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Background: Vertebrates have special structures at the ends of their chromosomes, known as telomeres, which may provide the chromosomes with stability and protect them from exonucleolytic degradation. The shortening of telomeric DNA with each cell division may lead to cell cycle arrest and/or apoptosis of a normal human somatic cell. Telomerase, an RNA-dependent DNA polymerase, elongates the 3'-ends of telomeric DNA. Thus, the presence of telomerase activity may reflect a cell's potential immortal state. The telomerase complex is comprised of several subunits. In the current study, the authors describe the use of laser capture microdissection (LCM) to procure pure matched tumor and normal cell populations from histologic sections and to determine the expression of telomerase subunits in these purified samples., Methods: Pure matched tumor and normal prostate epithelial cells were procured by LCM using fresh frozen tissue samples obtained from patients undergoing radical prostatectomy. RNA was extracted from LCM captured cells, and the subunits for telomerase were assayed by reverse transcriptase-polymerase chain reaction., Results: In 18 samples that were captured with LCM, only the catalytic subunit of telomerase, or hTERT, was found to be discriminatory between tumor cells (17 of 18 specimens, 94.4%) and nontumor cells (none of 18 specimens). TP1, a protein that has been shown to be associated with telomerase activity, was expressed in 3 of 18 normal cells (16.7%) and 15 of 18 tumor cells (83.3%). The RNA subunit of telomerase, or hTR, was expressed in 10 of 18 normal cells (55.6%) and 18 of 18 tumor cells (100%). There was no apparent correlation between telomerase subunit(s) expression and Gleason sum score., Conclusions: Molecular analyses of LCM cells from prostate carcinoma patient samples demonstrated transcriptional up-regulation of all telomerase subunits in the prostatic epithelium. However, only the catalytic subunit of telomerase, hTERT, was found to be discriminatory between neoplastic versus normal cells (94.4% vs. 0%). This finding suggests that the hTERT subunit may be a useful marker for the detection of prostate carcinoma and/or a potential target for therapy., (Copyright 2001 American Cancer Society.)

Background: Whether patients who are diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score

Background: Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. In the current study data relating to patients diagnosed with testicular carcinoma in 1985, 1986, 1990, 1991, 1995, and 1996 are described., Methods: The data reported in this review were collected from hospital cancer registries from across the U.S. Case information is submitted to the NCDB following guidelines established by the North American Association of Central Registries. Data items include patient demographics, tumor characteristics, initial course of therapy, and follow-up status. Eight calls for data have yielded a total of 6.9 million cases for the years 1985-1996, including 2280 testicular carcinoma cases in 1985-1986, 5677 cases in 1990-1991, and 7452 cases in 1995-1996. These data represent approximately 22.6%, 47.3%, and 51.4%, respectively, of the estimated cases of testicular carcinoma diagnosed in the U.S. in each of these 3 respective time periods. Cases diagnosed and reported to the NCDB between 1985-1991 and that had been staged according to the 4th edition of the American Joint Committee on Cancer (AJCC) manual for the staging of cancer (1567) were used in the analysis of survival outcomes., Results: Four principle findings are reported. First, young men (age < 25 years) are diagnosed with advanced stage nonseminomatous germ cell tumors more frequently than are older men (age >/= 30 years). Second, although surgery and concomitant radiation are the standard therapy for early stage seminomas, surgery alone increasingly is being used. In the treatment of patients with advanced stage seminomas the use of surgery and radiation has declined slightly whereas surgery with concomitant chemotherapy appears to be employed with greater frequency. Third, surgery alone is the treatment of choice for patients with early stage nonseminomatous germ cell tumors and has been employed with increasing frequency over the three time periods studied. The use of surgery and concomitant chemotherapy has remained relatively stable over time in the treatment of patients with advanced stage nonseminomas. And fourth, survival rates decrease with increasing AJCC stage of disease., Conclusions: The NCDB data regarding testicular carcinoma highlight a number of important trends in the presentation and management of testicular tumors. These trends not only evaluate new protocols of treatment but also can be used to direct new strategies toward achieving earlier patient presentation., (Copyright 1999 American Cancer Society.)

Background: The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma., Methods: Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity., Results: The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate., Conclusions: The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens., (Copyright 1999 American Cancer Society.)

Background: A clinical staging system based on the prostate-specific antigen (PSA) and the calculated prostate carcinoma volume (cVCa) construct previously has been proposed. This study was performed to assess whether this proposed clinical staging system was valid in an independent surgical and radiation data set in patients with clinically localized disease., Methods: Cox regression multivariable analyses were used to assess the significance of staging systems (1992 American Joint Commission on Cancer Staging [AJCC] clinical and pathologic stage, versus cVCa-PSA clinical stage) to predict time to posttherapy PSA failure in 441 and 465 patients managed by surgery and radiation, respectively. Significant staging systems identified using Cox regression were tested further using established comparative measures to define the most clinically useful system., Results: Both the 1992 AJCC pathologic stage and the cVCa-PSA clinical stage were significant predictors of time to postoperative PSA failure (P = 0.0001), whereas only the cVCa-PSA clinical stage was a significant predictor of time to postradiation PSA failure (P = 0.0001) using a Cox regression multivariable analysis. Further analyses using a pairwise comparison of the 1992 AJCC pathologic stage and cVCa-PSA clinical stage found the cVCa-PSA staging system provided a more clinically useful prediction of time to postoperative PSA failure. Specifically, the cVCa-PSA staging system was able to identify surgically managed patients with pathologic AJCC T2 disease who did poorly (3-year bNED = 22%) while also selecting patients with clinical AJCC T2b,c disease that was managed by radiation who did well (3-year bNED = 100%)., Conclusions: A clinical staging system based on parameters obtained during the routine evaluation for AJCC clinical T1,2 prostate carcinoma provided a clinically useful stratification of both postoperative and postradiation PSA failure free survival.

Background: Tumor volume in radical prostatectomies can be determined by several different techniques and appears to predict clinical progression. Greatest tumor dimension and area are easily obtained measures that are both correlated with tumor volume. The authors sought to determine whether greatest tumor dimension and/or area were predictors of prostate specific antigen (PSA) failure in men who underwent radical prostatectomy for adenocarcinoma of the prostate., Methods: Fifty-seven men with prostate carcinoma who underwent surgical resection were followed for a median of 27.2 months (range, 1-112 months); 24 (42%) of these men had PSA failure. Preoperative PSA, Gleason grade, pathologic stage, margin status, and greatest tumor dimension and area were determined, and both univariate and multivariate analyses of the outcomes of PSA failure were performed., Results: In the univariate analysis, larger values of greatest tumor dimension and area were strongly associated with increased incidence of PSA failure (P = 0.0001 and 0.0011, respectively). The forward stepwise multivariate analysis indicated that greatest tumor dimension had marginal statistical significance as a risk factor for PSA failure (P = 0.0577; risk ratio, 1.117). However, in this series, men with a greatest tumor dimension of less than 1 cm did not experience failure, whereas all patients with a greatest tumor dimension of more than 2 cm did., Conclusions: Measuring greatest tumor dimension is a simple, inexpensive predictor of PSA failure in men who have undergone radical prostatectomy.

Background: A clinical staging system for localized prostate carcinoma that provides reliable information on which management decisions regarding an individual patient can be based is lacking. This study compared the abilities of all published proposed clinical staging systems to predict time to prostate specific antigen (PSA) failure after radical prostatectomy or external beam radiation therapy for clinically localized prostate carcinoma., Methods: A total of 1441 clinically localized prostate carcinoma patients who were managed with radical prostatectomy at the University of Pennsylvania in Philadelphia (n = 688) or the Brigham and Women's Hospital in Boston (n = 288) or with external beam radiation therapy at the Joint Center for Radiation Therapy in Boston (n = 465) were entered into this study. Patients who received adjuvant or neoadjuvant hormonal or radiation therapy were excluded. Akaike's Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) estimates, which are comparative measures, were calculated for each clinical staging system. Pairwise comparisons of the AIC and SBC estimates for the most predictive clinical staging systems were performed using a formal bootstrap technique with 2000 replications., Results: Both the staging system based on the risk score and the staging system based on the calculated volume of prostate carcinoma and PSA (cVCa-PSA) optimized the prediction of time to posttreatment PSA failure. The cVCa-PSA system, however, provided a more clinically useful stratification of outcome., Conclusions: Improved clinical staging for patients with localized prostate carcinoma may be possible with parameters obtained during routine evaluation. Validation by other investigators is underway.

A prospective analysis was undertaken to evaluate the efficacy of performing routine whole lung tomography in addition to conventional chest radiography in the initial staging and subsequent management of 120 patients with seminomatous and nonseminomatous germ cell tumors. Two hundred fifty whole lung tomographs were performed on these patients. At presentation, only one patient (0.8%) had positive tomography with simultaneously normal posteroanterior and lateral chest films. On follow-up tomographic examinations, three patients had metastases when chest roentgenographs were normal. In only one patient was therapy altered by tomographic findings. The results indicate that routine whole lung tomography is not useful or cost-effective in the initial staging and subsequent management of patients with germ cell tumors.

Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.

In a retrospective study of 223 testis cancer survivors and 120 controls matched sociodemographically, we examined the relative impact of sociodemographic and clinical factors on long-term outcomes in the areas of sexual function, relationships, employment, and mental outlook. For most of the survivors, testis cancer did not lead to unemployment (4.5%), divorce (6.8%), or disabling psychological problems. Multivariate analysis results confirm that cancer survivors report significantly more infertility and sexual performance distress, but not more desire distress, than the control group. Survivors' sexual impairment varied according to treatment received (and therefore histologic factors) and sociodemographic variables. Parental status (not having children) and education (college or less) independently predict infertility distress, whereas education and lower occupational level independently predicted sexual performance distress. Adjusting for socioeconomic status (SES), the men with advanced testis cancer who received chemotherapy and standard retroperitoneal lymph node dissection (RPLND) had significantly more infertility and performance distress than those men who received other treatments. Neither the treatment or SES variables predicted disrupted relationships or a deteriorated mental outlook. However, men with sexual impairment distress were more likely to report strained relationships and a pessimistic mental outlook. These findings have implications for treatment decisions and can be used to identify subgroups of survivors who could benefit from counseling and sexual rehabilitation services.