Biomedical subjects

Martha K Terris

Publications and source records attributed to Martha K Terris.

At least 19 recordsLinked to original sources

PubMed2026

Oncogenic PIK3CA reprograms glutamine metabolism to drive bladder cancer progression.

BACKGROUND: Genomic analysis has revealed that approximately 40% of bladder cancer (BLCA) tumors harbor alterations in the PI3K/AKT pathway, with PIK3CA mutations occurring in 15-25% of cases. PIK3CA, which encodes the catalytic p110α subunit of PI3K, plays a critical role in regulating cell survival, proliferation, and metabolism. However, the metabolic and functional consequences of PIK3CA mutations in BLCA remain poorly defined. METHODS: To investigate the role of PIK3CA mutations in BLCA, we performed targeted sequencing on tumors from patients, identifying recurrent alterations. Using CRISPR/Cas9 knock-in models in SCaBER and UM-UC-3 cell lines, we introduced the PIK3CA E545K mutation to study its effects. We conducted transcriptomic profiling, targeted metabolomics, and stable isotope tracing to assess metabolic reprogramming. Functional assays measured proliferation, mitochondrial complex I activity, and glutaminolysis. Orthotopic xenografts in mice were used to evaluate in vivo tumor growth and metabolism. RESULTS: PIK3CA mutations were present in 20% of cases, consistent with TCGA data. The E545K and E545Q hotspots accounted for 70% of these mutations. PIK3CA E545K strongly activated PI3K/AKT signaling. Transcriptomic analysis revealed enrichment of OXPHOS, fatty acid metabolism, and mTORC1 signaling. Metabolomics indicated changes in TCA cycle metabolites and enhanced reductive carboxylation of glutamine to citrate, driving fatty acid synthesis. Mutant cells showed increased expression of GLS1 and FASN, higher proliferation rates, and elevated mitochondrial complex I activity. In vivo, PIK3CA-mutant xenografts displayed significantly increased tumor growth. CONCLUSION: PIK3CA mutations are frequent drivers of metabolic reprogramming in BLCA, leading to increased glutamine flux, elevated OXPHOS activity, and enhanced fatty acid synthesis, all of which contribute to tumor progression. These findings provide the first comprehensive evidence that PIK3CA-driven metabolic alterations are both biomarkers of aggressive disease and actionable therapeutic targets. The efficacy of PI3Kα inhibition in combination with metabolic targets may support its potential in precision medicine for PIK3CA-mutant BLCA and highlights the value of integrating metabolic biomarkers into treatment strategies for advanced BLCA.

Journal Article↗

PubMed2007

Changing nature of high risk patients undergoing radical prostatectomy.

PURPOSE: We examined the outcomes of radical prostatectomy alone in high risk patients with prostate cancer and evaluated changes in high risk prostate cancer outcomes with time. MATERIALS AND METHODS: From 1988 to 2003, 251 men with high risk prostate cancer (prostate specific antigen more than 20 ng/ml and/or biopsy Gleason greater than 7) were identified in a cohort of 1,796 (14%) enrolled in the Shared Equal Access Regional Cancer Hospital Database. Temporal changes in clinicopathological characteristics and prostate specific antigen recurrence rates were examined stratified by 4, 4-year periods. RESULTS: With time significantly more men were considered at high risk due to a high biopsy Gleason score relative to prior years, when the most common reason for being considered at high risk was increased PSA (p <0.001). Only 3% of high risk men from 2000 to 2003 had increased prostate specific antigen and high biopsy Gleason score compared to 23% from 1988 to 1991. With time there were no differences in biochemical recurrence rates (p = 0.147). Men with a high biopsy Gleason score and increased prostate specific antigen had worse outcomes than men with only a high Gleason score or men with only high prostate specific antigen (p = 0.046 and 0.081, respectively). On multivariate analysis that only included preoperative clinical characteristics only prostate specific antigen was an independent predictor of prostate specific antigen failure following radical prostatectomy (p = 0.014). There was a trend, which did not attain statistical significance, for higher biopsy Gleason scores and higher clinical stage to be associated with higher failure rates (p = 0.060 and 0.081, respectively). CONCLUSIONS: Patients are designated as high risk by Gleason grade more commonly now than early in the prostate specific antigen era. Outcomes in high risk patients undergoing radical prostatectomy alone have not significantly improved with time. New treatment strategies, such as multimodality therapy, are needed to improve outcomes in high risk patients with prostate cancer.

Aged↗

PubMed2006

Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy.

BACKGROUND: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the risk of biochemical recurrence after radical prostatectomy. The performance of the index is at least as good as the best available instruments based on clinical variables, and the 0 to 10 score is simple to calculate for both clinical and research purposes. This study used a large external dataset to validate CAPRA. METHODS: Data were abstracted from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the database, 1346 (64%) had full data available to calculate the CAPRA score. Performance of the CAPRA score was assessed with proportional hazards regression, survival analysis, and the concordance (c) index. RESULTS: Of the studied patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six percent suffered recurrence; median follow-up among patients who did not recur was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39 (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients. Increasing CAPRA scores were significantly associated with increasing risk of adverse pathologic outcomes. The c-index for CAPRA for the validation set was 0.68, compared with 0.66 for the original development set. CONCLUSIONS: The UCSF-CAPRA accurately predicted both biochemical and pathologic outcomes after radical prostatectomy among a large, diverse, cohort of men. These results validated the effectiveness of this powerful and straightforward instrument.

Adult↗

PubMed2006

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.

Aged↗

PubMed2006

Is biopsy Gleason score independently associated with biochemical progression following radical prostatectomy after adjusting for pathological Gleason score?

PURPOSE: Biopsy Gleason score is known to be associated with prostate specific antigen failure following radical prostatectomy. However, it is unclear whether it remains associated with outcome after surgery when the pathological Gleason score is known. MATERIALS AND METHODS: We determined the association between biopsy Gleason score and biochemical progression after correcting for preoperative and postoperative characteristics, including pathological Gleason score, in 1,931 men treated with radical prostatectomy between 1988 and 2005 in the Shared Equal Access Regional Cancer Hospital Database Study Group database. Gleason score was examined as a categorical variable of 2 to 6, 3 + 4 and 4 + 3 or greater. RESULTS: Higher biopsy Gleason scores were positively associated with extracapsular extension (p <0.001), positive surgical margins (p <0.001), seminal vesicle invasion (p <0.001), positive lymph nodes (p <0.001) and biochemical progression (log rank p <0.001). After adjusting for only preoperative characteristics biopsy Gleason 3 + 4 and 4 + 3 or greater were associated with increased risk of biochemical progression compared to biopsy Gleason 6 or less (p = 0.001 and <0.001, respectively). After further adjusting for multiple pathological characteristics, including pathological Gleason score, the association between higher biopsy Gleason score and progression was little changed, in that men with biopsy Gleason 3 + 4 and 4 + 3 or greater were significantly more likely to experience progression (p = 0.001 and <0.001, respectively). Furthermore, when stratified by pathological Gleason score, higher biopsy Gleason scores were associated with an increased risk of biochemical progression in each pathological Gleason score category (log rank p </=0.007). CONCLUSIONS: Biopsy Gleason score remained strongly associated with progression even when the pathological Gleason score was known and controlled for. If confirmed at other centers, incorporation of biopsy Gleason score into postoperative nomograms designed to estimate the progression risk might improve model precision.

Aged↗

PubMed2006

Association between marijuana use and transitional cell carcinoma.

OBJECTIVES: Marijuana smoking has been implicated as a causative factor in traditionally tobacco-related tumors of the head and neck and of the lung. When associated with marijuana use, such tumors occur in a much younger patient population than do similar tumors in tobacco smokers. Owing to the large number of young men with a history of marijuana presenting with transitional cell carcinoma to VA facilities, this study was designed to compare the marijuana use among young (aged less than 60 years) transitional cell carcinoma patients with that among age-matched controls. METHODS: Fifty-two men aged less than 60 years presenting consecutively with transitional cell carcinoma and 104 age-matched controls (defined by having no history of transitional cell carcinoma, hematuria, or irritative voiding symptoms, as well as unremarkable results on urinalysis and urine cytology) completed questionnaires about exposure to various potential carcinogens, including radiation, Agent Orange, smoked or processed meats, dyes, tobacco, and marijuana. RESULTS: Of the 52 transitional cell carcinoma patients, 46 (88.5%) reported a history of habitual marijuana usage, and 72 (69.2%) of the age-matched controls gave a history of habitual marijuana use. This difference was statistically significant (P = 0.008). In those with transitional cell carcinoma, marijuana use significantly correlated with tumor stage, grade, and number of recurrences. CONCLUSIONS: Marijuana smoking might increase the risk of transitional cell carcinoma.

Carcinoma, Transitional Cell↗

PubMed2006

Assessment of patient concern and adequacy of informed consent regarding infertility resulting from prostate cancer treatment.

OBJECTIVES: To address in a questionnaire-based study the frequency at which fertility is a concern for men when they consider their prostate cancer treatment options. A secondary aim was to assess the rate at which men were informed of the fertility implications of prostate cancer treatment by their physician before their selection of a treatment option. METHODS: Two questionnaires were used. One questionnaire was distributed to men with localized prostate cancer who had undergone treatment within the past year. These questions addressed whether continence, erectile function, and fertility were discussed with them by their physician during the prostate cancer treatment selection process. The second questionnaire was distributed to men with newly diagnosed prostate cancer and queried their level of concern about the effects of prostate cancer treatment on sexual function, urinary function, and fertility. RESULTS: All patients receiving the first questionnaire stated that they were informed of the incontinence and impotence side effects of prostate cancer treatments, but only 8.7% stated that they were informed of the effect that prostate cancer treatments would have on their future fertility. Of the patients completing the second questionnaire, 53.7% responded that incontinence was the side effect of prostate cancer treatment that caused them the most concern, 42.6% stated that erectile dysfunction was the most concerning, and 3.7% listed fertility as the major concern. CONCLUSIONS: Urologists should consider approaching the topic of infertility when discussing the pros and cons of various prostate cancer therapies with their younger patients.

Adult↗

PubMed2006

Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection.

PURPOSE: Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. MATERIALS AND METHODS: We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. RESULTS: On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). CONCLUSIONS: In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology.

Humans↗

PubMed2006

Delay of radical prostatectomy and risk of biochemical progression in men with low risk prostate cancer.

PURPOSE: Men newly diagnosed with prostate cancer are faced with multiple treatment options. Understanding these options and their associated side effects, and making a decision often requires time, resulting in a delay before receiving treatment. This is particularly pertinent in men with low risk disease who may be considered candidates for watchful waiting and, thus, may not experience strong pressure to undergo treatment promptly. Whether delays and especially prolonged delays, eg greater than 180 days, before RP negatively impact the disease outcome is unclear. MATERIALS AND METHODS: We examined the association between time from diagnosis to surgery, and pathological features of the RP specimen and risk of biochemical progression in 895 men with low risk prostate cancer (prostate specific antigen less than 10 ng/ml and biopsy Gleason sum 6 or less) treated with RP between 1988 and 2004 in the Shared-Equal Access Regional Cancer Hospital Database using logistic regression and Cox proportional hazards, respectively. RESULTS: Time from biopsy to surgery was not significantly related to high grade disease in the RP specimen, positive surgical margins or extraprostatic extension (all p-trend >0.05). After adjustment for multiple clinical covariates a longer time from biopsy to surgery was significantly associated with an increased risk of biochemical progression (p-trend = 0.002). However, this increased risk of progression was only apparent in men with delays greater than 180 days (median 263, vs 90 or fewer days RR 2.73, 95% CI 1.51 to 4.94). CONCLUSIONS: Our data suggest that patients with low risk prostate cancer can be reassured that immediate treatment is not necessary. Whether long delays (greater than 180 days) decrease the likelihood of curability in some patients requires further study.

Disease Progression↗

PubMed2006

Evaluation of fluorodeoxyglucose positron emission tomography imaging in metastatic transitional cell carcinoma with and without prior chemotherapy.

INTRODUCTION: This study was designed to determine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of metastatic transitional cell carcinoma (TCC). METHODS: Fifty-eight FDG PET scans were performed on 46 consecutive patients with TCC. Results were correlated with radiologic, pathologic, and histologic findings in these patients and the sensitivity of PET for detecting malignancy in untreated TCC patients (n = 48) was compared to the sensitivity in patients who had undergone prior chemotherapy (n = 10). RESULTS: Of 48 scans in patients who had no prior systemic chemotherapy, 10 had increased uptake in proven metastatic TCC lesions and 3 PET studies failed to reveal metastatic TCC (sensitivity 76.9%). In patients free of metastatic disease, 33 revealed no abnormal uptake and 1 study revealed a suspicious area in a patient free of metastases (specificity = 97.1%). However, in 10 patients imaged after receiving chemotherapy, the sensitivity fell to 50% for the detection of histologically confirmed residual/recurrent tumor by PET. CONCLUSIONS: FDG PET detects increased metabolic activity. After chemotherapy, viable cancer cells may still be present but with a diminished metabolic rate. As a result, PET imaging is often useful in the evaluation of untreated metastatic TCC metastasis but should be interpreted with caution in patients who have received prior chemotherapy.

Aged↗

PubMed2005

Racial differences in prognostic value of adult height for biochemical progression following radical prostatectomy.

PURPOSE: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. EXPERIMENTAL DESIGN: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. RESULTS: Taller men (>175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stage T(1) disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (< or =175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (P(interaction) = 0.05). CONCLUSIONS: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor-binding protein-3 concentrations among Black men may be involved.

Aged↗

PubMed2005

Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study.

PURPOSE: Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. RESULTS: In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06). CONCLUSION: Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.

Humans↗

PubMed2005

Body mass index as a predictor of prostate cancer: development versus detection on biopsy.

OBJECTIVES: To determine whether obesity is biologically associated with an increased risk of prostate cancer development, especially aggressive disease and to explore whether a bias may exist in our ability to detect these cancers in obese patients. METHODS: We evaluated the association of body mass index (BMI) with prostate cancer, biopsy Gleason sum, and amount of cancer using logistic and linear regression analyses adjusting for age at biopsy, race, prostate-specific antigen level, digital rectal examination findings, and prostate volume among 787 consecutive men undergoing prostate biopsy between 1998 and 2002 at an equal-access medical center. RESULTS: Men with a higher BMI were younger (P < 0.001), had lower prostate-specific antigen concentrations (P = 0.02), fewer abnormal digital rectal examination findings (P = 0.02), and larger prostate volumes (P < 0.001). After adjusting for age, no overall association was found between BMI and the odds of being diagnosed with cancer (P trend = 0.89), although overweight and mild obesity were inversely associated with the diagnosis of cancer. After multivariable adjustment, a higher BMI was associated with an increased odds of being diagnosed with prostate cancer (P trend = 0.007). Among men diagnosed with cancer, and after multivariable adjustment, a higher BMI was associated with a similar percentage of biopsy tissue with cancer (P trend = 0.23), but with greater odds of a high Gleason sum (P trend = 0.004). CONCLUSIONS: After taking into account the clinical characteristics that influence the likelihood of finding an existent cancer, a higher BMI was positively associated with being diagnosed with prostate cancer. Also, among the men with cancer, a higher BMI increased the odds of high-grade disease. These findings suggest that obesity may be biologically associated with prostate cancer development and, in particular, with high-grade disease.

Aged↗

PubMed2005

Interval from prostate biopsy to radical prostatectomy: effect on PSA, Gleason sum, and risk of recurrence.

OBJECTIVES: To determine whether the change in prostate-specific antigen (PSA), change in Gleason sum, and/or interval between prostate biopsy and radical prostatectomy have an association with biochemical recurrence. METHODS: The relationship between biochemical recurrence and the interval between biopsy and surgery, as well as the rate and amount of change in PSA and Gleason sum from biopsy to surgery, was evaluated in 151 patients with prostate cancer treated with radical prostatectomy. RESULTS: A statistically significant increase was found in PSA level and Gleason sum between biopsy and surgery (P = 0.01 and P < 0.0001, respectively). No significant association was found between prebiopsy PSA level (P = 0.27) or biopsy Gleason sum (P = 0.07) with biochemical recurrence as independent variables or in a combined model (P = 0.12). An association was also not found between recurrence and preprostatectomy PSA level (P = 0.15) or the rate of PSA change (P = 0.28) as independent variables. However, a significant association was found with the prostatectomy Gleason sum (P = 0.001). In a combined model, a significant association was noted between the preprostatectomy PSA level and prostatectomy specimen Gleason sum and biochemical recurrence (P = 0.003). No increased risk of biochemical recurrence was noted with increasing time from biopsy to prostatectomy (odds ratio 1.00) or the rate (odds ratio 1.03) and degree (odds ratio 1.30) of serum PSA or Gleason sum (odds ratio 1.07). CONCLUSIONS: The interval between biopsy and radical prostatectomy is not a predictor of biochemical failure. An association was noted between an increased risk of biochemical failure and the amount of serum PSA and Gleason sum increase between biopsy and surgery.

Adult↗

PubMed2005

Prostate biopsy volume indices do not predict for significant Gleason upgrading.

Significant discordance exists between biopsy and matched prostatectomy grades. This study tests the hypothesis that surrogate tumor volume indices available from biopsies could yield an improved prediction of the underlying pathologic Gleason grade. Records of 124 patients who underwent radical prostatectomy were reviewed. Biopsies were characterized by primary and secondary Gleason grade, number of positive cores, and linear tumor length. Surgical specimens were characterized by primary and secondary Gleason grade, organ-confined disease, seminal vesicle invasion, and margins. Biochemical failure (BF) was defined by a postoperative prostate-specific antigen >0.05 ng/mL. There were 28 patients (24%) who experienced biochemical failure. On multivariate analysis, only the pathologic Gleason sum (P = 0.012) and the cumulative tumor length (P = 0.050) were independently associated with BF, and only the cumulative tumor length was associated with nonorgan-confined disease (P = 0.034). For patients with a cumulative tumor length >10 mm, 49% (18 of 37) had nonorgan-confined disease and 37% (13 of 35) had BF compared with 29% (25 of 87) and 19% (15 of 80), respectively, if they had cumulative tumor length < or =10 mm (P <0.034). Overall, an exact match was seen in 39% of biopsy Gleason grades, whereas 21% were downgraded by 1 or more points, and 41% were upgraded by 1 or more points. On univariate or multivariate analysis, none of the biopsy surrogate volume indices examined achieved significance or suggested a trend in predicting for a clinically meaningful grade change. Although indices of tumor volume from prostate needle biopsies independently predict for organ-confined disease and BF after prostatectomy, none predicted for a clinically significant upgrading or downgrading of biopsies. This suggests that the correlation that exists between such volume surrogates and outcomes after surgery reflect tumor volume effects only, independently of any possible association between tumor volume and Gleason grade.

Adenocarcinoma↗

PubMed2005

Status of women in urology: based on a report to the Society of University Urologists.

PURPOSE: Written responses from American trained women in urological surgery were obtained to evaluate practice patterns, career choices and workplace satisfaction. MATERIALS AND METHODS: A 3-page unblinded questionnaire was mailed in March 2003 to American trained women in urological surgery available through the databases of the Society of Women in Urology with subsequent statistical analysis. RESULTS: The response rate was 60% but inclusive of all women in current academic practice in the United States. A total of 61% reported working 51 or more hours a week whereas 2% have left practice due to retirement or medical infirmity. There were 41% who had completed fellowships including 87% reporting active practice within their subspecialty, whereas 62% of fellowship trained surgeons remained in an academic practice. Among United States women in academic urological practice, academic progression has occurred in a third of this cohort. CONCLUSIONS: Threats to successful practice, consistent with other workplace surveys of physicians and professional women including gender based role limitation and inadequate mentoring, were commonly reported. These correctable workplace deficiencies represent an opportunity for American urology to enhance the professional workplace for all urologists regardless of gender.

Female↗

PubMed2005

Primary care providers' attitudes toward prostate cancer risk factors at a Veterans Affairs health care facility.

OBJECTIVE: We asked what factors influence primary care providers' decision to screen patients for prostate cancer. METHODS: A survey completed by 175 Veterans Affairs primary care providers queried whether patient anxiety, family history, race, and other assorted risk factors increased their likelihood of screening for prostate cancer. Subsequent questions assessed the degree to which various factors, such as age, comorbidities, and lack of interest, decreased their likelihood of screening. RESULTS: The African American race increased the tendency for screening for 84.6%, followed by a family history of prostate cancer for 73.3%. Life expectancy of less than 5 years substantially decreased the tendency to screen for only 42.3%. Only 28% thought that age of more than 75 years was a deterrent to screening. CONCLUSIONS: Veterans Affairs primary care providers recognize the need to aggressively screen African Americans and men with a family history of prostate cancer. However, they often screen men with a limited life expectancy or advanced age.

Adult↗

PubMed2004

Biochemical outcome after radical prostatectomy among men with normal preoperative serum prostate-specific antigen levels.

BACKGROUND: Recent studies have shown that a significant number of men with normal prostate-specific antigen (PSA) levels have prostate carcinoma. Whether malignancies in such men are associated with better outcomes is unclear. The authors compared the risk of biochemical failure after radical prostatectomy (RP) between men with normal PSA levels and men with elevated PSA levels. METHODS: Data were examined from 1582 men who underwent RP between 1988 and 2002 at 1 of 5 equal-access medical centers. Patients were segregated into groups based on serum PSA levels (with stratification according to age-specific reference ranges). Clinical and pathologic characteristics and biochemical outcome data were compared across groups using analyses of variance, log-rank tests, and Cox proportional hazards analysis. RESULTS: Men who had normal PSA levels had significantly fewer high-grade tumors compared with men who had higher PSA levels (P < 0.001). The former group had a significantly decreased incidence of positive surgical margins, extracapsular disease, seminal vesicle invasion, and lymph node involvement (P < 0.001). On multivariate analysis, only serum PSA level (P < 0.001) and biopsy Gleason score (P < 0.001) predicted the time to disease recurrence. When only men with serum PSA levels < 10 ng/mL were examined, PSA level treated as a continuous variable remained a significant predictor of time to biochemical failure (P = 0.02). CONCLUSIONS: Men who had normal PSA levels had significantly fewer high-grade tumors and significantly better biochemical outcomes after undergoing RP compared with men who had elevated PSA levels. Overall, men with normal PSA levels who undergo RP represent a favorable risk group.

Aged↗