RESUMO
To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 µg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 µg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 µg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.
Assuntos
Exame Retal Digital , Detecção Precoce de Câncer/métodos , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Detecção Precoce de Câncer/normas , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , UltrassonografiaRESUMO
UNLABELLED: Better intraprostatic cancer imaging techniques are needed to guide clinicians in prostate cancer treatment decisions. Because many genes are specifically overexpressed in cancer cells, one strategy to improve prostate cancer detection is to image intraprostatic cancer-specific transcriptional activity. Because of the obstacles of weak cancer- or tissue-specific promoter activity and bladder clearance of many PET tracers, intraprostatic PET of gene transcriptional activity has not been previously reported. METHODS: The two-step transcriptional amplification (TSTA) system that amplifies the prostate-specific antigen promoter activity was used for PET imaging of the reporter gene herpes simplex virus type-1 sr39 thymidine kinase (HSV1-sr39tk). The TSTA-sr39tk system was injected directly into prostates or prostatic tumors as a replication-incompetent adenovirus (AdTSTA-sr39tk) and imaged using PET. RESULTS: AdTSTA-sr39tk was able to image prostate-specific antigen promoter transcriptional activity by 9-(4-(18)F-fluoro-3-[hydroxymethyl]butyl)guanine PET, in both mouse and canine prostates in vivo. Ex vivo small-animal PET images, scintigraphic counts, and sr39tk expression analysis confirmed the specificity of the observed signal. CONCLUSION: Here, by combining the TSTA-amplified signal with a protocol for tracer administration, we show that in vivo PET detection of transcriptional activity is possible in both mouse and immunocompetent canine prostates. These results suggest that imaging applications using transcription-based tumor-specific promoters should be pursued to better visualize cancer foci that escape detection by conventional biopsies.
Assuntos
Tomografia por Emissão de Pósitrons , Próstata/metabolismo , Transcrição Gênica , Adenoviridae/genética , Animais , Cães , Estudos de Viabilidade , Genes Reporter/genética , Células HEK293 , Herpesvirus Humano 1/enzimologia , Humanos , Imunocompetência/genética , Masculino , Camundongos , Estadiamento de Neoplasias , Especificidade de Órgãos , Regiões Promotoras Genéticas/genética , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Timidina Quinase/genéticaRESUMO
At present, immunotherapy in urological malignancy is experiencing a renaissance, particularly with the emergence of a host of innovative cancer vaccines. Herein, we will review promising immunotherapeutic approaches and evaluate the data supporting their inclusion in novel combination strategies.
Assuntos
Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/terapia , Vacinas Anticâncer , HumanosRESUMO
Immune-sensitive urologic malignancies include prostate, kidney and bladder cancers. To date, most immunotherapeutic treatments have been applied to advanced metastatic disease. Limited efficacy in this setting is likely due to an excessive disease burden, which overwhelms the capacity of the immune system. Immunotherapy has not been widely utilized in a low-disease-burden state - a setting in which the immune system may be best suited to effectively mount a clinically meaningful response. The emergence of high-intensity focused ultrasound, and more recently, low-intensity focused ultrasound technologies, have demonstrated not only immune-stimulatory effects but also an interesting capacity to alter tissue architecture and cell membrane properties, which may be exploited to increase tumoral uptake of drugs and vaccines. In this article, we review the literature supporting the novel use of ultrasound combination therapy with adjunctive agents in the treatment of urologic malignancy.
Assuntos
Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Neoplasias Urológicas/diagnóstico por imagem , Neoplasias Urológicas/terapia , Terapia Combinada , Humanos , Imunoterapia/métodos , Terapia por Ultrassom/métodos , Ultrassonografia , Neoplasias Urológicas/imunologiaRESUMO
BACKGROUND: The management of renal cell carcinoma (RCC) is evolving toward less extirpative surgery and the use of targeted therapy. The authors set out to provide a benchmark against which emerging therapies should be measured. METHODS: A prospective database including clinical and pathological variables for 1632 patients with RCC treated between 1989 and 2005 was queried. Patients were stratified using the University of California-Los Angeles Integrated Staging System (UISS) into low-, intermediate-, and high-risk groups. Disease-specific survival (DSS) was measured. Response to systemic therapy for patients with advanced disease was assessed. RESULTS: Nephrectomy was performed in 1492 patients. Overall 5-, 10-, and 15-year DSS was 55%, 40%, and 29%. For localized disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 97% and 92%, 81% and 61%, and 62% and 41%, respectively. For metastatic disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 41% and 31%, 18% and 7%, and 8% and 0%, respectively. Patients with metastatic disease receiving immunotherapy (n=453) had complete response in 7% (median survival [MS], 120+ months), partial response in 15% (MS, 42.8 months), stable disease in 33% (MS, 38.6 months), and progressive disease in 45% (MS, 11.6 months). CONCLUSIONS: Most patients with localized RCC do well with surgery alone, but effective adjuvant therapy is needed for patients identified as at high risk for recurrence. For advanced disease, newer targeted and potentially less toxic treatments should be at least as effective as those achieved with aggressive surgical resection and immunotherapy.
Assuntos
Benchmarking/estatística & dados numéricos , Imunoterapia , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Carcinoma Papilar/mortalidade , Carcinoma Papilar/secundário , Carcinoma Papilar/terapia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Criança , Terapia Combinada , Feminino , Humanos , Neoplasias Renais/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: Na,K-adenosine triphosphatase, which is composed of a catalytic alpha-subunit and a regulatory beta-subunit, generates an electrochemical gradient across the plasma membrane. Previous studies demonstrated altered Na,K-adenosine triphosphatase subunit expression in renal clear cell carcinoma and an association of subunit levels with the prediction of recurrent bladder cancer. We determined the clinical association of protein expression patterns of the Na,K-adenosine triphosphatase alpha1 and beta1-subunits in renal clear cell carcinoma using tissue microarrays with linked clinicopathological data. MATERIALS AND METHODS: The UCLA kidney cancer tissue microarray was used to investigate the protein expression of Na,K-adenosine triphosphatase alpha1 and beta1-subunits by immunohistochemistry in 342 patients with renal clear cell carcinoma who were treated with radical nephrectomy. Of these patients clinical outcomes studies were performed in 317. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: We found that the alpha1-subunit was a significant and independent predictor of disease specific death from renal clear cell carcinoma on multivariate Cox proportional hazards analysis that included established prognostic factors Eastern Cooperative Oncology Group performance status, pT status, metastasis status and tumor grade. Significance was found when examining all patients with clear cell renal cell carcinoma as well as patient substrata with low or high grade tumors and localized or metastatic disease, suggesting that the Na,K-adenosine triphosphatase alpha1-subunit could be used as a new prognosticator for disease specific death from renal clear cell carcinoma. CONCLUSIONS: These results suggest that Na,K-adenosine triphosphatase alpha1-subunit expression patterns may be a useful clinical prognosticator for renal clear cell carcinoma. The Na,K-adenosine triphosphatase beta1-subunit was not found to be a useful prognosticator in this setting.
Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/enzimologia , Neoplasias Renais/mortalidade , ATPase Trocadora de Sódio-Potássio/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de SobrevidaAssuntos
Oncologia , Sociedades Médicas , Neoplasias Urológicas , Feminino , Neoplasias dos Genitais Femininos , HumanosRESUMO
Monitoring the spontaneous antibody (Ab) response against a panel of relevant tumor-associated antigens (TAA) in cancer patients may provide useful information regarding the clinical status of cancer. However, current Ab detection approaches require the purification of recombinant proteins, which is often difficult to achieve. In order to bypass the purification of recombinant proteins, we identified a dominant B-cell epitope from a shared tumor antigen NY-ESO-1. A synthetic peptide of the epitope, ESO:1-40, was as sensitive as the recombinant protein for detecting Ab against NY-ESO-1 in most patients. NY-ESO-1 specific Ab present in the sera of patients with melanoma, prostate cancer, nonsmall cell lung cancer, esophageal cancer, gastric cancer and hepatocellular carcinoma reacted with the dominant peptide at a similar frequency as the recombinant protein. To our knowledge, ESO:1-40 is the first peptide epitope recognized by sera from a wide spectrum of cancer patients but not healthy donors. This simple and straightforward approach may allow the investigation of the clinical significance of spontaneous Ab responses against multiple TAA and their correlation with the clinical course of malignant diseases in the future.
Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos B/imunologia , Epitopos/análise , Melanoma/imunologia , Proteínas de Membrana/imunologia , Neoplasias/imunologia , Sequência de Aminoácidos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Biomarcadores/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Primers do DNA , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Melanoma/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The enzyme glutathione S-transferase P1 (GSTP1) detoxifies carcinogenic products of tobacco smoke. This exploratory case-control study evaluates the possible effect modification by the GSTP1 Ile105Val polymorphism (replacement of isoleucine by valine at codon 105) on smoking and prostate cancer. Because the Val variant possesses up to a five-fold greater enzymatic activity towards the carcinogenic metabolites of tobacco smoke, the Ile allele is expected to be related to an increase in the risk of prostate cancer among smokers. GSTP1 genotype and epidemiological data were obtained from 122 cases of prostate cancer and 135 healthy males as controls. A logistic regression model was used to estimate odds ratios and 95% confidence intervals. The adjusted OR of homozygous Ile compared to other genotypes for prostate cancer was 1.21 (95% CI: 0.61-2.83). Smoking was not significantly associated with prostate cancer with an adjusted OR of 1.56 (95% CI: 0.78-3.12). However, among individuals with the Ile/Ile genotype, smoking was strongly associated with an increased risk of prostate cancer with an adjusted odds ratio of 4.09 (95% CI: 1.25-13.35). A potential multiplicative interaction was suggested between GSTP1 and smoking on the risk of prostate cancer with the adjusted OR for the interaction of 4.52 (95% CI: 1.07-19.17). To our knowledge, this is the first time that a potential effect modification by the GSTP1 Ile/Ile genotype on smoking and the risk of prostate cancer is suggested.
Assuntos
Glutationa Transferase/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Fumar , Adulto , Substituição de Aminoácidos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Neoplasias da Próstata/enzimologia , Fatores de Risco , Fatores SocioeconômicosRESUMO
PURPOSE: We determined clinical and pathological predictors of positive bone scans and computerized tomography (CT) in patients with biochemical recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: A retrospective analysis of patients treated with RP at West Los Angeles Veterans Affairs Medical Center and University of California-Los Angeles Medical Center was performed to identify men with biochemical recurrence. All postoperative bone scans and pelvic CT following recurrence and prior to the initiation of hormone ablation therapy were reviewed. Preoperative clinical variables, pathological findings, serum prostate specific antigen (PSA) at postoperative imaging and postoperative PSA doubling time were compared between patients with positive and negative imaging study results. RESULTS: A total of 128 patients with biochemical recurrence after RP who had postoperative pelvic CT or bone scans available were identified. A total of 97 bone scans were obtained, of which 11 (11%) were positive, and 71 CT scans were obtained, of which 5 (7%) were positive. Men with PSA doubling time less than 6 months were at increased risk of a positive bone scan (26% vs 3%) or positive CT (24% vs 0%) relative to men with longer PSA doubling time. In men with PSA doubling time less than 6 months the risk of a positive study highly depended on PSA at the time of imaging. In men with PSA less than 10 ng/ml the incidence of a positive study was 0% for pelvic CT and 11% for bone scan. In men with PSA greater than 10 ng/ml the risk of a positive study was 57% for pelvic CT and 46% for bone scan. In men with PSA doubling time greater than 6 months no clear relationship to PSA was seen, although the number of patients with a positive study was extremely low (positive bone scans 3% and positive CT 0%). However, none of the 6 imaging studies performed in men with PSA doubling times greater than 6 months and a markedly elevated PSA of 20 to 90 ng/ml was positive. CONCLUSIONS: The risk of detecting metastatic disease by bone scan or pelvic CT in men with biochemical recurrence following RP with PSA doubling time greater than 6 months is low despite marked PSA increases up to 90 ng/ml. In men with PSA doubling time less than 6 months the risk of detecting metastatic disease markedly increases when PSA is greater than 10 ng/ml. These results have important implications for the timing of imaging in patients with biochemical recurrence following RP.
Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Falha de TratamentoRESUMO
The development of prostatic intraepithelial neoplasia (PIN)-like lesions in the prostate-specific retinoid X receptor-alpha (RXRalpha) null mouse suggests that RXRalpha may protect against neoplasia. The purpose of this study was to characterize RXRalpha protein expression in human prostate to determine if RXRalpha is altered in early stages of tumor progression. Immunohistochemistry with anti-RXRalpha antibody was performed on 138 fresh frozen prostate specimens collected from 27 noncarcinomatous prostates and 111 radical prostatectomy samples of prostate adenocarcinoma (CA). The RXRalpha signal intensity was scored using a scale of 0-3. In normal glands, RXRalpha was expressed strongly in basal cells and only weakly in secretory epithelial cells. This finding was confirmed by double immunofluorescence labeling of RXRalpha and Keratin-903, a basal cell marker, followed by confocal microscopic examination. In basal cells, a gradual decrease of RXRalpha expression was noted from normal glands of noncarcinomatous prostate (3.0 +/- 0) to "normal" glands distant to CA (2.13 +/- 0.44) to "normal" glands adjacent to CA (1.25 +/- 0.53) and high-grade PIN (0.56 +/- 0.58). While nearly all "normal" glands from 138 specimens were positive for RXRalpha in basal cells, only 48% (13 of 27) of the high-grade PIN glands appeared positive. Moreover, basal cell expression of RXRalpha in "normal" tissue was less in specimens with poorly differentiated tumor (Gleason score >/= 8; 1.83 +/- 0.36) compared with well-differentiated tumor (Gleason score < 6; 2.35 +/- 0.34; P = 0.04). Thus, a decrease of RXRalpha in the basal cells may serve as a marker for prostate CA-associated field change, which may represent an early event in the prostate carcinogenic process. These findings suggest that chemoprevention strategies with retinoids may be most effective if applied during the early stages of transformation.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/fisiopatologia , Transformação Celular Neoplásica , Regulação Neoplásica da Expressão Gênica , Estadiamento de Neoplasias , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/fisiopatologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia , Receptores do Ácido Retinoico/biossíntese , Idoso , Diferenciação Celular , Quimioprevenção , Progressão da Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares , Prostatectomia , Receptores Citoplasmáticos e Nucleares , TransativadoresRESUMO
PURPOSE: We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus. MATERIALS AND METHODS: A total of 207 patients with unilateral renal cell carcinoma and tumor thrombus into the renal vein (107) and inferior vena cava (100) who underwent nephrectomy and thrombectomy were compared with 607 without tumor thrombus. RESULTS: At diagnosis 77 patients (37%) had N0M0 disease and 130 (63%) had lymph node (N+) or distant (M1) metastases. Compared with nontumor thrombus cases tumor thrombus was associated with more advanced stage, N+ (26% versus 12%), M1 (54% versus 31%) disease, higher grade and Eastern Cooperative Oncology Group performance status. In N0M0 cases with inferior vena caval tumor thrombus capsular penetration, collecting system invasion and extension into the hepatic vein were more important prognostic variables then the level of inferior vena caval thrombus. In patients with confined N0M0 tumors mean 2 and 5-year survival +/- SD was 83% +/- 8.8% and 72% +/- 10.7% in those with inferior vena caval tumor thrombus, and 90% +/- 9.4% and 68% +/- 16.1% in those with renal vein tumor thrombus, similar to the 93.4% +/- 1.7% and 81 +/- 3.1% rates, respectively, in those without thrombus who had no recurrence within 6 months after nephrectomy. Of patients with M1 disease in whom cytoreductive surgery was done those with and without thrombus showed a similar response to immunotherapy. When there was inferior vena caval and renal vein thrombus, mean 2-year survival was higher after nephrectomy and immunotherapy than after nephrectomy alone (41% +/- 9% and 52% +/- 7% versus 32% +/- 13% and 45% +/- 7%), immunotherapy alone (0% and 13% +/- 12%, respectively) and no treatment (0%). CONCLUSIONS: Renal cell carcinoma with tumor thrombus is associated with worse characteristics. Local tumor extension has greater prognostic importance than the level of inferior vena caval tumor thrombus. Survival is fair in patients with truly confined N0M0 disease and thrombus. The combination of surgery and immunotherapy has a role in thrombus cases. Our data provide the rationale for a prospective study of adjuvant immunotherapy after surgery in N0M0 cases with extensive tumor thrombus.
Assuntos
Carcinoma de Células Renais/patologia , Imunoterapia , Neoplasias Renais/patologia , Células Neoplásicas Circulantes , Nefrectomia , Veias Renais/patologia , Veia Cava Inferior/patologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Veias Hepáticas/patologia , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , TrombectomiaRESUMO
The potential benefits of a lymph node dissection (LND) include more accurate staging, decreased local recurrence rates, and improved survival. However, only limited data support the potential benefits of routine, extensive LND for renal cell carcinoma (RCC). Because of lack of data, no clear practice standard has been established about whether to perform LND and, if so, to what extent. The value of LND for RCC is only relevant if the pattern of lymphatic spread is predictable, which it is not. However, although little evidence supports the value of LND for RCC, it is probable that an occasional patient will have very early metastasis confined to the area of the primary and secondary major lymphatic flow medially and perhaps will benefit therapeutically. In this case, a limited LND is supportable. No information currently available strongly supports the value of a more extensive and potentially more morbid LND for either staging or therapeutic value. Extensive investigation is necessary in order to establish LND as a standard component of RCC surgery.
RESUMO
PURPOSE: To create a comprehensive algorithm that can predict postoperative renal cell carcinoma (RCC) patient outcomes and response to therapy. PATIENTS AND METHODS: A prospective cohort study was performed with outcome assessment on the basis of chart review of 814 patients who underwent nephrectomy between 1989 and 2000. At diagnosis, M1 or N1/N2M0 metastatic disease (M) was present in 346 patients (43%), whereas 468 patients had no metastatic disease (NM) (N0M0). On the basis of UCLA Integrated Staging System category and the presence of metastases, patients were divided into low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups. Decision boxes integrating tumor-node-metastasis staging, tumor grade, and performance status were compiled for determining a patient's risk group. RESULTS: NM-LR patients had 91% disease-specific survival at 5 years, lower recurrence rate, and better disease-free survival compared with NM-IR and HR patients. Disease progressed in 50% of NM-HR patients. Disease-specific survival of NM-HR patients who received immunotherapy (IMT) for recurrent disease was similar to that of M-LR patients treated with cytoreductive nephrectomy and adjuvant IMT. Time from recurrence to death for NM-HR patients was inferior to that for M-LR patients. After IMT, approximately 25% of M-LR and 12% of M-IR patients had long-term progression-free survival. M-HR patients did poorly despite IMT. CONCLUSION: Stratifying RCC patients into high-, intermediate-, and low-risk subgroups provides a clinically useful system for predicting outcome and provides a unique tool for risk assignment and outcome analysis. Subclassifying RCC into well-defined risk groups should allow better patient counseling and identification of both NM-HR subgroups that need adjuvant treatment and nonresponders who need alternative therapies.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia , Algoritmos , Intervalo Livre de Doença , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Falha de Tratamento , Resultado do TratamentoRESUMO
PURPOSE: Previous studies have suggested that prostate specific antigen (PSA) density is a significant independent predictor of biochemical failure after primary therapy. We determined whether pathological PSA density using surgical weight of the radical prostatectomy specimen was an independent predictor of adverse pathological features or biochemical recurrence after radical prostatectomy. We also examined whether combining pathological PSA density with biopsy Gleason score improved risk stratification compared with serum PSA and biopsy Gleason score for predicting PSA recurrence after prostatectomy. MATERIALS AND METHODS: Multivariate analysis was used to determine whether pathological PSA density was an independent predictor of adverse pathology or PSA recurrence after radical prostatectomy in 325 patients treated at a Veterans Affairs medical center. Cutoff points of pathological PSA density were generated to identify patients at various risks for biochemical recurrence. These cutoffs were combined with biopsy Gleason cutoff points 2 to 6, 7 and 8 to 10 to generate a risk stratification system that was compared with a previous risk stratification system using PSA and biopsy Gleason score cutoff points. The validity of the risk stratification system using pathological PSA density and biopsy Gleason score was evaluated in another cohort of 490 patients treated with radical prostatectomy at a tertiary care medical center. RESULTS: Pathological PSA density was an independent predictor of positive surgical margins (p <0.001), nonorgan confined disease (p <0.001), seminal vesicle invasion (p = 0.003) and biochemical recurrence after radical prostatectomy (p <0.001). The cutoff points for pathological PSA density of less than 0.3, 0.3 to 0.7 and greater than 0.7 ng./ml./gm. separated patients into 3 distinct groups at increasing risk for biochemical failure after radical prostatectomy (p <0.001). Pathological PSA density cutoffs combined with biopsy Gleason score cutoffs 2 to 6, 7 and 8 to 10 provided better risk stratification for biochemical failure than cutoffs based on a combination of PSA and biopsy Gleason score in patients treated at the Veterans Affairs (hazards ratio 3.04, confidence interval 2.25 to 4.11, p <0.001) and tertiary care (hazards ratio 2.38, confidence interval 1.78 to 3.18, p <0.001) medical centers. CONCLUSIONS: Pathological PSA density was a strong predictor of advanced pathology and biochemical failure after radical prostatectomy. Pathological PSA density combined with biopsy Gleason score defined a novel risk group system that improved risk stratification compared with a combination of PSA and biopsy Gleason score. These results were validated in another cohort of patients treated with radical prostatectomy at a tertiary care medical center. Further studies are required using PSA density values calculated from preoperative transrectal ultrasound measurements to determine whether a combination of PSA density and biopsy Gleason score provides significant pretreatment risk stratification.
Assuntos
Biomarcadores Tumorais/sangue , Recidiva Local de Neoplasia/diagnóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata , Neoplasias da Próstata/cirurgia , Idoso , Biópsia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Risco , Taxa de SobrevidaRESUMO
PURPOSE: To develop a multivariate model and mathematical formula capable of calculating personalized survival for renal cell carcinoma (RCC) patients with clinically available variables. PATIENTS AND METHODS: A total of 477 patients out of 661 undergoing nephrectomy at the University of California Los Angeles between 1989 and 1999 were eligible for evaluation and formed the analyzed cohort for this retrospective study. Time to death was the primary end point assessed. Univariate analysis for 14 to 20 variables was conducted, followed by a multivariate Cox analysis. The variables that provided independent information as to the time of death for metastatic and nonmetastatic patients were coded and incorporated into a function based on the Nadas equation principle. RESULTS: For nonmetastatic patients, the significant variables in the multivariate analysis were Fuhrman's grade and Eastern Cooperative Oncology Group performance status. For the metastatic patients, Fuhrman's grade, 1997 classification T stage, number of symptoms, nodal involvement, and immunotherapy were independent predictors for survival. These variables, based on the Cox multivariate regression model, were implanted into an exponential Nadas equation. The expected survival predicted by use of the Nadas equations faithfully describes the actual survival based on Kaplan-Meier curves. CONCLUSION: We have developed mathematical equations for estimating survival after radical nephrectomy for RCC. The resulting formulas are capable of better tailoring survival estimates for a specific patient and are based on widely accepted clinical prognostic variables. On validation with external data, this type of representation can be used as a tool for the determination of personalized prognosis and may be useful for patient education and counseling.
Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Modelos Teóricos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Matemática , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Estudos RetrospectivosRESUMO
A prospective clinical trial of prostate cancer screening was conducted at 6 university centers including 6,630 men 50 years old or older who underwent a serum prostate specific antigen (PSA) determination and digital rectal examination. Biopsies were performed if the PSA level was greater than 4.0 ng./ml. (Hybritech Tandem assay) or digital rectal examination was suspicious for cancer. We evaluated the effect on biopsy rate and cancer detection if the cutoff value was shifted from 4.0 to age-specific reference ranges recommended in the literature. In men 50 to 59 years old with normal digital rectal examination findings a decrease from 4.0 to 3.5 ng./ml. would have resulted in a 45% increase in the number of biopsies (39 of 87) and a projected 15% increase in cancer detection. An increase from 4.0 to 4.5 ng./ml. in men 60 to 69 years old would result in 15% fewer biopsies (35 of 238) and would miss 8% of the organ confined tumors (2 of 25). Increasing the cutoff to 6.5 ng./ml. in men 70 years old or older would result in 44% fewer biopsies (70 of 159) and would miss 47% of the organ confined cancers (7 of 15). The number of biopsies performed for each cancer detected with a PSA level of greater than 4.0 ng./ml. remains constant across age groupings, which suggests that the cutoff of 4.0 ng./ml. does not need to be altered in the older men, since it is apparently unaffected by the simultaneously increasing prevalence of benign prostatic hyperplasia and cancer with age. We conclude that a serum PSA concentration of 4.0 ng./ml. should be used as a general guideline for biopsy in all age groups.