terapêutico , Cistectomia/métodos , Músculos/patologia , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has diverse clinical phenotypes and its etiology is multifactorial. Studies to date of gene expression in humans have been limited to small numbers of target genes. NanoString can simultaneously measure hundreds of genes. We wished to study gene expression in blood and urine of CP/CPPS patients compared to controls for neuroinflammatory genes and characterize the results by patient phenotype. METHODS: Blood and urine were collected from 10 men with CP/CPPS and 7 asymptomatic controls. RNA was isolated from urine pellets using Qiagen RNeasy kits. Whole blood was collected and RNA isolated. 100 ng of RNA was used for gene expression analysis with the 770-gene NanoString Human Neuroinflammation gene panel. Data was imported into Rosalind (OnRamp Bioinformatics) for normalization, calculation of fold-changes and P values, and identification of enriched pathways. Gene expression was considered significantly different if there was a greater than 1.5× change compared to controls and corrected P was <0.05. RESULTS: Mean patient age was 42.2 years, median symptom duration was 15.5 months, median UPOINT domains was 3 and mean total National Institute of Health-Chronic Prostatitis Symptom Index Score was 28.8. In blood, there were 5 genes with significantly different expression to controls, the largest differences found in FOS1 (neuropathic pain control), PROS1 (blood clotting) and DDX58 (antiviral innate immunity). Gene set analysis showed differences in inflammation, angiogenesis and cytokine signaling. In urine there were 48 genes with significantly different expression including SLAMF8 (lymphocyte activation) and LAIR1 (inhibits B and T cell function). Gene set analysis showed differences in carbohydrate metabolism, neurons and neurotransmission, adaptive immunity and inflammatory signaling. Subgroup analysis by UPOINT domain showed unique gene expression in the Organ Specific and Neurologic/Systemic domains in both blood and urine for neurogenic pain and cytokine signaling associated genes. CONCLUSIONS: Men with CP/CPPS have a diverse set of neuroinflammatory genes with differential expression compared to controls. Clinical phenotypes have distinct patterns of gene expression. These findings could lead to novel biomarker development, emphasize the importance of multimodal therapy targeting diverse pathways and further validate the biologic basic of clinical phenotyping.
RESUMO
STUDY TYPE: Diagnostic (exploratory cohort). LEVEL OF EVIDENCE: 2b. OBJECTIVE: To develop a nomogram to predict the probability that the pathological Gleason sum (GS) will be higher than that indicated by the biopsy, suggesting a higher risk for the patient presumed to be at low risk, as a substantial proportion of patients with low and intermediate grade on biopsy are upgraded on interpretation of the radical prostatectomy (RP) specimens, but a similar clarification of accurate Gleason scoring is not available in patients with no surgical histology. PATIENTS AND METHODS: The study included 1017 patients who had RP after biopsy showing GS 6 and 7 (3 + 4) from 2000 to 2007. Nomogram predictor variables included age, race, digital rectal examination, prostate-specific antigen (PSA) level, number of cores taken, number of positive cores, maximum percentage cancer in any core, number of previous biopsies, prostate volume, clinical stage, high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, inflammation and perineural invasion. We calculated the nomogram-predicted probability in each patient. The area under the receiver operating characteristic curve was calculated as a measure of discrimination, and the calibration was assessed graphically. RESULTS: The mean age of the patients was 60 years, the mean PSA level 6.62 ng/mL; 336 patients were upgraded (33%), 623 remained the same (61.3%) and 58 were downgraded (5.7%). A nomogram for predicting the possibility of upgrading was constructed that had a concordance index of 0.68. The nomogram was well calibrated. CONCLUSIONS: Our nomogram for predicting upgrading provides important additional information for deciding on treatment to both the urologist and the patient with low- and intermediate-grade prostate cancer. It might prove useful when the possibility of a more aggressive Gleason variant can change the management, and is especially meaningful when management options other than surgery are selected based on the inability to recognize the true pathological actual GS.
Assuntos
Nomogramas , Próstata/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Biópsia , Exame Retal Digital , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Análise de RegressãoRESUMO
OBJECTIVES: Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious. MATERIALS AND METHODS: Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx. RESULTS: Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%. CONCLUSIONS: Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.
Assuntos
Neoplasias da Próstata/radioterapia , Qualidade de Vida , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
OBJECTIVE: To determine the relationship between urologic oncology fellowship training (UOFT) and diagnostic yield of prostate biopsy. METHODS: Retrospective review was conducted of patients who underwent prostate biopsy across the Cleveland Clinic between 2000 and 2018. Biopsies done by urologists with and without UOFT were detailed via descriptive statistics and appropriate (chi-square, Student t, Wilcoxon rank-sum) tests. Multivariate logistic regression was used to examine the association between UOFT and positive prostate biopsy, adjusting for relevant covariates. RESULTS: A total of 11,241 biopsies by 129 urologists had complete information available for review. Sixteen urologists (12.4%) had UOFT; 113 either completed a different fellowship or no fellowship. Those with UOFT were more likely to use MRI-guided biopsy (7.80% vs 3.05%, P <.0001), more likely to get a positive biopsy (41.25% vs 32.72%, P <.0001), and more likely to obtain an adequate number (by ≥12) of cores (90.25% vs 74.53%, P <.0001). UOFT remained a significant predictor of positivity when adjusting for patient age and race, PSA, 5-alpha-reductase-inhibitor use, year of biopsy, years in practice, and type of biopsy (MRI or transrectal ultrasound guided). UOFT also predicted higher-risk biopsy (Gleason sum ≥7), adjusting for the same variables, though this association lost significance when adjusting for adequacy of biopsy. The learning curve to achieve a higher percentage of positive biopsies was steeper for nonurologic oncology fellowship trained than for UOFT urologists. CONCLUSION: UOFT is associated with higher diagnostic yield on prostate biopsy, higher uptake of MRI-guided biopsy, and less steep learning curve. This may be due to patient selection, technique, or, as we demonstrate here, adherence to guidelines.
Assuntos
Educação , Bolsas de Estudo , Biópsia Guiada por Imagem/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Urologia/educação , Idoso , Competência Clínica , Erros de Diagnóstico/prevenção & controle , Educação/métodos , Educação/normas , Bolsas de Estudo/métodos , Bolsas de Estudo/estatística & dados numéricos , Humanos , Curva de Aprendizado , Imagem por Ressonância Magnética Intervencionista/métodos , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Ultrassonografia de Intervenção/métodos , Estados UnidosRESUMO
OBJECTIVES: To compare the incidence of benign uretero-enteric anastomotic strictures between open cystectomy, robotic cystectomy with extracorporeal urinary diversion, and robotic cystectomy with intracorporeal urinary diversion. The effect of surgeon learning curve on stricture incidence following intracorporeal diversion was investigated as a secondary outcome. PATIENTS AND METHODS: Patients who underwent radical cystectomy at an academic hospital between 2011 and 2018 were retrospectively reviewed. The primary outcome, incidence of anastomotic stricture over time, was assessed by a multivariable Cox proportional hazards regression. A Cox regression model adjusting for sequential case number in a surgeon's experience was used to assess intracorporeal learning curve. RESULTS: Nine hundred sixty-eight patients were included: 279 open, 382 robotic extracorporeal, and 307 robotic intracorporeal. Benign stricture incidence was 11.3% overall: 26 (9.3%) after open, 43 (11.3%) after robotic extracorporeal, and 40 (13.0%) after robotic intracorporeal. An intracorporeal approach was associated with anastomotic stricture on multivariable analysis (HR 1.66; P = .05). After 75 intracorporeal cases, stricture incidence declined from 17.5% to 4.9%. Higher sequential case volume was independently associated with reduced stricture incidence (Hazard Ratio per 10 cases: 0.90; P = .02). CONCLUSION: An intracorporeal approach to urinary reconstruction following robotic radical cystectomy was associated with an increased risk of benign uretero-enteric anastomotic stricture. In surgeons' early experience with intracorporeal diversion the difference in stricture incidence was more pronounced compared to alternative approaches; however, increased intracorporeal case volume was associated with a decline in stricture incidence leading to a modest difference between the 3 surgical approaches overall.
Assuntos
Cistectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Derivação Urinária/efeitos adversos , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Cistectomia/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Ureter/cirurgia , Bexiga Urinária/cirurgia , Derivação Urinária/métodosRESUMO
PURPOSE: Studies suggest that the antitumor effect of bacillus Calmette-Guerin depends on bacillus Calmette-Guerin attachment to fibronectin at fibrin clot formation sites and medications that impact fibrin clot formation may modify bacillus activity. We evaluated the impact of fibrin clot inhibitors on the clinical efficacy of bacillus Calmette-Guerin. MATERIALS AND METHODS: We reviewed the records of 907 consecutive patients treated with bacillus Calmette-Guerin between 1990 and 2006. Time to disease recurrence and progression to surgery were compared in patients who did and did not receive fibrin clot inhibitors by Kaplan-Meier methods and multivariate Cox regression models. RESULTS: Overall 221 patients (24%) received at least 1 fibrin clot inhibitor, including 170, 34 and 52 on aspirin, clopidogrel and warfarin, respectively. Patients on warfarin had shorter time to progression than patients not on warfarin (median 2.1 vs 9.0 years, p <0.005). Patients on aspirin had a significantly improved 5-year probability of freedom from surgery (66% vs 56%, p = 0.029). On multivariate analysis warfarin was associated with an increased risk of progression to surgery (HR 1.89, 95% CI 1.31, 2.74, p = 0.0007), while aspirin was associated with a decreased risk (HR 0.71, 95% CI 0.52, 0.96, p = 0.024). Warfarin alone was associated with an increased risk of tumor recurrence (HR 1.39, 95% CI 1.00, 1.94, p = 0.047). CONCLUSIONS: These data suggest that the risks of recurrence and progression to surgery after bacillus Calmette-Guerin are higher in patients on warfarin, while the risk of progression is lower in patients on aspirin. These findings may have important treatment implications in patients in whom bacillus Calmette-Guerin is contemplated.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anticoagulantes/farmacologia , Aspirina/farmacologia , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Fibrinolíticos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Neoplasias da Bexiga Urinária/tratamento farmacológico , Varfarina/farmacologia , Idoso , Clopidogrel , Interações Medicamentosas , Feminino , Humanos , Masculino , Estudos Retrospectivos , Ticlopidina/farmacologiaRESUMO
PURPOSE: For select men with low risk prostate cancer active surveillance is more often being considered a management strategy. In a multicenter retrospective study we evaluated the actuarial rates and predictors of remaining on active surveillance, the incidence of cancer progression and the pathological findings of delayed radical prostatectomy. MATERIALS AND METHODS: A cohort of 262 men from 4 institutions met the inclusion criteria of age 75 years or younger, prostate specific antigen 10 ng/ml or less, clinical stage T1-T2a, biopsy Gleason sum 6 or less, 3 or less positive cores at diagnostic biopsy, repeat biopsy before active surveillance and no treatment for 6 months following the repeat biopsy. Active surveillance started on the date of the second biopsy. Actuarial rates of remaining on active surveillance were calculated and univariate Cox regression was used to assess predictors of discontinuing active surveillance. RESULTS: With a median followup of 29 months 43 patients ultimately received active treatment. The 2 and 5-year probabilities of remaining on active surveillance were 91% and 75%, respectively. Patients with cancer on the second biopsy (HR 2.23, 95% CI 1.23-4.06, p = 0.007) and a higher number of cancerous cores from the 2 biopsies combined (p = 0.002) were more likely to undergo treatment. Age, prostate specific antigen, clinical stage, prostate volume and number of total biopsy cores sampled were not predictive of outcome. Skeletal metastases developed in 1 patient 38 months after starting active surveillance. Of the 43 patients undergoing delayed treatment 41 (95%) are without disease progression at a median of 23 months following treatment. CONCLUSIONS: With a median followup of 29 months active surveillance for select patients appears to be safe and associated with a low risk of systemic progression. Cancer at restaging biopsy and a higher total number of cancerous cores are associated with a lower likelihood of remaining on active surveillance. A restaging biopsy should be strongly considered to finalize eligibility for active surveillance.
Assuntos
Vigilância da População , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To review the outcomes of surgery for renal angiomyolipoma (AML, a benign renal neoplasm that often appears as an enhancing renal mass on imaging) removed at a centre that manages AML conservatively, as typically the presence of tumour fat content detected on imaging leads to its diagnosis, but occasionally these tumours resemble conventional RCC, leading to their surgical extirpation. PATIENTS AND METHODS: We retrospectively report data on 44 consecutive patients who had renal surgery with a pathological diagnosis of AML at our institution from 1988 to 2008. Patient demographics, intraoperative variables and postoperative outcomes are reported. RESULTS: Of the 44 patients (40 women, 91%, and four men, 9%), most were asymptomatic (36, 82%), were unsuspected on imaging (40, 91%), had a solitary lesion (38, 86%), and all had a normal contralateral kidney. Patients had either a partial nephrectomy (38, 86%) or radical nephrectomy (six, 14%). The median (range) tumour size was 2.5 (0.6-19) cm. Perioperative complications occurred in 10 patients (23%), and a total of seven renal units (16%) were lost. Ten patients (23%) had chronic kidney disease (CKD) before surgery, while new onset CKD developed in six (14%) at the last follow-up. There were no recurrences and there was one unrelated death at a median follow-up of 28 months. CONCLUSIONS: AML is a benign renal neoplasm that should be treated conservatively. Surgical intervention should be avoided, when possible, as it can lead to perioperative complications, loss of renal units, and development of CKD.