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1.
Urol Oncol ; 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35690547

RESUMO

PURPOSE: The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS: We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS: The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS: Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

3.
Lancet Oncol ; 23(7): 910-918, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35714666

RESUMO

BACKGROUND: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer. METHODS: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting. FINDINGS: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths. INTERPRETATION: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term. FUNDING: Insightec and the National Cancer Institute.

4.
Eur Urol ; 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35637041

RESUMO

BACKGROUND: Prostate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors. OBJECTIVE: To examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle. DESIGN, SETTING, AND PARTICIPANTS: We prospectively followed 12 411 genotyped men in the Health Professionals Follow-up Study (1993-2019) and the Physicians' Health Study (1983-2010). Genetic risk of prostate cancer was quantified using a polygenic risk score (PRS). A healthy lifestyle was defined by healthy weight, vigorous physical activity, not smoking, and a healthy diet. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall and lethal prostate cancer events (metastatic disease/prostate cancer-specific death) were analyzed using time-to-event analyses estimating hazard ratios (HRs) and lifetime risks. RESULTS AND LIMITATIONS: During 27 yr of follow-up, 3005 overall prostate cancer and 435 lethal prostate cancer events were observed. The PRS enabled risk stratification not only for overall prostate cancer, but also for lethal disease with a four-fold difference between men in the highest and lowest quartiles (HR, 4.32; 95% confidence interval [CI], 3.16-5.89). Among men in the highest PRS quartile, adhering to a healthy lifestyle was associated with a decreased rate of lethal prostate cancer (HR, 0.55; 95% CI, 0.36-0.86) compared with having an unhealthy lifestyle, translating to a lifetime risk of 1.6% (95% CI, 0.8-3.1%) among the healthy and 5.3% (95% CI, 3.6-7.8%) among the unhealthy. Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer. CONCLUSIONS: Our findings suggest that a genetic predisposition for prostate cancer is not deterministic for a poor cancer outcome. Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer. PATIENT SUMMARY: This study examined whether the genetic risk of prostate cancer can be attenuated by a healthy lifestyle including a healthy weight, regular exercise, not smoking, and a healthy diet. We observed that adherence to a healthy lifestyle reduced the risk of metastatic disease and prostate cancer death among men at the highest genetic risk. We conclude that men at a high genetic risk of prostate cancer may benefit from adhering to a healthy lifestyle.

5.
Urol Clin North Am ; 49(2): 309-321, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35428436

RESUMO

Androgen deprivation therapy, used alone or in combination, inhibits androgen activity either upstream at the level of the pituitary gland or downstream by disrupting the androgenesis pathway in the adrenal or androgen activity in prostate cells. Its appropriate utilization varies depending on disease stage, aggressivity, and resistance. Special consideration should be given to side effects, as it can affect patients' quality of life and their treatment of other conditions.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/efeitos adversos , Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida
6.
Cancer Epidemiol Biomarkers Prev ; 31(7): 1460-1465, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35255119

RESUMO

BACKGROUND: How 5-alpha reductase inhibitor (5-ARI) use influences prostate cancer mortality is unclear. The objective of this study was to determine whether men taking 5-ARIs with regular health care access have increased prostate cancer mortality. METHODS: We undertook two analyses in the Health Professionals Follow-up Study examining 5-ARI use, determined by biennial questionnaires, and prostate cancer. A cohort analysis followed 38,037 cancer-free men for prostate cancer incidence from 1996 through January 2017 and mortality through January 2019. A case-only analysis followed 4,383 men with localized/locally advanced prostate cancer for mortality over a similar period. HRs and 95% confidence intervals (CI) were calculated for prostate cancer incidence and mortality. RESULTS: Men using 5-ARIs underwent more PSA testing, prostate exams and biopsies. Over 20 years of follow-up, 509 men developed lethal disease (metastases or prostate cancer death). Among men initially free from prostate cancer, 5-ARI use was not associated with developing lethal disease [HR, 1.02; 95% confidence interval (CI), 0.71-1.46], but was associated with reduced rates of overall and localized disease (HR, 0.71; 0.60-0.83). Among men diagnosed with prostate cancer, there was no association between 5-ARI use and cancer-specific (HR, 0.78; 95% CI, 0.48-1.27) or overall survival (HR, 0.88; 95% CI, 0.72-1.07). CONCLUSIONS: Men using 5-ARIs were less likely to be diagnosed with low-risk prostate cancer, without increasing long-term risk of lethal prostate cancer or cancer-specific death after diagnosis. IMPACT: Our results provide evidence that 5-ARI use is safe with respect to prostate cancer mortality in the context of regular health care access. See related commentary by Hamilton, p. 1259.

7.
Urol Int ; : 1-7, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35306500

RESUMO

INTRODUCTION: The aim of this study was to examine the relationship between duration of surgical intervention and postoperative complications in radical cystectomy (RC). We hypothesized that the complication rate increases with longer operative time. METHODS: We analyzed the National Surgical Quality Improvement Program database 2011-2017 to identify all patients who underwent RC. Clinicodemographic characteristics, operative time, and perioperative complications using the Clavien-Dindo Classification (CDC) were abstracted. We fit a generalized linear model with linear splines for operative time to analyze if the relationship between operative time and probability of complication changed over time. RESULTS: A total of 10,520 RC patients were identified with a mean operative time of 5.5 h (standard deviation 2.03). In 55% and 18.2%, any complication and major complications (CDC ≥3) occurred within 30 days postoperatively, respectively. The spline regression model for any complication showed an almost linear relationship between the complication rate and operative time, ranging from 55% at 2.5 h to 82% at 10 h. For major complications, the model revealed the inflection point (knot) at 4.5 h, which corresponds to the lowest complication rate with 15%. Operative times at the extremes of the distribution had higher complication rates: 17.5% if <2.5 h and 28% if >10 h. DISCUSSION/CONCLUSION: Operative time of RC is associated with postoperative complications. Though many factors impact the duration of surgery, surgeries that lasted between 4 and 5 h had trend toward the lowest complication rates. Attention to factors impacting operative time may allow surgeons to identify strategies for optimizing surgical care and reducing complications after RC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35152271

RESUMO

BACKGROUND: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets. METHODS: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured. RESULTS: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively. CONCLUSIONS: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

9.
Sci Adv ; 8(7): eabl9794, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35179959

RESUMO

Current targeted cancer therapies are largely guided by mutations of a single gene, which overlooks concurrent genomic alterations. Here, we show that RNASEH2B, RB1, and BRCA2, three closely located genes on chromosome 13q, are frequently deleted in prostate cancer individually or jointly. Loss of RNASEH2B confers cancer cells sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition due to impaired ribonucleotide excision repair and PARP trapping. When co-deleted with RB1, however, cells lose their sensitivity, in part, through E2F1-induced BRCA2 expression, thereby enhancing homologous recombination repair capacity. Nevertheless, loss of BRCA2 resensitizes RNASEH2B/RB1 co-deleted cells to PARP inhibition. Our results may explain some of the disparate clinical results from PARP inhibition due to interaction between multiple genomic alterations and support a comprehensive genomic test to determine who may benefit from PARP inhibition. Last, we show that ATR inhibition can disrupt E2F1-induced BRCA2 expression and overcome PARP inhibitor resistance caused by RB1 loss.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Proteína BRCA2 , Reparo do DNA , Replicação do DNA , Genes BRCA2 , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Proteínas de Ligação a Retinoblastoma/genética , Ribonuclease H , Ubiquitina-Proteína Ligases/genética
10.
Prostate Cancer Prostatic Dis ; 25(2): 320-326, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35075214

RESUMO

BACKGROUND: Metabolic syndrome and its pharmacologic treatment can potentially influence the progression of prostate cancer in men receiving androgen deprivation therapy (ADT). We aimed to evaluate the association between metabolic syndrome and its pharmacologic treatment with time to castration-resistant prostate cancer (CRPC). METHODS: We identified 409 men with metastatic castration-sensitive prostate cancer receiving first line ADT from 1996 to 2014 at our institution. Information concerning metabolic syndrome, statin use, aspirin use, and metformin use at initiation of ADT was collected from medical records. Time to CRPC was defined as the duration between initiating ADT and diagnosis of CRPC based on the Prostate Cancer Working Group 3 definition. Flexible parametric survival models were used to calculate hazard ratios (HR, and 95% confidence intervals, CI) of the association between metabolic conditions and time from ADT initiation to CRPC. RESULTS: During a median follow-up of 59 months, 87% (N = 356) men progressed to CRPC. Median time to CRPC was 19 months. Fifty-six percent of men met the definition of metabolic syndrome. Controlling for demographic and prostate cancer-specific variables, metabolic syndrome was associated with shorter time to CRPC (HR 1.41, 95% CI 1.09-1.81). Importantly, in men with metabolic syndrome, statin use was associated with a slower progression to CRPC (HR 0.70, 95% CI 0.49-0.98). CONCLUSIONS: Our study suggests that metabolic syndrome is a risk factor for earlier progression from castration-sensitive to castration-resistant prostate cancer and raises the possibility that treatment, such as statin use, may slow the time to progression.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Metabólica , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Gradação de Tumores , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Estudos Retrospectivos
11.
Eur Urol ; 81(5): 458-462, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35031163

RESUMO

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10-4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10-5; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10-4; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Próstata , Estudos de Casos e Controles , Predisposição Genética para Doença , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Humanos , Masculino , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
12.
JNCI Cancer Spectr ; 6(1)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35079693

RESUMO

Background: Altered DNA damage response (DDR) has emerged as an important mechanism for the development of aggressive prostate cancer among men of European ancestry but not other ancestry groups. Because common mechanisms for aggressive disease are expected, we explored a large panel of DDR genes and pathways to demonstrate that DDR alterations contribute to development of aggressive prostate cancer in both African American and European American men. Methods: We performed a case-case study of 764 African American and European American men with lethal or indolent prostate cancer treated at 4 US hospitals. We calculated carrier frequencies of germline pathogenic or likely pathogenic sequence variants within 306 DDR genes, summarized by DDR pathway, and compared lethal cases against indolent cases using 2-sided Fisher's exact tests. Secondary analysis examined if carrier frequencies differed by ancestry. Results: Lethal cases were more likely to carry a pathogenic sequence variant in a DDR gene compared with indolent cases (18.5% vs 9.6%, P = 4.30 × 10-4), even after excluding BRCA2 (14.6% vs 9.6%, P = .04). The carrier frequency was similar among lethal cases of African (16.7% including and 15.8% excluding BRCA2) and lethal cases of European (19.3% including and 14.2% excluding BRCA2) ancestry. Three DDR pathways were statistically significantly associated with lethal disease: homologous recombination (P = .003), Fanconi anemia (P = .002), and checkpoint factor (P = .02). Conclusions: Our findings suggest that altered DDR is an important mechanism for aggressive prostate cancer not only in men of European but also of African ancestry. Therefore, interrogation of entire DDR pathways is needed to fully characterize and better define genetic risk of lethal disease.


Assuntos
Afro-Americanos/genética , Distúrbios no Reparo do DNA/genética , Reparo do DNA/genética , Neoplasias da Próstata/genética , /genética , Idoso , Reparo de Erro de Pareamento de DNA/genética , Anemia de Fanconi/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/etnologia
13.
J Natl Cancer Inst ; 114(2): 310-313, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33630063

RESUMO

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen.


Assuntos
Vacinas Anticâncer , Neoplasias da Próstata , Vacinas Anticâncer/uso terapêutico , Humanos , Imunoterapia , Leucócitos Mononucleares , Masculino , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Extratos de Tecidos/farmacologia , Extratos de Tecidos/uso terapêutico , Estados Unidos
14.
Eur Urol ; 81(5): 466-473, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34953602

RESUMO

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a rare but serious event following definitive radiation for prostate cancer. Radiation-associated MIBC (RA-MIBC) can be difficult to manage given the challenges of delivering definitive therapy to a previously irradiated pelvis. The genomic landscape of RA-MIBC and whether it is distinct from non-RA-MIBC are unknown. OBJECTIVE: To define mutational features of RA-MIBC and compare the genomic landscape of RA-MIBC with that of non-RA-MIBC. DESIGN, SETTING, AND PARTICIPANTS: We identified patients from our institution who received radiotherapy for prostate cancer and subsequently developed MIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed whole exome sequencing of bladder tumors from RA-MIBC patients. Tumor genetic alterations including mutations, copy number alterations, and mutational signatures were identified and were compared with genetic features of non-RA-MIBC. We used the Kaplan-Meier method to estimate recurrence-free (RFS) and overall (OS) survival. RESULTS AND LIMITATIONS: We identified 19 RA-MIBC patients with available tumor tissue (n = 22 tumors) and clinical data. The median age was 76 yr, and the median time from prostate cancer radiation to RA-MIBC was 12 yr. The median RFS was 14.5 mo and the median OS was 22.0 mo. Compared with a cohort of non-RA-MIBC analyzed in parallel, there was no difference in tumor mutational burden, but RA-MIBCs had a significantly increased number of short insertions and deletions (indels) consistent with previous radiation exposure. We identified mutation signatures characteristic of APOBEC-mediated mutagenesis, aging, and homologous recombination deficiency. The frequency of mutations in many known bladder cancer genes, including TP53, KDM6A, and RB1, as well as copy number alterations such as CDKN2A loss was similar in RA-MIBC and non-RA-MIBC. CONCLUSIONS: We identified unique mutational properties that likely contribute to the distinct biological and clinical features of RA-MIBC. PATIENT SUMMARY: Bladder cancer is a rare but serious diagnosis following radiation for prostate cancer. We characterized genetic features of bladder tumors arising after prostate radiotherapy, and identify similarities with and differences from bladder tumors from patients without previous radiation.


Assuntos
Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Idoso , Feminino , Genômica/métodos , Humanos , Masculino , Músculos/patologia , Invasividade Neoplásica , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/radioterapia
15.
J Urol ; 207(1): 127-136, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433304

RESUMO

PURPOSE: Our goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study. MATERIALS AND METHODS: We evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003-2006) and the PROST-QA/RP2 cohorts (2010-2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications. RESULTS: Demographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p <0.01) and nerve sparing (94% vs 89%; p <0.01). RALP vs ORP subjects experienced less mean intraoperative blood loss (192 vs 805 mL; p <0.01), shorter mean hospital stay (1.6 vs 2.1 days; p <0.01), and fewer blood transfusions (1% vs 4%; p <0.01), wound infections (2% vs 4%; p=0.02), other infections (1% vs 4%; p <0.01), deep venous thromboses (0.5% vs 2%; p=0.04), and bladder neck contractures requiring dilation (1.6% vs 8.3%; p <0.01). RALP subjects reported less pain (p=0.04), less activity interference (p <0.01) and higher incision satisfaction (p <0.01). Surgical approach (RALP vs ORP) was not a significant predictor of longitudinal HRQOL change in any HRQOL domain. CONCLUSIONS: In high-volume academic centers, RALP and ORP patients may expect similar long-term HRQOL outcomes. Overall, RALP patients have less pain, shorter hospital stays, and fewer post-surgical complications such as blood transfusions, infections, deep venous thromboses, and bladder neck contractures.


Assuntos
Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
16.
Am J Clin Pathol ; 156(4): 550-558, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424955

RESUMO

OBJECTIVES: Tumor size has long been used in the management decision-making of patients with renal masses. Active surveillance had recently gained traction in selected patients with tumor size of 4 cm or less. Adverse histopathologic characteristics in papillary renal cell carcinoma (PRCC) have been shown to correlate with worse prognosis. We aimed to study whether such features in small PRCCs provide additional prognostic information. METHODS: Nephrectomies from our institution were collected and reviewed to evaluate for adverse histopathologic features. Clinical follow-up information was collected for all cases. Relationships between the variables were examined by Wilcoxon test and logistic regression. RESULTS: We identified 291 consecutive cases of PRCC. Adverse tumor histopathologic characteristics were significantly related to size. In PRCCs with size greater than 4 cm, there were more cases with high World Health Organization/International Society of Urological Pathology grade and necrosis. Adverse histologic features are less commonly seen in small PRCC and are not associated with lower disease-free survival or disease-specific survival. CONCLUSIONS: Identification of these features in small PRCCs (≤4 cm) through needle core biopsy examination would not provide additional prognostic information in patients for whom active surveillance is considered. Clinical and radiologic follow-up in patients with small renal masses that have a known histologic diagnosis of PRCC should be sufficient.


Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Adulto , Biópsia com Agulha de Grande Calibre , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Prognóstico , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-34127801

RESUMO

BACKGROUND: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. MATERIALS AND METHODS: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. RESULTS: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings. CONCLUSION: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.

18.
Sci Rep ; 11(1): 11480, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075061

RESUMO

Preoperative assessment of the proximity of critical structures to the tumors is crucial in avoiding unnecessary damage during prostate cancer treatment. A patient-specific 3D anatomical model of those structures, namely the neurovascular bundles (NVB) and the external urethral sphincters (EUS), can enable physicians to perform such assessments intuitively. As a crucial step to generate a patient-specific anatomical model from preoperative MRI in a clinical routine, we propose a multi-class automatic segmentation based on an anisotropic convolutional network. Our specific challenge is to train the network model on a unique source dataset only available at a single clinical site and deploy it to another target site without sharing the original images or labels. As network models trained on data from a single source suffer from quality loss due to the domain shift, we propose a semi-supervised domain adaptation (DA) method to refine the model's performance in the target domain. Our DA method combines transfer learning and uncertainty guided self-learning based on deep ensembles. Experiments on the segmentation of the prostate, NVB, and EUS, show significant performance gain with the combination of those techniques compared to pure TL and the combination of TL with simple self-learning ([Formula: see text] for all structures using a Wilcoxon's signed-rank test). Results on a different task and data (Pancreas CT segmentation) demonstrate our method's generic application capabilities. Our method has the advantage that it does not require any further data from the source domain, unlike the majority of recent domain adaptation strategies. This makes our method suitable for clinical applications, where the sharing of patient data is restricted.


Assuntos
Redes Neurais de Computação , Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Tomografia Computadorizada por Raios X , Humanos , Masculino
19.
BMC Urol ; 21(1): 81, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001094

RESUMO

BACKGROUND: To examine one-year trajectories of urinary and sexual outcomes, and correlates of these trajectories, among prostate cancer patients treated by radical prostatectomy (RP). METHODS: Study participants were recruited from 2011 to 2014 at two US institutions. Self-reported urinary and sexual outcomes were measured at baseline before surgery, and 5 weeks, 6 months and 12 months after surgery, using the modified Expanded Prostate Cancer Index Composite-50 (EPIC-50). Changes in EPIC-50 scores from baseline were categorized as improved (beyond baseline), maintained, or impaired (below baseline), using previously-reported minimum clinically important differences. RESULTS: Of the 426 eligible participants who completed the baseline survey, 395 provided data on at least one EPIC-50 sub-scale at 5 weeks and 12 months, and were analyzed. Although all mean EPIC-50 scores declined markedly 5 weeks after surgery and then recovered to near (incontinence-related outcomes) or below (sexual outcomes) baseline levels by 12 months post-surgery, some men experienced improvement beyond their baseline levels on each sub-scale (3.3-51% depending on the sub-scale). Having benign prostatic hyperplasia (BPH) at baseline (prostate size ≥ 40 g; an International Prostate Symptom Index Score ≥ 8; or using BPH medications) was associated with post-surgical improvements in voiding dysfunction-related bother at 5 weeks (OR = 3.9, 95% CI: 2.1-7.2) and 12 months (OR = 3.3, 95% CI: 2.0-5.7); and in sexual bother at 5 weeks (OR = 5.7, 95% CI:1.7-19.3) and 12 months (OR = 3.0, 95% CI: 1.2-7.1). CONCLUSIONS: Our findings provide additional support for considering baseline BPH symptoms when selecting the best therapy for early-stage prostate cancer.


Assuntos
Prostatectomia , Neoplasias da Próstata/cirurgia , Idoso , Disfunção Erétil/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Prostatectomia/métodos , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/epidemiologia
20.
J Clin Endocrinol Metab ; 106(8): 2171-2186, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34019661

RESUMO

BACKGROUND: Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer. METHODS: In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers. RESULTS: Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73). CONCLUSIONS: Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.


Assuntos
Androgênios/deficiência , Sobreviventes de Câncer , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Receptores Androgênicos/metabolismo , Idoso , Androgênios/sangue , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
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