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BACKGROUND: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis. CONCLUSIONS: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.
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Población Negra , Prostatectomía , Neoplasias de la Próstata , Población Blanca , Factores de Edad , Anciano , Análisis de Varianza , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Clasificación del Tumor , Supervivencia sin Progresión , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: We examined rates of Grade Group 4 downgrading at radical prostatectomy among men diagnosed with high and very high risk prostate cancer at biopsy. MATERIALS AND METHODS: A pooled cohort of 1,776 patients from 3 tertiary referral centers who underwent radical prostatectomy for National Comprehensive Cancer Network® high risk (prostate specific antigen greater than 20 ng/ml, or Grade Group 4-5, or clinical stage T3 or greater) or very high risk (primary Gleason pattern 5, or more than 4 biopsy cores with Grade Group 4-5, or 2 or more high risk features) disease from 2005 to 2015 were reviewed. Overall 893 patients with Grade Group 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to Grade Group 3 or less at radical prostatectomy. RESULTS: Overall 333 (45%) cases were downgraded to Grade Group 3 or less at radical prostatectomy. Of these cases 198 (27%) had concordant Grade Group 4 biopsy and radical prostatectomy pathology and 195 (27%) were upgraded at radical prostatectomy to Grade Group 5. Of high risk cases with biopsy Grade Group 4 disease 49% had any downgrading vs 29% of very high risk cases (p <0.0001). Downgrading to Grade Group 2 or less occurred in 16% (98 of 604) of high risk and 7% (8 of 122) of very high risk cases (p <0.01). Downgraded cases had a lower prostate specific antigen, fewer positive biopsy cores and lower clinical stage (p <0.01). On multivariable analysis fewer positive biopsy cores were significantly associated with downgrading at radical prostatectomy (p <0.01). CONCLUSIONS: In this cohort of patients with high risk/very high risk prostate cancer, downgrading from biopsy Grade Group 4 at radical prostatectomy occurred less frequently than in other published reports. Any downgrading was significantly less common in very high risk compared to high risk patients, and downgrading to Grade Group 2 or less occurred in a minority of cases in high risk and very high risk patients.
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Próstata/patología , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Biopsia , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Prostatectomía/métodos , Estudios Retrospectivos , Medición de RiesgoRESUMEN
BACKGROUND: Among men with localized high-risk prostate cancer (PCa), patients who meet very high-risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single-center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression. METHODS: Patients with high-risk PCa undergoing RP (2005-2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high-risk criteria were a clinical stage of T3 to T4, a prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high-risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer-specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models. RESULTS: Among 1981 patients with high-risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P < .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08-3.72), CSM (6.77; 95% CI, 2.91-15.7), and overall mortality (2.44; 95% CI, 1.56-3.80; P < .001 for all comparisons). CONCLUSIONS: In a validation study of patients who underwent treatment for high-risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes.
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Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare radical prostatectomy (RP) vs radiotherapy (RT) with androgen-deprivation therapy (ADT) in the setting of patients with high-risk and very high-risk (VHR) prostate cancer who were deemed eligible for either therapy and made a treatment choice after consultation in a multidisciplinary prostate cancer clinic (MDPCC), and to compare the MDPCC patients' outcomes to a matched Surveillance, Epidemiology and End Results (SEER) cohort. PATIENTS AND METHODS: Prospectively collected, retrospective study comparing patients who underwent RP (231 patients) vs RT+ADT (73) from 2004 to 2013. Biochemical recurrence (BCR), local recurrence, distant metastasis failure, and overall survival (OS) were calculated for each treatment group overall and according to National Comprehensive Cancer Network risk strata. A propensity score matched comparison with a SEER cohort was performed for OS. RESULTS: There was no difference in local recurrence (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.0-7.9; P = 0.06), distant metastasis failure (HR 2.5, 95% CI 0.8-7.8; P = 0.1) and OS (HR 1.35, 95% CI 0.4-4.8; P = 0.6) between patients undergoing RP vs RT+ADT. Patients treated via the MDPCC survived on average 16.9 months (95% CI 13.1-20.8) longer than those in the matched SEER cohort. CONCLUSIONS: Long-term outcomes appear similar amongst patients with high-risk and VHR prostate cancer deemed eligible for either RP or RT, and treated after consultation in a MDPCC. Outcomes of the MDPCC patients were superior to those of the matched SEER cohort.
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Prostatectomía , Neoplasias de la Próstata , Radioterapia Adyuvante , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Prostatectomía/efectos adversos , Prostatectomía/mortalidad , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/mortalidad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine whether time from diagnosis to treatment impacted outcomes in a multicentre cohort of high- and very-high-risk (VHR) patients with prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: In all, 1392 patients from three tertiary centres who underwent RP for either high-risk or VHR disease, from 2005 to 2015, were identified. The cohort was divided into tertiles based on time from diagnostic biopsy to RP. Cumulative incidence of biochemical recurrence (BCR), metastasis, and prostate cancer-specific mortality (PCSM) were calculated for each tertile. The Kaplan-Meier method was used to evaluate for differences in all-cause mortality (ACM) amongst tertiles. Competing risks regression models, as well as Cox proportional hazards regression models, were fitted to assess the association between time-to-event outcomes and patient characteristics. RESULTS: The median (interquartile range [IQR]) time from biopsy to RP was 68 (50-94) days. The median (IQR) follow-up was 31 (12.1-55.7) months. The cumulative incidence of BCR (P = 0.14), metastasis (P = 0.15), and PCSM (P = 0.69) did not differ amongst time-to-treatment tertiles of VHR patients. Also, Kaplan-Meier estimates of ACM (P = 0.53) did not differ amongst time-to-treatment tertiles. Similarly, BCR, metastasis, PCSM, and ACM did not significantly differ amongst time-to-treatment tertiles in multivariable modelling. CONCLUSION: In this pooled meta-dataset of patients with high-risk or VHR prostate cancer, time from diagnosis to RP did not appear to significantly contribute to differences in clinical outcomes. This finding supports the safety of enrollment of such patients into neoadjuvant clinical trials.
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Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Tiempo de Tratamiento , Anciano , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: HSD3B1 (1245A>C) has been mechanistically linked to castration-resistant prostate cancer because it encodes an altered enzyme that augments dihydrotestosterone synthesis from non-gonadal precursors. We postulated that men inheriting the HSD3B1 (1245C) allele would exhibit resistance to androgen-deprivation therapy (ADT). METHODS: In this multicohort study, we determined HSD3B1 genotype retrospectively in men treated with ADT for post-prostatectomy biochemical failure and correlated genotype with long-term clinical outcomes. We used data and samples from prospectively maintained prostate cancer registries at the Cleveland Clinic (Cleveland, OH, USA; primary study cohort) and the Mayo Clinic (Rochester, MN, USA; post-prostatectomy and metastatic validation cohorts). In the post-prostatectomy cohorts, patients of any age were eligible if they underwent prostatectomy between Jan 1, 1996, and Dec 31, 2009 (at the Cleveland Clinic; primary cohort), or between Jan 1, 1987, and Dec 31, 2011 (at the Mayo Clinic; post-prostatectomy cohort) and were treated with ADT for biochemical failure or for non-metastatic clinical failure. In the metastatic validation cohort, patients of any age were eligible if they were enrolled at Mayo Clinic between Sept 1, 2009, and July 31, 2013, with metastatic castration-resistant prostate cancer. The primary endpoint was progression-free survival according to HSD3B1 genotype. We did prespecified multivariable analyses to assess the independent predictive value of HSD3B1 genotype on outcomes. FINDINGS: We included and genotyped 443 patients: 118 in the primary cohort (who underwent prostatectomy), 137 in the post-prostatectomy validation cohort, and 188 in the metastatic validation cohort. In the primary study cohort, median progression-free survival diminished as a function of the number of variant alleles inherited: 6·6 years (95% CI 3·8-not reached) in men with homozygous wild-type genotype, 4·1 years (3·0-5·5) in men with heterozygous variant genotype, and 2·5 years (0·7 to not reached) in men with homozygous variant genotype (p=0·011). Relative to the homozygous wild-type genotype, inheritance of two copies of the variant allele was predictive of decreased progression-free survival (hazard ratio [HR] 2·4 [95% CI 1·1-5·3], p=0·029), as was inheritance of one copy of the variant allele (HR 1·7 [1·0-2·9], p=0·041). Findings were similar for distant metastasis-free survival and overall survival. The effect of the HSD3B1 genotype was independently confirmed in the validation cohorts. INTERPRETATION: Inheritance of the HSD3B1 (1245C) allele that enhances dihydrotestosterone synthesis is associated with prostate cancer resistance to ADT. HSD3B1 could therefore potentially be a powerful genetic biomarker capable of distinguishing men who are a priori likely to fare favourably with ADT from those who harbour disease liable to behave more aggressively, and who therefore might warrant early escalated therapy. FUNDING: Prostate Cancer Foundation, National Institutes of Health, US Department of Defense, Howard Hughes Medical Institute, American Cancer Society, Conquer Cancer Foundation of the American Society of Clinical Oncology, Cleveland Clinic Research Programs Committee and Department of Radiation Oncology, Gail and Joseph Gassner Development Funds.
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Antagonistas de Andrógenos/uso terapéutico , Complejos Multienzimáticos/genética , Progesterona Reductasa/genética , Neoplasias de la Próstata/tratamiento farmacológico , Esteroide Isomerasas/genética , Anciano , Estudios de Cohortes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Prostatectomía , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: The increased clinical availability of a wide variety of molecular tests will potentially reshape the care of both men at risk for prostate cancer and men already diagnosed. It is imperative that clinicians be familiar with indications and clinical relevance of these tests. RECENT FINDINGS: The continued clinical validation in new and expanded clinical cohorts and reports of clinical experience with various molecular markers is a rapidly evolving body of literature. Results of large patient series demonstrate that these markers increase the precision of available information used in clinical management decision-making and joint physician-patient discussions regarding treatment options. SUMMARY: These tests may make more accurate management decisions possible for those whom have been 'over-diagnosed' with biologically indolent disease which represents an exceptionally small mortality risk. They also may aid in more accurate diagnosis of significant cancer, as well as more precise application of adjuvant therapy.
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Biomarcadores de Tumor/análisis , Técnicas de Diagnóstico Molecular/métodos , Próstata/fisiopatología , Neoplasias de la Próstata/diagnóstico , Biopsia , Detección Precoz del Cáncer , Humanos , Masculino , Técnicas de Diagnóstico Molecular/economía , Clasificación del Tumor , Polimorfismo de Nucleótido Simple , Próstata/metabolismo , Próstata/patología , Próstata/fisiología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Medición de Riesgo , Sensibilidad y Especificidad , Espera VigilanteRESUMEN
The recent introduction of a variety of molecular tests will potentially reshape the care of patients with prostate cancer. These tests may make more accurate management decisions possible for those patients who have been "overdiagnosed" with biologically indolent disease, which represents an exceptionally small mortality risk. There is a wide range of possible applications of these tests to different clinical scenarios in patient populations managed with active surveillance. Cancer 2015;121:3435-43. © 2015 American Cancer Society.
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Neoplasias de la Próstata/epidemiología , Espera Vigilante/métodos , Expresión Génica , Humanos , Masculino , Medicina de Precisión , Neoplasias de la Próstata/genética , Medición de RiesgoRESUMEN
INTRODUCTION: To identify a cohort of chronic pelvic pain syndrome (CPPS) patients who considered their symptoms completely resolved and analyze their demographics, clinical phenotype, treatments and NIH-Chronic Prostatitis Symptom Index (CPSI) scores. MATERIALS AND METHODS: We identified 35 CPPS patients who at the follow up, reported their symptoms completely resolved ('cured'). Demographics, UPOINT phenotypes, treatments, and CPSI scores were examined. We also compared these variables to a database of 220 previously evaluated CPPS patients. RESULTS: Patients ranged in age from 19 to 72 years. Median follow up was 12 months. Mean change in CPSI sub scores before and after therapy were pain 9.7 ± 3.8 to 2.7 ± 2.9, urinary 4.0 ± 2.8 to 1.1 ± 1.2, QoL 8.1 ± 2.7 to 2.3 ± 2.5, and total 21.8 ± 6.6 to 6.2 ± 1.0 (all p < 0.0001). Only 9 (26%) patients reported a total score of 0. Comparing this 'cured' group to a previously published cohort of phenotyped CPPS patients, the 'cured' group had lower starting total and pain CPSI scores (21.8 versus 25.0 p = 0.007; 9.7 versus 11.5 p = 0.006 respectively). CONCLUSIONS: Many men with CPPS can reach a subjective cure, however, the majority do not reach a CPSI score of 0. This group of "cured" patients is similar to our typical tertiary referral cohort in terms of age and phenotype but differs in having slightly lower pre-treatment CPSI scores.
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Dolor Crónico/terapia , Dolor Pélvico/terapia , Fenotipo , Adulto , Anciano , Enfermedad Crónica , Dolor Crónico/etiología , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Pélvico/etiología , Prostatitis/complicaciones , Calidad de Vida , Encuestas y Cuestionarios , Síndrome , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Diet and the gut microbiome have a complex interaction that generates metabolites with an unclear effect on lethal prostate cancer risk. Identification of modifiable risk factors for lethal prostate cancer is challenging given the long natural history of this disease and difficulty of prospectively identifying lethal cancers. METHODS: Mass spectrometry was performed on baseline serum samples collected from 173 lethal prostate cancer cases and 519 controls enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. Baseline serum levels of choline, carnitine, betaine, γ-butyrobetaine, crotonobetaine, phenylacetylglutamine, hippuric acid, and p-cresol sulfate were quantified and analyzed by quartile. Conditional multivariable logistic regression analysis associated analyte levels with lethal prostate cancer incidence after adjusting for body mass index and PSA. The Cochran-Armitage test evaluated analyte level trends across quartiles. RESULTS: Relative to those in the first quartile, cases with the highest baseline levels of choline (Q4 OR: 2.19; 95% CI, 1.23-3.90; P-trend: 0.005) and betaine (Q4 OR: 1.86; 95% CI, 1.05-3.30; P-trend: 0.11) exhibited increased odds of developing lethal prostate cancer. Higher baseline serum levels of phenylacetylglutamine (Q4 OR: 2.55; 95% CI, 1.40-4.64; P-trend: 0.003), a gut microbiome metabolite of phenylalanine with adrenergic activity, were also associated with lethal prostate cancer. CONCLUSIONS: Baseline serum levels of one-carbon methyl donors and adrenergic compounds resulting from human and gut microbiota-mediated metabolism are associated with increased lethal prostate cancer risk. IMPACT: Dietary composition, circulating metabolite levels, and downstream signaling pathways may represent modifiable risk factors associated with incident lethal prostate cancer. Beta-adrenergic blockade represents an additional target for oncologic risk reduction.
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Biomarcadores de Tumor/metabolismo , Microbioma Gastrointestinal , Tamizaje Masivo/métodos , Redes y Vías Metabólicas , Neoplasias de la Próstata/metabolismo , Anciano , Estudios de Casos y Controles , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
BACKGROUND: High-risk (HR) prostate cancer (PCa) is a heterogeneous disease leading to difficulties in designing appropriate inclusion criteria for clinical trials. OBJECTIVE: To describe clinical predictors of organ-confined disease in HR or very-high-risk (VHR) PCa patients staged with multiparametric magnetic resonance imaging with endorectal coil (mp-MRI-ER). DESIGN, SETTING, AND PARTICIPANTS: We reviewed 366 HR/VHR PCa patients who had preoperative mp-MRI-ER, and underwent radical prostatectomy and extended pelvic lymph node dissection between 2006 and 2015. INTERVENTION: Radical prostatectomy with preoperative mp-MRI-ER. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used multivariable logistic regression modeling to assess for associations with ≤ pT2N0 stage and multivariable cox modeling to assess for associations with biochemical failure. RESULTS AND LIMITATIONS: Of 366 patients, 132 had ≤ pT2N0 disease. For the entire cohort, negative staging mp-MRI-ER (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06-2.83, p = 0.03), lower prostate-specific antigen (PSA; OR 0.98, 95% CI 0.97-1.00, p = 0.02), and fewer cores of Gleason ≥8 cancer (OR 0.86, 95% CI 0.79-0.93, p = 0.0002) were associated with ≤pT2N0 disease. In HR patients only, negative mp-MRI-ER (OR 3.41, 95% CI 1.73-6.72, p = 0.0004) and fewer than four cores of Gleason ≥8 disease (OR 3.38, 95% CI 1.20-9.56, p = 0.02) were still associated with ≤pT2N0 disease. Lack of non-organ-confined disease on MRI was associated with superior biochemical recurrence-free survival (p = 0.02). Limitations of this study include lack of a central review or quality control of the MRI reporting. CONCLUSIONS: In HR PCa, negative staging mp-MRI-ER, fewer positive cores of Gleason >8, and lower PSA were significant predictors of pathologic organ-confined disease. Improved prediction of organ-confined disease in HR patients may allow for their inclusion into studies evaluating treatments from which they would otherwise be excluded based solely on their HR status. PATIENT SUMMARY: In patients with high-risk prostate cancer, prostate magnetic resonance imaging along with other clinical parameters may help determine which patients are likely to have disease confined to the prostate and thus be eligible for clinical trials that they otherwise might be excluded from based on their high-risk status alone.
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Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Radiocirugia , Estudios RetrospectivosRESUMEN
BACKGROUND: Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC). OBJECTIVE: To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC. DESIGN, SETTING, AND PARTICIPANTS: A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models. RESULTS AND LIMITATIONS: A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation. CONCLUSIONS: Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed. PATIENT SUMMARY: This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.
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Adenocarcinoma/terapia , Neoplasias de la Próstata/terapia , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Resultado del TratamientoRESUMEN
While radiotherapy with androgen deprivation therapy is the current standard of care for the treatment of stage cT4 prostate cancer (PC), surgery may also be an appropriate option in selected patients as part of a multimodal approach. The role and the sequence with which to optimize therapy combinations in this setting are still unknown. This mini review summarizes the current evidence for management of cT4 PC. PATIENT SUMMARY: This mini review examines current evidence for the treatment options for locally advanced prostate cancer. The role of surgery in these patients can be considered as part of a combination treatment strategy along with other modalities such as radiotherapy and hormone therapy.
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Neoplasias de la Próstata/terapia , Terapia Combinada , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/patologíaRESUMEN
OBJECTIVE: To evaluate the effect of adding multiparametric magnetic resonance imaging (mpMRI) to pre-surgical planning on surgical decision making for the management of high-risk prostate cancer (HRPC). PATIENTS AND METHODS: A survey was designed to query multiple centers on surgical decisions of 41 consecutive HRPC cases seen from 2012 to 2015. HRPC was defined by the National Comprehensive Cancer Center Network guidelines. Six fellowship-trained urologic oncologists were asked for their surgical plan in regards to the degree of planned nerve-sparing and lymph node dissection. Two rounds of surveys were administered to six external urologic oncologists. The first survey included the case description only and the second included case description with mpMRI images and report. The correct surgical plan was analyzed by correlation of the degree of planned surgical excision and consistency with the final pathologic evaluation. A priori, an effect size of 20% change was used to determine statistical significance, at p < 0.05. RESULTS: All cases had at least one change to surgical planning after mpMRI review. Forty (98%) patients had a change in the degree of planned nerve sparing: wider excision in 32% and increased nerve sparing in 24%. After mpMRI the correct surgical plan change was made in 49% for the right and left 51%, decreasing the potential for positive margins. Lymph node dissection was altered from standard to extended lymph node dissection in 17%. CONCLUSIONS: Although mpMRI is not integrated in guidelines for preoperative planning in HRPC, its use may impact surgical planning, cancer control, and quality of life.
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Imagen por Resonancia Magnética , Cuidados Preoperatorios , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Imágenes de Resonancia Magnética Multiparamétrica , Estadificación de Neoplasias , Pronóstico , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Medición de RiesgoRESUMEN
Importance: The adrenal-restrictive HSD3B1(1245A) allele limits extragonadal dihydrotestosterone synthesis, whereas the adrenal-permissive HSD3B1(1245C) allele augments extragonadal dihydrotestosterone synthesis. Retrospective studies have suggested an association between the adrenal-permissive allele, the frequency of which is highest in white men, and early development of castration-resistant prostate cancer (CRPC). Objective: To examine the association between the adrenal-permissive HSD3B1(1245C) allele and early development of CRPC using prospective data. Design, Setting, and Participants: The E3805 Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a large, multicenter, phase 3 trial of castration with or without docetaxel treatment in men with newly diagnosed metastatic prostate cancer. From July 28, 2006, through December 31, 2012, 790 patients underwent randomization, of whom 527 had available DNA samples. In this study, the HSD3B1 germline genotype was retrospectively determined in 475 white men treated in E3805 CHAARTED, and clinical outcomes were analyzed by genotype. Data analysis was performed from July 28, 2006, to October 17, 2018. Interventions: Men were randomized to castration plus docetaxel, 75 mg/m2, every 3 weeks for 6 cycles or castration alone. Main Outcomes and Measures: Two-year freedom from CRPC and 5-year overall survival, with results stratified by disease volume. Patients were combined across study arms according to genotype to assess the overall outcome associated with genotype. Secondary analyses by treatment arm evaluated whether the docetaxel outcome varied with genotype. Results: Of 475 white men with DNA samples, 270 patients (56.8%) inherited the adrenal-permissive genotype (≥1 HSD3B1[1245C] allele). Mean (SD) age was 63 (8.7) years. Freedom from CRPC at 2 years was diminished in men with low-volume disease with the adrenal-permissive vs adrenal-restrictive genotype: 51.0% (95% CI, 40.9%-61.2%) vs 70.5% (95% CI, 60.0%-80.9%) (P = .01). Overall survival at 5 years was also worse in men with low-volume disease with the adrenal-permissive genotype: 57.5% (95% CI, 47.4%-67.7%) vs 70.8% (95% CI, 60.3%-81.3%) (P = .03). Hazard ratios were 1.89 (95% CI, 1.13-3.14; P = .02) for CRPC and 1.74 (95% CI, 1.01-3.00; P = .045) for death. There was no association between genotype and outcomes in men with high-volume disease. There was no interaction between genotype and benefit from docetaxel. Conclusions and Relevance: Inheritance of the adrenal-permissive HSD3B1 genotype is associated with earlier castration resistance and shorter overall survival in men with low-volume metastatic prostate cancer and may help identify men more likely to benefit from escalated androgen receptor axis inhibition beyond gonadal testosterone suppression.
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Docetaxel/administración & dosificación , Complejos Multienzimáticos/genética , Progesterona Reductasa/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/cirugía , Esteroide Isomerasas/genética , Anciano , Alelos , Antagonistas de Andrógenos/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Retrospective studies in selected patients have demonstrated a survival benefit with prostatectomy or radiotherapy (RT) of the primary tumor in metastatic hormone-sensitive prostate cancer (mHSPC). However, there is currently not enough evidence to recommend RT to the primary tumor as the standard of care for patients treated with androgen deprivation therapy plus abiraterone or docetaxel for low-volume mHSPC.
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Antagonistas de Andrógenos/uso terapéutico , Androstenos/uso terapéutico , Docetaxel/uso terapéutico , Metástasis de la Neoplasia , Prostatectomía/métodos , Neoplasias de la Próstata , Radioterapia/métodos , Antineoplásicos/uso terapéutico , Humanos , Masculino , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/terapia , Estadificación de Neoplasias , Selección de Paciente , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Nivel de Atención , Carga TumoralRESUMEN
INTRODUCTION: Neoadjuvant chemotherapy (NAC) prior to radical or partial cystectomy is considered the standard of care for eligible patients with muscle-invasive urothelial carcinoma. Despite guideline recommendations, adoption of NAC has historically been low, although prior studies have suggested that use is increasing. In this contemporary study, we examine trends in the use of NAC and explore factors associated with its receipt. METHODS: We identified patients in the National Cancer Database who underwent radical or partial cystectomy for cT2-cT4N0M0 urothelial carcinoma from 2006-2014. The proportion of patients receiving NAC during each year was examined. Logistic regression models were used to evaluate clinical and socioeconomic factors associated with the receipt of NAC. RESULTS: A total of 18 188 patients were identified who underwent radical or partial cystectomy for muscle-invasive bladder cancer. Overall, 3940 (21.7%) received NAC. We noted a significant increase in the use of NAC over time, from 9.7% in 2006 to 32.2% in 2014. Factors associated with lower use of NAC include older age, higher comorbidity score, lower cT stage, lower hospital radical cystectomy volume, treatment at a non-academic facility, lower patient income, and receipt of partial cystectomy (all p<0.001). Interestingly, neither sex nor race were associated with receipt of NAC. CONCLUSIONS: Use of NAC has increased significantly over time to a modest rate of 32%. However, disparities still exist in the receipt of NAC, and future efforts aimed at mitigating these disparities are warranted.
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Traditionally, systemic androgen deprivation therapy (ADT) has been the primary treatment modality in metastatic prostate cancer (mPCa) while treatment of the primary tumor has been reserved for patients with clinically localized disease. Emerging data suggests that treating the primary tumor in patients with metastatic disease may provide a survival benefit. However, these studies are fraught with selection bias towards patients with favorable disease characteristics. Despite these limitations, clinicians are becoming increasingly interested in consolidative treatment of the primary tumor in this setting. Many translational models and observational studies of cytoreduction in mPCa have yielded compelling results, suggesting a potential biological and clinical benefit. While there are no published randomized control trials on cytoreduction in mPCa, the literature regarding safety, feasibility, and potential symptomatic benefit of cytoreductive prostatectomy (CRP) in mPCa supports further investigation. Thus, MEDLINE and PubMed electronic databases were queried for English language articles related to patients with mPCa who underwent radical prostatectomy. Keywords used include: cytoreductive prostatectomy, radical prostatectomy, oligometastatic, mPCa, and oligometastasis. In this review we examine the literature regarding the feasibility of CRP as well as the reported oncologic outcomes, limitations of the literature, and future directions. Since there is currently no level one evidence to support its use, CRP should not be applied outside a clinical trial. A better understanding of the biology driving mPCa, in conjunction with standardization of clinical trials, will help expedite actionable data acquisition that may improve clinical outcomes.
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IMPORTANCE: The variant HSD3B1 (1245C) allele enhances dihydrotestosterone synthesis and predicts resistance to androgen-deprivation therapy (ADT) for biochemically recurrent prostate cancer after prostatectomy and for metastatic disease. Whether this is true after radiotherapy is unknown. OBJECTIVE: To determine whether the HSD3B1 (1245C) allele predicts worse clinical outcomes from ADT for biochemical recurrence after radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: The Prostate Clinical Research Information System at Dana-Farber Cancer Institute was used to identify the study cohort, which included men treated with ADT for biochemical recurrence after primary radiotherapy between 1996 and 2013. We retrospectively determined HSD3B1 genotype. MAIN OUTCOMES AND MEASURES: Time to progression, time to metastasis, and overall survival according to genotype. Demographic and treatment characteristics were evaluated for confounders. Multivariable analyses were performed to adjust for known prognostic factors. RESULTS: A total of 218 eligible men were identified, of whom 213 (98%) were successfully genotyped. Of these, 97 of 213 (46%), 96 of 213 (45%) and 20 of 213 (9%) carried 0, 1, and 2 variant alleles. Overall variant allele frequency was 136 of 426 alleles (32%). Median patient age (interquartile range) was 69 (63-74), 72 (65-78), and 69 (65-77) years for 0, 1, and 2 variant alleles (P = .03). Demographic and treatment factors were otherwise similar. During a median follow-up of 7.9 years, median time to progression was 2.3 years (95% CI, 1.6-3.1 years) with 0 variant alleles, 2.3 years (95% CI, 1.5-3.3 years) with 1 variant allele, and 1.4 years (95% CI, 0.7-3.3 years) with 2 variant alleles (P = .68). Median time to metastasis diminished with the number of variant alleles inherited: 7.4 (95% CI, 6.7-9.7), 5.8 (95% CI, 4.9-6.5), and 4.4 (95% CI, 3.0-5.7) years, with inheritance of 0, 1, and 2 variant alleles, respectively (P = .03). Median OS was 7.7 (95% CI, 6.7-10.3), 6.9 (95% CI, 5.8-8.4), and 7.2 (95% CI, 3.8-7.9) years with inheritance of 0, 1, and 2 variant alleles, respectively (P = .31). On multivariable analysis with 0 variant alleles as the reference, the adjusted hazard ratio for metastasis was 1.19 (95% CI, 0.74-1.92) (P = .48) for 1 variant allele and 2.01 (95% CI, 1.02-3.97) (P = .045) for 2 variant alleles. Multivariable analysis did not demonstrate significant differences in TTP or OS. CONCLUSIONS AND RELEVANCE: In this study, the HSD3B1 (1245C) allele was associated with more rapid development of metastases in men treated with ADT for biochemical recurrence after primary radiation therapy for prostate cancer. Notably, 105 of 213 men (49%) had received prior ADT, and 119 of 213 (56%) received an androgen receptor antagonist during salvage treatment, both of which may attenuate the effect of the variant allele.
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Antagonistas de Andrógenos/uso terapéutico , Biomarcadores Farmacológicos , Complejos Multienzimáticos/genética , Recurrencia Local de Neoplasia/genética , Progesterona Reductasa/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Esteroide Isomerasas/genética , Anciano , Alelos , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Quimioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/genética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Ongoing prospective studies are evaluating treatment of the primary tumor in men with de novo metastatic prostate cancer (PCa). One potential benefit is prevention of morbidity from local progression. Thus, local therapy may be best applied selectively to men with local progression once resistance to first-line therapies has occurred. Here, we gather support for the hypothesis that radical prostatectomy (RP) is safe and preserves quality of life (QOL) when applied in men with metastatic castration-resistant PCa (mCRPC). We analyzed 14 patients who underwent RP in the setting of mCRPC from 2008 to 2016. Median time from mCRPC to RP was 5.1 mo (interquartile range [IQR] 1.4-12.0). Median preoperative and <3 mo postoperative Expanded Prostate Cancer Index Composite urinary function QOL scores were 84 (IQR 70-95) and 78 (IQR 62-81), respectively. There were one Clavien Grade III, three Grade II, and one Grade I complications postoperatively. In these patients with mCRPC, RP was feasible with limited minor complications. PATIENT SUMMARY: We report on a select group of men with metastatic castration-resistant prostate cancer who had prostatectomy. Prostatectomy is highly investigational in this setting and should not be used outside of a clinical trial other than for symptom relief.