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Victor Reuter

Publications and source records attributed to Victor Reuter.

At least 19 recordsLinked to original sources
PubMed2006

Treatment outcome for metastatic papillary renal cell carcinoma patients.

BACKGROUND: Most clinical trial reports in metastatic renal cell carcinoma (RCC) do not distinguish between histologic subtypes, making it difficult to assess specific treatment efficacy. The current retrospective study sought to define clinical features and outcome data for metastatic papillary RCC. METHODS: Clinical features, treatment outcome, and survival were evaluated in 38 patients with metastatic papillary RCC who underwent clinical evaluation at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 2005. Twenty-three of 513 individuals were identified from a clinical trial database, 14 of 1895 from a surgery database, and 1 of 357 from a pathology database. A literature review of systemic therapy in metastatic papillary RCC was performed. RESULTS: Among the 38 patients, 30 had been treated at MSKCC with various systemic therapies, including cytokines. Twelve therapies resulted in stable disease, 30 in initial progression of disease, and 1 in an unknown response. One patient had a partial response to sunitinib, a novel multitargeted tyrosine kinase inhibitor. The median overall survival time for the entire study group was 8 months (95% confidence interval, 5-12). A literature review on treatment of metastatic papillary RCC produced 4 reports, confirming a lack of efficacy for systemic therapy. CONCLUSIONS: A resistance to systemic therapy characterizes patients with metastatic papillary RCC. Further understanding of the genetics and molecular biology and subtypes involved may provide the basis for more effective agents. Treatment with targeted therapies or other experimental agents is warranted.

Adult↗
PubMed2006

Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy.

BACKGROUND: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP). METHODS: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS. RESULTS: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS. CONCLUSIONS: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good.

Aged↗
PubMed2006

Persistent prostate-specific antigen expression after neoadjuvant androgen depletion: an early predictor of relapse or incomplete androgen suppression.

OBJECTIVES: To analyze post-androgen depletion (AD) primary tumors to identify markers of treatment failure because AD does not reduce the probability of prostate-specific antigen (PSA) failure after prostatectomy. METHODS: Tumors removed by radical prostatectomy after 3 months of AD from 21 patients were analyzed for gene expression using oligonucleotide arrays. Differences between patients with and without relapse were identified using a conservative significance criteria of a threefold change and delta 0.68, ensuring a false discovery rate of less than 11%. RESULTS: At 50 months of follow-up, 7 of the 18 evaluable patients developed a biochemical recurrence. Gleason grade, pretherapy PSA level, T stage, and margin status were similar between the two groups. Patients with recurrence had greater post-AD PSA levels than those without recurrence (0.87 versus 0.19 ng/mL; P = 0.042). Gene expression analysis revealed 35 probe sets overexpressed in tumors from patients who relapsed. Among the highest ranked probe sets were PSA and other androgen-responsive genes. Serum PSA values during AD revealed similar findings. After 40 days of AD, the PSA level in those without recurrence was 1.21 ng/mL versus 4.5 ng/mL in those with recurrence (P = 0.0034). Immunohistochemistry of post-AD tumors also demonstrated a high PSA staining intensity in many tumors that recurred relative to those that didn't. CONCLUSIONS: The results of our study show that early recurrence is associated with expression of androgen-responsive genes. Surprisingly, these could be identified as early as 3 months after the initiation of AD therapy. Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study.

Androgen Antagonists↗
PubMed2005

Tobacco smoking, GSTP1 polymorphism, and bladder carcinoma.

BACKGROUND: Although cigarette smoking is considered a major risk factor for bladder carcinoma, little is known about the interaction between metabolic genes such as glutathione-S-transferase P1 and tobacco smoking in this process. GSTP1 may play a role in detoxification of tobacco-related carcinogens. METHODS: In this case-control study of 145 cases with bladder carcinoma (male:female = 7.5:1) and 170 noncancer controls (male:female = 3.7:1), the relation between genetic polymorphisms of GSTP1 and susceptibility to bladder carcinoma was investigated and the gene-environment interaction between tobacco smoking and GSTP1 polymorphism was evaluated. Epidemiological data were collected for all cases and controls by a standard questionnaire. Polymorphisms of GSTP1 were measured by polymerase chain reaction-restriction fragment length polymorphism. The logistic regression model in SAS was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Cigarette smoking was confirmed as a risk factor of bladder carcinoma with an OR of 3.1 (95% CI: 1.7-5.9) after controlling for potential confounding factors. The OR for pack-years of smoking as a continuous variable was 2.4 (95% CI: 2.0-2.8). The ORs were 7.6 (95% CI: 1.18-49.51) for isoleucine/valine (Ile/Val) and 6.5 (95% CI: 1.01-41.56) for Ile/Ile when the homozygous Val/Val was considered as comparison group after adjusting for age, gender, race, and education. The adjusted OR for interaction between smoking and the GSTP1 (any Ile genotype) was 11.42 (95% CI: 0.53-248.15). CONCLUSIONS: The results indicate that the Ile 105 allele is associated with an increased risk of bladder carcinoma and suggest that individuals who smoke and possess the Ile allele might be at increased risk for bladder carcinoma.

Alcohol Drinking↗
PubMed2005

A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma.

PURPOSE: Few published studies have simultaneously analyzed multiple prognostic factors to predict recurrence after surgery for conventional clear cell renal cortical carcinomas. We developed and performed external validation of a postoperative nomogram for this purpose. We used a prospectively updated database of more than 1,400 patients treated at a single institution. MATERIALS AND METHODS: From January 1989 to August 2002, 833 nephrectomies (partial and radical) for renal cell carcinoma of conventional clear cell histology performed at Memorial Sloan-Kettering Cancer Center were reviewed from the center's kidney database. Patients with von Hippel-Lindau disease or familial syndromes, as well as patients presenting with synchronous bilateral renal masses, or distant metastases or metastatic regional lymph nodes before or at surgery were excluded from study. We modeled clinicopathological data and disease followup for 701 patients with conventional clear cell renal cell carcinoma. Prognostic variables for the nomogram included pathological stage, Fuhrman grade, tumor size, necrosis, vascular invasion and clinical presentation (ie incidental asymptomatic, locally symptomatic or systemically symptomatic). RESULTS: Disease recurrence was noted in 72 of 701 patients. Those patients without evidence of disease had a median and maximum followup of 32 and 120 months, respectively. The 5-year probability of freedom from recurrence for the patient cohort was 80.9% (95% confidence interval 75.7% to 85.1%). A nomogram was designed based on a Cox proportional hazards regression model. Following external validation predictions by the nomogram appeared accurate and discriminating, and the concordance index was 0.82. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of freedom from recurrence for patients with conventional clear cell renal cell carcinoma. This nomogram may be useful for patient counseling, clinical trial design and effective patient followup strategies.

Carcinoma, Renal Cell↗
PubMed2004

Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma.

PURPOSE: To describe survival in previously treated patients with metastatic renal cell carcinoma (RCC) who are candidates for clinical trials of new agents as second-line therapy. PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 251 patients with advanced RCC treated during 29 consecutive clinical trials between 1975 and 2002. Clinical features were first examined in univariate analyses, and then a stepwise modeling approach based on Cox regression was used to form a multivariate model. RESULTS: Median survival for the 251 patients was 10.2 months and differed according to year of treatment, with patients treated after 1990 showing longer survival. In this group, the median overall survival time was 12.7 months. Because the purpose of this analysis was to establish prognostic factors for present-day clinical trial design, prognostic factor analysis was performed on these patients. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status, low hemoglobin level, and high corrected serum calcium. These were used as risk factors to categorize patients into three different groups. The median time to death in patients with zero risk factors was 22 months. The median survival in patients with one of these prognostic factors was 11.9 months. Patients with two or three risk factors had a median survival of 5.4 months. CONCLUSION: Treatment with novel agents during a clinical trial is indicated for patients with metastatic RCC after progression to cytokine treatment. Three prognostic factors for predicting survival were used to categorize patients into risk groups. These risk categories can be used in clinical trial design and interpretation.

Adolescent↗
PubMed2004

Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance.

The androgen-signaling pathway is critical to the development and progression of prostate cancer and androgen ablation is a mainstay of therapy for this disease. We performed a genome-wide expression analysis of human prostate cancer during androgen ablation therapy to identify genes regulated by androgen and genes differentially expressed after the development of resistance. Six hundred and fifty-four of 63,175 probe sets detected significant expression changes after 3 months of treatment with goserelin and flutamide. This included 149 genes that were also differentially expressed 36 hours after androgen withdrawal in LNCaP cells. These genes reflect the physiological changes that occur in treated tumors and include potential direct targets of the androgen receptor. Expression profiles of androgen ablation-resistant tumors demonstrated that many of the gene expression changes detected during therapy were no longer present suggesting a reactivation of the androgen response pathway in the absence of exogenous hormone. Therapy resistance was associated with differential expression of a unique set of genes that reflect potential mechanisms of reactivation. Specifically an up-regulation of the androgen receptor and key enzymes for steroid biosynthesis suggest that resistant tumors have increased sensitivity to and endogenous synthesis of androgenic hormones. The specific pathways of reactivation provide opportunities for classification of resistant tumors and targeted therapies.

Algorithms↗
PubMed2004

Is year of radical prostatectomy a predictor of outcome in prostate cancer?

PURPOSE: We examined whether the year in which radical prostatectomy (RP) was performed is a predictor of treatment outcome after controlling for standard prognostic factors. MATERIALS AND METHODS: We examined the association between RP year and outcome in 6,556 patients from 7 centers using preoperative and pathological features. Patients underwent surgery between 1985 and 2000. The variables analyzed were RP year, clinical stage, pretreatment prostate specific antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant hormones and adjuvant therapy. Median followup was 23 months (maximum 166). Separate Cox multivariate regression analyses were performed to analyze preoperative and postoperative factors. RESULTS: RP year was a predictor of outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p = 0.130). Patient outcome steadily improved with surgery through the mid 1990s and then it appeared to level off. CONCLUSIONS: When controlling for preoperative features, the year in which RP was performed is a predictor of outcome on multivariate analysis. This effect could not be explained by stage migration.

Adult↗
PubMed2003

Cluster analysis of p53 and Ki67 expression, apoptosis, alpha-fetoprotein, and human chorionic gonadotrophin indicates a favorable prognostic subgroup within the embryonal carcinoma germ cell tumor.

PURPOSE: The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT). PATIENTS AND METHODS: These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns. RESULTS: One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P =.005) and cluster affiliation (P =.04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively. CONCLUSION: These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.

Apoptosis↗
PubMed2003

Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens.

PURPOSE: Cancer at the resection margin (a positive surgical margin) after radical prostatectomy is associated with an increased risk of recurrence even after adjusting for other known risk factors, including pretreatment serum prostate specific antigen (PSA), clinical stage, grade and pathological stage (level of extracapsular extension, seminal vesicle invasion and pelvic lymph node status). Of these prognostic factors only surgical margin status can be influenced by surgical technique. We examined variations in the rate of positive surgical margins among surgeons after controlling for the severity of disease and volume of cases per surgeon. MATERIALS AND METHODS: A total of 4,629 men were treated with radical prostatectomy by 1 of 44 surgeons at 2 large urban centers between 1983 and 2002 for clinical stage T1-T3NxM0 prostate cancer. Patients were excluded if they had previously received androgen deprivation therapy or radiation therapy to the pelvis. Positive surgical margins were defined as cancer at the inked resection margin. Other risk factors analyzed were serum PSA, grade (Gleason sum), extracapsular extension level (none, invasion into the capsule, present [not otherwise specified], focal extracapsular extension or established extracapsular extension), seminal vesicle invasion, pelvic lymph node metastases, surgery date, surgeon and volume of cases per surgeon. RESULTS: For the 26 surgeons who each treated more than 10 patients in the study the rate of positive surgical margins was 10% to 48%. On multivariable analysis higher serum PSA, extracapsular extension level, higher radical prostatectomy Gleason sum, surgery date, surgical volume and surgeon were associated with surgical margin status after controlling for all other clinical and pathological variables. CONCLUSIONS: While the clinical and pathological features of cancer are associated with the risk of a positive margin in radical prostatectomy specimens, the technique used by individual surgeons is also a factor. Lower rates of positive surgical margins for high volume surgeons suggest that experience and careful attention to surgical details, adjusted for the characteristics of the cancer being treated, can decrease positive surgical margin rates and improve cancer control with radical prostatectomy.

Clinical Competence↗
PubMed2003

A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer.

PURPOSE: We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases. RESULTS: Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes. CONCLUSIONS: Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

Adult↗
PubMed2002

Genomic and expression analysis of the 12p11-p12 amplicon using EST arrays identifies two novel amplified and overexpressed genes.

We performed parallel array comparative genomic hybridization and array expression analysis of the 12p11-p12 amplicon in human testicular seminomas and an ovarian carcinoma cell line using an expressed sequence tags (ESTs) array spotted with 8254 ESTs. The data were normalized using a robust statistical modeling and the significance inferred from the local SD. We identified two ESTs within the chromosomal amplicon that were amplified and overexpressed in > or =75-100 percent of analyzed tumors with the 12p11-p12 amplicon. These sequences, belonging to coding regions of two novel genes designated here as GCT1 and GCT2, were broadly expressed in a panel of human tissues, including testis and ovary. GCT1 and GCT2 were overexpressed in 92 and 71 percent, respectively, of a panel of seminomas tested. Combined array comparative genomic hybridization and array expression analysis is a valid approach for gene discovery in large chromosomal amplicons.

Aged↗
PubMed2002

Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease.

The identification of genes that contribute to the biological basis for clinical heterogeneity and progression of prostate cancer is critical to accurate classification and appropriate therapy. We performed a comprehensive gene expression analysis of prostate cancer using oligonucleotide arrays with 63,175 probe sets to identify genes and expressed sequences with strong and uniform differential expression between nonrecurrent primary prostate cancers and metastatic prostate cancers. The mean expression value for >3,000 tumor-intrinsic genes differed by at least 3-fold between the two groups. This includes many novel ESTs not previously implicated in prostate cancer progression. Many differentially expressed genes participate in biological processes that may contribute to the clinical phenotype. One example was a strong correlation between high proliferation rates in metastatic cancers and overexpression of genes that participate in cell cycle regulation, DNA replication, and DNA repair. Other functional categories of differentially expressed genes included transcriptional regulation, signaling, signal transduction, cell structure, and motility. These differentially expressed genes reflect critical cellular activities that contribute to clinical heterogeneity and provide diagnostic and therapeutic targets.

Adult↗
PubMed2002

Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology.

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non-clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non-clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non-clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.

Adolescent↗
PubMed2002

Salvage chemotherapy for patients with advanced pure seminoma.

PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment. PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem-cell rescue. RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease. CONCLUSION: Most patients with advanced seminoma are cured with standard first-line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease.

Adult↗
PubMed2002

Partial nephrectomy: the rationale for expanding the indications.

BACKGROUND: We report preliminary results of partial nephrectomy for renal tumors of > or =4 cm in 39 patients with the intent of extending the indications for kidney-sparing surgery. METHODS: From July 1989 to October 2001, 39 patients underwent a partial nephrectomy for renal cortical tumors >4 cm in maximum diameter. Fourteen (36%) had the procedure performed for essential reasons, and 25 (64%) had an elective kidney-sparing operation. We evaluated tumor location and histology, perioperative renal function, and postoperative complications. RESULTS: There were 20 conventional clear-cell (51%), 13 papillary (33%), 4 chromophobe (10%), and 3 oncocytomas (8%) with a median tumor size of 5 cm. After a median follow-up of 13 months, 36 patients had no evidence of disease, 1 patient had died as a result of other causes, and 2 patients who had essential operations were alive with disease. Twenty-three patients (70%) maintained normal postoperative renal function. Of six patients with moderate preoperative renal dysfunction, five (83%) had no change in postoperative renal function and only one patient required short-term dialysis. CONCLUSIONS: With careful patient selection, partial nephrectomy can be effectively used to treat patients with renal cortical tumors >4 cm in diameter. The benefits of this approach include the effective local tumor control while at the same time preserving maximum renal function.

Adult↗
PubMed2002

Cytotoxic treatment of aggressive prostate tumors with or without neuroendocrine elements.

The aim of this study was to investigate whether there is an association between the presence of neuroendocrine elements in relapsed prostate cancer and sensitivity to estramustine/etoposide and carboplatin or cisplatin. Thirty patients with progressive metastatic castrate prostate cancer were selected on the basis of clinical criteria for treatment with cytotoxic chemotherapy. The criteria included a tumor biopsy specimen taken during relapse showing neuroendocrine features based on morphology alone (carcinoid elements, small cell tumor) or by immunohistochemistry (detection of chromogranin A, neuron-specific enolase or synaptophysin). Patients were treated with cis- or carboplatin, estramustine (orally) and etoposide (orally or intravenously). Remission of radiographically visualized lesions, decline of prostate-specific antigen (PSA) or death owing to any cause constituted (separately reported) the endpoints. Tumor remission was found in about half of the patients, determined either by changes in measurable lesions or by a 50% decline in serum PSA. Neuroendocrine elements--irrespective of how they were identified--were not predictive of tumor remission or survival. Regression of measurable lesions by > 50% was seen in 4/9 (44%) cases of small cell carcinoma, 6/13 (46%) of poorly differentiated carcinoma, 7/13 (54%) of tumors with one marker immunohistochemically detected and 3/7 (43%) of tumors without any staining. It is concluded that response to chemotherapy was not predicted solely on the basis of the presence or absence of neuroendocrine elements in a relapsed tumor specimen. The results support the use of cytotoxic drugs in the relapsed setting and definitive trials are ongoing to prove any benefit to survival.

Aged↗