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Biomedical subjects

G D Grossfeld

Publications and source records attributed to G D Grossfeld.

At least 37 records · Page 2Linked to original sources
PubMed2000

Does the completeness of prostate sampling predict outcome for patients undergoing radical prostatectomy?: data from the CAPSURE database.

OBJECTIVES: To determine whether more complete sampling of the radical prostatectomy (RP) specimen better predicts outcome after surgery. METHODS: We reviewed pathology reports from 1383 patients enrolled in CaPSURE (a longitudinal registry of patients with prostate cancer) who underwent RP. Specimens were considered step-sectioned only if the entire specimen was submitted for analysis and if sections were taken at 0.5-cm intervals or less. Otherwise, specimens were considered non-step-sectioned. Pathologic stage, Gleason score, surgical margin status, and outcome were compared between groups. Prostate-specific antigen (PSA) recurrence was defined as a PSA level of 0.2 ng/mL or greater on two consecutive occasions after RP. Secondary cancer treatment consisted of radiation or androgen deprivation after RP. Adjuvant treatments occurred within 6 months of RP, and nonadjuvant treatments occurred more than 6 months after RP. Kaplan-Meier event rates of PSA recurrence and secondary treatment were calculated for patients in the step-sectioned and non-step-sectioned groups. RESULTS: No significant differences were found between patients in the step-sectioned and non-step-sectioned groups with respect to pathologic tumor stage, prostatectomy Gleason score, or margin status. Patients in whom step-sectioning was performed had a lower serum PSA at diagnosis than patients in the non-step-sectioned group. When examining all patients, no differences were observed in the use of secondary treatments or PSA recurrence based on the method of pathologic analysis. However, patients with negative margins in whom step-sectioning was performed exhibited significantly lower secondary nonadjuvant treatment use and appeared to have a lower risk of PSA recurrence than similar patients in the non-step-sectioned group. CONCLUSIONS: These data suggest that more complete pathologic analysis of the surgical specimen may better predict outcome for some patients undergoing RP. Additional research is warranted to determine whether such differences justify the additional resources necessary to recommend routine step-sectioning.

Adult↗
PubMed2000

Benign prostatic hyperplasia: clinical overview and value of diagnostic imaging.

The term benign prostatic hyperplasia has traditionally been used to describe a constellation of obstructive and irritative voiding symptoms that occur in men as they age. Such symptomatology may be due to a variety of causes, including prostatic enlargement. Thus, the term lower urinary tract symptoms has replaced BPH to describe this symptom complex. The evaluation and treatment of LUTS continues to be a significant part of urology practice in the United States, as well as a significant component of medical resource utilization. Currently, indication for treatment in patients with LUTS is most often based on subjective measurements of symptom severity and bother. Consequently, imaging does not play a major role in the evaluation of such patients. Recent data suggest that the size of the prostate gland may predict which patients with LUTS will develop progressive symptoms and complications. Moreover, both prostate size and the histologic composition of BPH may help to select patients for specific treatment options. Thus, radiologic imaging may eventually play a larger role in the diagnosis and treatment of LUTS in the future. After review of the literature, it appears that routine upper urinary tract imaging in patients with LUTS or BPH is not warranted. Selective use of such imaging tests in patients with BPH and either hematuria, laboratory evidence of renal insufficiency (elevated BUN or creatinine), or a history of urinary tract infection, urolithiasis, previous urinary tract surgery, or congenital or acquired renal disease remains indicated. Local imaging of the prostate can be performed with either MR imaging or TRUS. Although MR imaging provides excellent resolution of internal prostatic anatomy, information with respect to the ratio of glandular to stromal tissue in the prostate, and an accurate estimate of prostate volume, its use in patients with BPH is limited by its high cost and limited availability. In contrast, TRUS remains an important tool in the evaluation of patients with prostatic disease. Similar to MR imaging, TRUS provides excellent images of internal prostatic anatomy and an accurate estimate of prostate volume prior to treatment. In addition, this imaging modality is noninvasive, cost-efficient, easily adapted to office use, and able to provide guidance for transrectal prostate biopsy.

Biopsy↗
PubMed2000

The prostatic gland: malignancies other than adenocarcinomas.

Many rare variants of prostatic carcinoma have been described and characterized in recent years. Accurate diagnosis of these variants is necessary in order to determine appropriate therapy. Unusual tumors arising in the prostate raise questions of histogenesis, and may carry a better or worse prognosis than typical adenocarcinoma. Virtually the entire spectrum of cellular differentiation has been observed within prostatic epithelium, and rare neoplasms exhibit these unusual forms of differentiation as the chief component of the tumor. Except in sarcoma (marked prostatic enlargement), imaging plays a limited role in the diagnoses of these entities. Biopsy and histologic diagnoses are essential and the role of imaging is restricted to the evaluation of locoregional and distant spread of the disease.

Adenocarcinoma↗
PubMed2000

Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database.

PURPOSE: We determined the impact of positive surgical margins on prostate specific antigen (PSA) recurrence and secondary treatment in patients who underwent radical prostatectomy as definitive local treatment for prostate cancer. MATERIALS AND METHODS: We reviewed the pathology reports of 1,383 patients in the CaPSURE database, a longitudinal disease registry of men with prostate cancer, who underwent radical prostatectomy as definitive local treatment. Pathological stage, Gleason score, and the number and location of any positive surgical margins were determined in each patient. PSA recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy. Secondary cancer treatment consisted of radiation or androgen deprivation after radical prostatectomy. Adjuvant and nonadjuvant secondary treatment was given within and more than 6 months after radical prostatectomy, respectively. Kaplan-Meier event rates of PSA recurrence and secondary treatment were calculated for patients with positive and negative surgical margins. We performed multivariate Cox proportional hazards analysis to adjust for clinical differences in groups. RESULTS: Patients with positive surgical margins were significantly more likely to undergo secondary adjuvant or nonadjuvant cancer treatment and have PSA recurrence than those with negative margins. After adjusting for patient age, ethnicity, PSA at diagnosis, pathological stage and Gleason score, surgical margin status was an important independent predictor of PSA recurrence and secondary treatment (p = 0.06 and 0.0011, respectively). The number of positive margins and positive margin location had little impact on the outcomes measured. CONCLUSIONS: These data indicate that surgical margin status is an independent predictor of PSA recurrence and secondary cancer treatment in patients who underwent radical prostatectomy as definitive local therapy for prostate cancer.

Adult↗
PubMed2000

Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from The CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor.

PURPOSE: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients. MATERIALS AND METHODS: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation. RESULTS: Compared with others in the database, patients on watchful waiting were more likely to be 75 years old or older (51% versus 16%, p <0.001), white (93% versus 85%, p <0.001), and have lower serum PSA (p <0.001), organ confined disease (97% versus 88%, p <0.001) and a total Gleason score of 7 or less (97% versus 88%, p <0.001). In the watchful waiting group there was a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis. Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant predictor of treatment. CONCLUSIONS: Men who elect initial watchful waiting for prostate cancer tend to be older, have lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA at diagnosis is the dominant factor for predicting secondary treatment.

Aged↗
PubMed2000

Management of a positive surgical margin after radical prostatectomy: decision analysis.

PURPOSE: We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy. MATERIALS AND METHODS: We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome. RESULTS: Using average probability estimates from a literature review the decision model recommended initial surveillance. Sensitivity analysis demonstrated that the model depended on the probability of disease recurrence in men followed expectantly after surgery as well as the efficacy of therapeutic radiation. We tested the decision model again for patient groups based on tumor grade, pathological stage, preoperative PSA and number of positive margins. The model recommended initial radiation for patients with low to intermediate grade disease, no evidence of seminal vesicle invasion and multiple positive margins. CONCLUSIONS: The results of our decision analysis imply that immediate radiation may be appropriate for patients with a positive surgical margin(s) and a high likelihood of recurrent local rather than distant disease. This model may be useful to physicians and patients who use individual probability estimates and utility values to determine the preferred course of management after surgery.

Decision Trees↗
PubMed1999

Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell.

Animals↗
PubMed1999

Radiotherapy after radical prostatectomy: treatment outcomes and failure patterns.

OBJECTIVES: To define the optimal role for radiotherapy (RT) after radical prostatectomy (RP) and to characterize specific patterns of PSA failure in this setting. METHODS: The records of 105 patients who underwent RT after RP (69 received therapeutic RT because of an elevated prostate-specific antigen [PSA] level, 36 received immediate adjuvant RT) were reviewed. The median follow-up was 35 months after RT and 57 months after RP. Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative, pathologic, and postoperative characteristics were examined for their ability to predict success after RT. Patterns of PSA recurrence after RT were also examined by determining the PSA nadir, PSA velocity, and timing of androgen-deprivation therapy. RESULTS: Of 105 patients, 47 experienced biochemical failure. Actuarial 3 and 5-year progression-free survival estimates for all patients were 55% and 43%, respectively. Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT. However, patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT. Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT. Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity (1.5 ng/mL/yr). Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity (0.36 ng/ml/yr). CONCLUSIONS: RT is effective in select patients after RP. Given the low PSA velocity consistent with persistent local disease in nearly 50% of patients in whom RT failed, more effective local therapy is needed after RP in high-risk patients.

Aged↗
PubMed1999

The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience.

PURPOSE: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months. RESULTS: Serial PSA data was available after 181 initial and repeat procedures. Nadir PSA was undetectable in 88 patients (49%), between 0.1 and 0.4 ng./ml. in 39 (21%) and 0.5 ng./ml. or greater in 54 (30%) following cryosurgery. After 78 of these procedures (43%) serum PSA reached a nadir of less than 0.5 ng./ml. and failed to increase greater than 0.2 ng./ml. on at least 2 occasions. Prostate biopsy was performed following 167 procedures and was positive after 64 (38%). CONCLUSIONS: Cryosurgery was associated with favorable serum PSA characteristics in 49% of patients 3 years after treatment. Undetectable PSA nadir and pretreatment PSA 10 ng./ml. or less were associated with a favorable outcome, with a biochemical disease-free survival of 77% and 61% 3 years after treatment, respectively.

Actuarial Analysis↗
PubMed1998

Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer.

BACKGROUND: Altered expression of p53 protein is an important predictor of progression in bladder cancer. The action of p53 on cell cycle regulation is mediated, in part, through expression of the cyclin-dependent kinase inhibitor p21WAF/CIP1 (p21). Loss of p21 expression may, therefore, contribute to tumor progression. We sought to determine the relationship between p21 expression in bladder cancer and disease progression. METHODS: Tumor specimens were obtained from 242 patients who underwent cystectomy for bladder cancer. Median follow-up was 8.5 years (range, 0.1-11.8 years). Nuclear p21 status was determined by immunohistochemistry and was then analyzed in relationship to the probability of tumor recurrence, overall survival, and tumor p53 status. Reported P values are two-sided. RESULTS: Nuclear p21 expression was detected in the tumors of 156 (64%) of the 242 patients. Patients with p21-positive tumors had a decreased probability of tumor recurrence (P<.00001) and an increased probability of overall survival (P<.00001) in comparison with patients with p21-negative tumors. In a multivariable analysis, p21 expression was an independent predictor of tumor recurrence (P = .0017) and of survival (P = .006) when assessed with tumor grade, tumor stage, lymph node status, and p53 status. p21 expression was associated with p53 status (P<.001); 56% of tumors with p53 alterations showed loss of p21 expression, whereas 79% of tumors expressing wild-type p53 were p21 positive. Patients with p53-altered/p21-negative tumors demonstrated a higher rate of recurrence and worse survival compared with those with p53-altered/p21-positive tumors (P<.0001). Patients with 53-altered/p21-positive tumors demonstrated a similar rate of recurrence and survival as those with p53-wild type tumors. CONCLUSION: Loss of p21 expression is a statistically significant and independent predictor of bladder cancer progression. Maintenance of p21 expression appears to abrogate the deleterious effects of p53 alterations on bladder cancer progression.

Aged↗
PubMed1998

Prognostic markers in bladder cancer: a contemporary review of the literature.

PURPOSE: We provide a contemporary review of bladder tumor markers and summarize their role as prognostic indicators. MATERIALS AND METHODS: A comprehensive review of the literature on prognostic markers for transitional cell carcinoma of the bladder was performed. RESULTS: Intense research efforts are being made to identify and characterize better various bladder cancers and their true biological potential. The need to predict which superficial tumors will recur or progress and which invasive tumors will metastasize has led to the identification of a variety of potential prognostic markers. Blood group antigens, tumor associated antigens, proliferating antigens, oncogenes, peptide growth factors and their receptors, cell adhesion molecules, tumor angiogenesis and angiogenesis inhibitors, and cell cycle regulatory proteins have recently been identified. The potential clinical applications of these tumor markers are under active investigation. Recent attention has focused on which tumor markers may predict the responsiveness of a particular bladder cancer to systemic chemotherapy. CONCLUSIONS: At present conventional histopathological evaluation of bladder cancer (tumor grade and stage) cannot predict accurately the behavior of most bladder tumors. With a better understanding of the cell cycle, and cell to cell and cell to extracellular matrix interactions as well as improved diagnostic techniques (immunohistochemistry), progress is being made to identify and characterize other potential prognostic markers for transitional cell carcinoma of the bladder. The ultimate goal is to develop reliable prognostic markers that will accurately predict not only the course but also the response of a tumor to therapy. This information may then be used to dictate more aggressive treatment for tumors that are likely to progress and less aggressive treatment for those that are unlikely to progress. In the future these biological markers may also be used in gene therapy for the treatment of bladder cancer.

Antigens, Neoplasm↗
PubMed1998

Intermittent androgen deprivation for clinically localized prostate cancer: initial experience.

OBJECTIVES: To evaluate the use of intermittent androgen deprivation (IAD) in the treatment of selected patients with clinically localized prostate cancer. METHODS: We report our initial experience with 47 patients (aged 50 to 92 years) treated with IAD for clinically localized prostate cancer (Stage T1c in 3 patients, T2 in 21, T3 in 21, T4 in 1, and unknown in 1). No patient was found to have systemic disease prior to the initiation of therapy. Twenty-seven patients with localized cancers refused local therapy and have been treated with IAD only. Seven patients developed recurrent disease following radiotherapy, 2 following cryotherapy, 8 following radical prostatectomy, and 3 following radical prostatectomy with adjuvant radiotherapy. Mean and median serum prostate-specific antigen (PSA) prior to the start of treatment were 20.5 and 8.4 ng/mL, respectively (range 0.6 to 190). Androgen deprivation was continued 1 to 2 months after serum PSA became undetectable or a nadir level was reached. Therapy was then reinstituted after serum PSA reached a predetermined level. Thirty-three patients have been treated with total androgen blockade and 14 have been treated with a luteinizing hormone-releasing hormone agonist only. RESULTS: Follow-up ranges from 5 to 52 months from the start of treatment (mean 24 months). Patients have received from 1 to 5 treatment cycles (median 2 cycles), with the mean and median cycle lengths being 15 and 14 months, respectively. Eighteen patients are currently on cycle 1, 15 on cycle 2, 11 on cycle 3, 1 on cycle 5, and 1 patient has discontinued treatment after undergoing salvage radical prostatectomy. The mean and median nadir serum PSA on androgen deprivation have been 0.2 and 0.0 ng/mL, respectively. Nadir PSA was reached within an average of 4 months (range 1 to 11) after initiating treatment. The mean serum PSA at the start of cycle 2 was 7.0 ng/mL (range 0.6 to 19.1). Only 1 patient has failed to respond to reinstitution of treatment; this patient was found to have metastatic disease during his second cycle of treatment (time to progression 25 months from the start of IAD). No other patient has demonstrated disease progression during the follow-up period. Patients have spent an average of 47% of the time off of therapy. CONCLUSIONS: IAD appears to be a viable treatment option in selected patients with clinically localized prostate cancer. However, the durability and advantage of IAD, if any, over continuous therapy is unknown at present. Consequently, at the present time IAD should be considered an investigative form of treatment for patients with prostate cancer.

Adenocarcinoma↗
PubMed1998

Prospective pathologic analysis of female cystectomy specimens: risk factors for orthotopic diversion in women.

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.

Adult↗
PubMed1998

Long-term side effects of treatment for testis cancer.

Patients newly diagnosed with testis cancer can now expect excellent results with respect to long-term, disease-free survival after treatment. Given the young age of presentation for many of these patients, the long-term consequences of curing testis cancer have become a major concern. Surgery, radiation, and chemotherapy for testis cancer have all been associated with potential long-term side-effects. Consequently, new treatment regimens have been directed toward minimizing these possible side-effects while at the same time maintaining high cure rates (i.e., limiting the size of radiation fields, decreasing the number of chemotherapy cycles, eliminating bleomycin). Patients and physicians must be made aware of the potential adverse side effects of treatment for testis cancer. At the present time, however, it appears that the beneficial effects of such treatment, with respect to overall and disease-free survival, far outweigh the limited probability of persistent treatment-related side effects in patients newly diagnosed with testis cancer.

Antineoplastic Agents↗
PubMed1998

Evaluation of asymptomatic microscopic hematuria.

Asymptomatic microscopic hematuria continues to be a common cause for urologic referral. Depending on the population under investigation, the condition is reported in 0.2% to 21.1% of subjects. Many possible etiologies exist for the presence of asymptomatic microscopic hematuria, ranging from insignificant lesions to potentially life-threatening lesions that may require urgent treatment. A cause for asymptomatic microscopic hematuria can be determined in 32% to 100% of patients undergoing a full urologic evaluation, with 3.4% to 56% of these patients having either moderately or highly significant lesions at the time of diagnosis. Consequently, full urologic evaluation is warranted in the majority of patients referred to a urologist with asymptomatic microscopic hematuria. In patients in whom no diagnosis is reached after initial evaluation, follow-up is necessary, although the extent and timing of such follow-up have not been adequately investigated. The ultimate goal of evaluating any patient with asymptomatic microscopic hematuria is the discovery of a significant lesion at an early stage when it is amenable to curative therapy and prior to that lesion causing significant morbidity. No randomized, prospective studies have compared the outcomes of patients with asymptomatic microscopic hematuria undergoing full evaluation with those of patients undergoing surveillance only. The data obtained in high-risk groups undergoing urinary dipstick screening for bladder cancer suggest that the bladder tumors discovered when evaluating all patients with asymptomatic microscopic hematuria may be more amenable to treatment than those normally encountered, thereby possibly reducing the mortality and morbidity associated with bladder cancer in these patients. These findings support the evaluation of patients with asymptomatic microscopic hematuria in a cost-conscious medical environment.

Algorithms↗