Prostate specific antigen best practice statement: 2009 update.

PURPOSE: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection. MATERIALS AND METHODS: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases. RESULTS: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities. CONCLUSIONS: Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

Prostate specific antigen best practice statement: 2009 update.

PURPOSE: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection. MATERIALS AND METHODS: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases. RESULTS: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities. CONCLUSIONS: Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

Comparison of cancers detected at only a sextant or alternative location.

OBJECTIVES: To evaluate the effect of the tumour-positive biopsy site at extended biopsy on tumour volume and potential biological significance of prostate cancer. PATIENTS AND METHODS: We retrospectively evaluated radical prostatectomy specimens from 247 consecutive men diagnosed with prostate cancer by extended biopsy. Men who had both a positive sextant and alternative site were excluded, resulting in 132 evaluable men. We assessed age, pretreatment prostate-specific antigen (PSA) level, prostate volume, pathological stage, Gleason score, total tumour volume, and location (sextant or alternative site) of the positive biopsy. Patients were grouped by location of the positive biopsy, i.e. sextant site only or alternative site only, including anterior horn, midline region and transition zone. RESULTS: A biopsy from a sextant-only or an alternative site only was positive in 42% (56/132) and 58% (76/132) of men, respectively. There was no significant difference in PSA level, number of positive cores, pathological stage, Gleason score, total tumour volume or the incidence of low-volume/low-grade cancer (volume <0.5 mL and a Gleason score of

Obesity, weight gain, and risk of biochemical failure among prostate cancer patients following prostatectomy.

PURPOSE: Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis, especially in tumor progression. The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index (BMI) as a measure of obesity. EXPERIMENTAL DESIGN: We carried out a prospective study of 526 patients registered at the M.D. Anderson Cancer Center from 1992 to 2001. Kaplan-Meier and Cox proportional hazard analyses were done. RESULTS: During an average follow-up of 54 months, 97 (18%) post-prostatectomy patients experienced biochemical failure. Patients who were obese (BMI > or = 30 kg/m2) at diagnosis had a higher rate of biochemical failure than nonobese men (P = 0.07). Those obese at 40 years had an even greater rate of biochemical failure (P = 0.001). Higher BMI at diagnosis [hazard ratio (HR), 1.07; P = 0.01] and Gleason score = 7(4 + 3) and > or =8 (HR, 3.9; P = 0.03 and HR, 10.0; P < or = 0.001, respectively) remained significant independent predictors of biochemical failure in multivariate analysis. Men who gained weight at the greatest rate (>1.5 kg/y) between 25 years and diagnosis progressed significantly sooner (mean time, 17 months) than those who exhibited a slower weight gain (mean time, 39 months; P(trend) = 0.005). The inclusion of obesity to the clinical nomogram improved performance. CONCLUSIONS: Our findings validate the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited.

Demographic and past screening behaviors of men attending a free community screening program for prostate cancer.

This study characterizes demographic and past prostate screening behaviors of men who participated in a free screening for prostate cancer. Demographics, past prostate screening behavior, perceived risk, and cancer worry were assessed in 1,680 men. Mean age was 58.2 years, 56% were White, and 76% had health insurance. Men with insurance were more likely to have had a previous prostate-specific antigen (PSA) test and digital rectal exam (DRE). White men were more likely to have had a previous PSA and DRE and to have discussed PSA testing with a physician than African American men. African American men reported greater perceived risk and more worry than White men. Screening differences between African American and White men were explained by insurance status. These results may help guide the development of and promotion for future screening programs. Future efforts should be directed at increasing awareness about screening procedures for prostate cancer.

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer.

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.

Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy.

BACKGROUND: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. PATIENTS AND METHODS: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. RESULTS: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA < or = 0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. CONCLUSION: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal treatment. We further suggest that salvage radiotherapy should be given early when the PSA is still low.

Management of Stages I and II Nonseminomatous Germ Cell Tumors of the Testis.

Management of Stages I and II nonseminomatous tumors of the testis is in a state of flux as a result of improvement in the major modalities for patient treatment. Both radiotherapy and retroperitoneal lymphadenectomy, used alone, are providing five-year survival rates in the range of 75 to 90% for patients with localized disease (Stage 1). However, since current staging methods fail to detect regional disease (Stage II) in 15 to 20% of the patients before therapy, lymphadenectomy provides a distinct and additional advantage, both by removing possible unseen metastases and by determining pathologically which patients may benefit from adjuvant therapy. Both surgery and radiotherapy, when used alone to combat extensive retroperitoneal disease, have proved unsatisfactory; surgery is frequently difficult or impossible, and persistent disease is common following radiotherapy. Therefore, patients with extensive Stage II disease are best treated with either preoperative chemotherapy or preoperative radiotherapy (2500 to 3000 rads over three to four weeks) before resection of the retroperitoneal disease. The benefits of adjuvant chemotherapy for patients with Stages I and II disease is under continuing investigation.

Cancer worry is associated with abnormal prostate-specific antigen levels in men participating in a community screening program.

An accumulating body of research suggests that psychological factors can affect physiological parameters. We assessed the association between the perceived risk of prostate cancer, prostate cancer-specific worry, and cancer-related symptoms and prostate-specific antigen (PSA) levels or the findings from digital rectal examination (DRE) in a large sample of men undergoing a free prostate cancer screening. Participants (n = 1635) completed a background questionnaire and a questionnaire that assessed their prostate cancer history, screening behavior, perceived risk of prostate cancer, and prostate cancer worry. PSA levels were then determined, and a DRE was conducted. A PSA level of >or=4.0 ng/ml was considered abnormal. The sample size for the multivariate analyses was reduced because of missing data on certain items. Participants who had an abnormal PSA level reported a significantly higher perceived cancer risk (P = 0.02), cancer worry (P = 0.004), and a greater percentage indicated the reason for the current screening was cancer-related symptoms (P = 0.014) than did participants who had normal PSA levels. Multivariate logistic regression analyses controlling for age, past screening behavior, past screening results, and reason for current screening revealed that perceived cancer risk [P = 0.01; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], cancer worry (P = 0.001; OR, 3.3; 95% CI, 1.7-6.5), and cancer-related symptoms (P = 0.05; OR, 3.4; 95% CI, 1.1-10.3) remained significantly associated with an abnormal PSA level. When perceived cancer risk, cancer worry, and cancer-related symptoms were entered in the same multivariate analysis, only cancer worry remained in the model. The present findings suggest that prostate cancer-specific worry was associated significantly with an abnormal PSA level.

Cavernous nerve reconstruction to preserve erectile function following non-nerve-sparing radical retropubic prostatectomy: a prospective study.

Erectile dysfunction following radical prostatectomy for treatment of clinically localized prostate cancer remains a problem that deters many men from seeking surgical treatment. Sparing the cavernous nerves has been popularized as a method of preserving potency, but men with locally advanced disease may be at increased risk for positive margins with this technique. In this study, sural nerve grafting of the cavernous nerve bundles, to preserve postoperative potency while potentially maximizing cancer control, was examined. Thirty men were enrolled in this prospective phase I study and underwent non-nerve-sparing radical prostatectomy performed by one of two protocol surgeons. Preoperative erectile function was assessed both objectively, using a RigiScan (Timm Medical Technologies, Inc., Eden Prairie, Minn.), and subjectively. The cavernous nerves were identified and resected during the operation with the use of an intraoperative mapping device (CaverMap; Alliant Medical Technologies, Norwood, Mass.). Bilateral autologous sural nerve grafting to the cavernous nerve stumps was performed by one of two protocol plastic surgeons. Postoperative erectile dysfunction therapy, using intracorporeal injection, a vacuum pump, and/or oral sildenafil therapy, was instituted 6 weeks after the operation. Spontaneous erectile activity was subjectively and objectively measured every 3 months after the operation. Follow-up periods ranged from 13 to 33 months (mean, 23 months). Overall, 18 of 30 patients (60 percent) demonstrated both objective and subjective evidence of spontaneous erectile activity. Of those 18 men, 13 (72 percent) were able to have intercourse (seven unassisted and six with the aid of sildenafil). No disease or biochemical recurrences have been noted in this group of patients with locally advanced disease. In conclusion, autologous sural nerve grafting after non-nerve-sparing radical prostatectomy is an effective means of preserving spontaneous erectile activity after the operation while maximizing cancer control potential.

The effects of a presurgical stress management intervention for men with prostate cancer undergoing radical prostatectomy.

PURPOSE This study assessed the short-term and long-term efficacy of a presurgical stress management intervention at reducing mood disturbance and improving quality of life (QOL) in men undergoing radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS One hundred fifty-nine men were randomly assigned to a two-session (plus two boosters) presurgical stress management intervention (SM), a two-session (plus two boosters) supportive attention group (SA), or a standard care group (SC). Assessments occurred 1 month before surgery; 1 week before surgery; the morning of surgery; 6 weeks after surgery, and 6 and 12 months after surgery. Results Results indicated significant group differences in mood disturbance before surgery (P = .02), such that men in the SM group had significantly less mood disturbance than men in the SC group (P = .006), with no significant differences between the SM and SA or SA and SC groups. In the year after surgery, there were significant group differences on Medical Outcomes Study 36-item short form survey (SF-36) physical component summary (PCS) scores (P = .004); men in the SM group had significantly higher PCS scores than men in the SC group (P = .0009), and there were no significant differences between the SM and SA or SA and SC groups. There were no group effects on prostate-specific QOL or SF-36 mental health scores. CONCLUSION These findings demonstrate the efficacy of a brief presurgical stress management intervention in improving some short-term and long-term outcomes. If these results are replicated, it may be a useful adjunct to standard care for men with prostate cancer undergoing surgery.

A randomized prospective trial evaluating testosterone, haemoglobin kinetics and quality of life, during and after 12 months of androgen deprivation after prostatectomy: results from the Postoperative Adjuvant Androgen Deprivation trial.

OBJECTIVE: To assess testosterone and haemoglobin kinetics in the Postoperative Adjuvant Androgen Deprivation (PAAD) trial, and correlate these with quality of life (QoL) in this prospective randomized study. PATIENTS AND METHODS: Forty-three patients met the criteria for high-risk cancer after RRP (Gleason score > or = 8, pT3c or Gleason score 7 concomitant with pT3a/b and positive surgical margins) and were prospectively randomized to either observation or AD for 12 months. Haemoglobin and testosterone levels were determined and QoL surveyed at regular intervals for 24 months. RESULTS: Serum testosterone levels were castrate in 19 of 21 treated patients at 3 months and all at 6 months after starting AD. Levels failed to return to normal at 6 months after stopping treatment in six of 16 (38%) patients, and at 12 months in three of 17 (18%). AD caused a delay in the recovery of haemoglobin levels to normal after RRP. There was no statistically significant decline in the Short Form-36 QoL score with AD. Scores on the University of California-Los Angeles Sexual Functioning Scale were decreased during AD, but returned to a level not statistically significantly different from controls after stopping treatment. CONCLUSION: A year of adjuvant AD after RRP affected serum haemoglobin, testosterone and sexual function reversibly, with return to control levels within the subsequent year in most patients. No significant effect on overall QoL with AD was detected in the study.

Impact of fellowship training on pathologic outcomes and complication rates of radical prostatectomy.

BACKGROUND: The study was conducted to assess the results of radical prostatectomy (RP) performed by fellowship-trained surgeons in the first year of independent practice. METHODS: A prospective cohort study of 66 men who underwent RP performed by 2 recently graduated fellowship-trained surgeons (C.J.R., n = 27; A.M.K., n = 39) in their first year of independent practice was undertaken. Preoperative, operative, and postoperative data were collected and analyzed. Median follow-up of the cohort is 12.5 months. RESULTS: The median patient age was 61.2 +/- 6.9 years (range, 44-74 years), the median prostate-specific antigen level was 5 ng/mL (range, 1.2-39.4 ng/mL), and the median prostate biopsy-determined Gleason score was 7. Of the 66 men, 25 (38%) underwent a bilateral nerve-sparing RP, 20 (30%) underwent a unilateral nerve-sparing RP, and 21 (32%) underwent a nonnerve-sparing procedure. Forty-two men (63%) underwent a pelvic lymph node dissection. The median operative time was 201 minutes. Median estimated blood loss was 734 mL (range, 300-1600 mL). There were 4 major complications--a pulmonary embolism in 3 patients and an intraoperative rectal injury in 1. Pathologic classification was as follows: pT2, 74%; pT3a, 23%; pT3b, 2%; and pN+, 2%. The positive margin rate was 14% overall and only 2% in men with pT2 disease. CONCLUSIONS: Results of RP performed by fellowship-trained surgeons in their first year of practice compare favorably with results of RP in a large series reported by more experienced surgeons. Being trained in an environment where an experienced surgeon serves as first assistant to the trainee appears to abbreviate the learning curve associated with this procedure.

African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men.

BACKGROUND: Although prostate cancer (PC) mortality disproportionately affects African-American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c). METHODS: The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate-specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software. RESULTS: For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score > or =7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (> or =7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001). CONCLUSIONS: Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men.

Efficacy of prostatic fossa biopsy in detecting local recurrence after radical prostatectomy.

OBJECTIVES: To evaluate retrospectively the efficacy of prostatic fossa biopsy in detecting local recurrence of prostate cancer in men with biochemical failure after radical prostatectomy. METHODS: Between January 1997 and December 2002, 100 men without prior adjuvant therapy after radical prostatectomy underwent transrectal ultrasound (TRUS)-guided biopsy of the prostatic fossa. The TRUS findings, digital rectal examination (DRE) findings, serum total prostate-specific antigen (PSA) level at TRUS, PSA velocity, and pathologic stage and Gleason score of the radical prostatectomy specimen were correlated with the biopsy results. RESULTS: Overall, 29 (29%) of the 100 men who underwent biopsy had documented local recurrence. The sensitivity and specificity of DRE to detect biopsy-proven local recurrence was 72.4% and 64.8%, respectively. The corresponding values for TRUS were 86.2% and 53.5%. None of the men with a serum PSA concentration of less than 0.5 ng/mL at biopsy who had normal results for both TRUS and DRE had a biopsy-proven local recurrence. By stepwise multivariate logistic regression analysis, abnormal TRUS findings and serum PSA concentration at biopsy were independent predictors for positive fossa biopsy results. The combination of TRUS and serum PSA concentration was the best predictive model for a positive fossa biopsy result. CONCLUSIONS: Prostatic fossa biopsy should be avoided in patients with both or either normal DRE or TRUS findings when the PSA level is less than 0.5 ng/mL.

Relationship between plasma carotenoids and prostate cancer.

Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of > or =7, n = 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of alpha-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.

Prostate cancer early detection clinical practice guidelines in oncology.

Because guidelines for the early detection of prostate cancer were developed by the ACS in the early 1990s, many variants of the total PSA assay have been introduced in attempts to increase the sensitivity of screening programs (cancer detection) while maintaining their specificity (elimination of unnecessary biopsies). Again, it is important to note that the NCCN guidelines recommend a method by which individuals and their physicians can use these new methods rationally for the early detection of prostate cancer. These guidelines are not designed to provide an argument for the use of early detection programs for prostate cancer. Rather, they are meant to provide a vehicle by which early detection efforts can be practiced in an evidence-based, systematic fashion in patients who choose to participate in such programs. The NCCN guidelines incorporate many new validated findings in addition to the DRE and PSA test. These new factors include percent-free PSA, PSA velocity, PSA testing intervals, biopsy pathology, and TRUS-guided biopsy techniques. The panel will re-examine the clinical utility of these new modalities annually and the guidelines will be modified accordingly. In addition, future iterations of these guidelines may incorporate new serum markers currently undergoing clinical investigation. It is the hope of the NCCN and this guideline panel that these algorithms will achieve the goal of assisting patients and clinicians who are choosing a program of early detection for prostate cancer to make decisions regarding the need for prostate biopsy. Any clinician who uses these guidelines is expected to exercise independent medical judgment in the context of the individual clinical circumstances to determine the patient's need for prostate biopsy. These guidelines will continue to evolve as the field of prostate cancer advances.

Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case-control analysis.

Oxidative damage is an important factor in prostate carcinogenesis, and overexpression of human MutT homolog (hMTH), a repair gene that removes oxidative damage, is a molecular marker of cellular oxidative stress. Therefore, we tested the hypothesis that overexpression of hMTH in unaffected (normal) surrogate tissue is associated with risk of prostate cancer in a pilot study of 51 patients with diagnosed prostate cancer and 50 age- and ethnicity-matched controls. Total RNA was extracted from phytohemagglutinin-stimulated peripheral blood lymphocytes of these subjects. We performed the real-time reverse transcription-polymerase chain reaction assay to evaluate the relative mRNA expression of three oxidative-damage-repair genes, human MutM homolog (hMMH), hMTH, and human MutY homolog (hMYH), with beta-actin and human O(6)-methylguanine DNA methyltransferase (hMGMT) as the internal controls. The relative gene expression levels of hMMH and hMTH were borderline higher in the cases than in controls (15.3% and 28.8% higher, respectively; P = 0.046 and P = 0.035, respectively), whereas no increase was observed for hMYH and hMGMT. With the median of the controls' values as the cutoff point, we observed that a high expression level of hMTH, but not of other genes, was associated with a significantly increased risk of prostate cancer (odds ratio = 2.62; 95% confidence interval = 1.13-6.75) after adjustment for age and ethnicity. These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. Although our findings were biologically plausible and consistent with the literature, they were preliminary and need to be confirmed in larger studies. In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well.

Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy.

PURPOSE: Radical prostatectomy (RP) is a highly effective treatment for patients with prostate cancer. However, patients with positive surgical margins after radical prostatectomy have less than ideal outcomes with 5-year progression rates between 36% and 50%. Postoperative radiation therapy (RT) is often advocated for improving these outcomes. We identified predictors of response to adjuvant RT given for positive margins after RP. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of men who underwent RP between 1987 and 1999 at our institution and who received adjuvant RT for positive surgical margins. Only patients in whom prostate specific antigen (PSA) was undetectable after RP as well as before the initiation of RT were included. Numerous clinicopathological variables, including pre-RP PSA, pathological stage, margin length and location, and extracapsular extension or seminal vesicle involvement, were assessed for their adverse effect on the biochemical recurrence rate after adjuvant RT. RESULTS: A total of 62 men met our inclusion criteria. Median age at surgery was 60.7 +/- 6.1 years and median PSA at presentation was 9.0 ng/ml (range 1.4 to 64.9). The median RT dose was 60.0 +/- 3.6 Gy. RT was started a median of 5.0 +/- 3.6 months after RP. The 5 and 10-year biochemical disease-free survival rates for the whole group were 90.2% and 87.9%, respectively. Of all parameters tested only Gleason score 4 + 3 or greater (p = 0.037) and pre-RP PSA greater than 10.9 ng/ml (p = 0.040) were predictive of biochemical recurrence after adjuvant RT on univariate analysis. On multivariate analysis only pre-RP PSA greater than 10.9 ng/ml remained an independent predictor (p = 0.031). CONCLUSIONS: In the setting of true adjuvant RT in patients with positive margins after RP and undetectable PSA those with predominant Gleason grade 4 or greater, or PSA greater than 10.9 ng/ml at presentation are at increased risk for recurrence after adjuvant RT.