Dermatologic Toxicities: A Chart Review of Clinical Management Among Patients With Metastatic Colorectal Cancer Treated With Panitumumab.

BACKGROUND: At least 90% of patients with metastatic colorectal cancer (mCRC) who are treated with an anti-EGFR will develop a dermatologic toxicity. Preemptive management strategies have been shown to reduce the severity of rash. OBJECTIVES: This article aims to describe treatment modalities used for the management of dermatologic toxicity among patients with mCRC who were treated with panitumumab and to assess the proportion of patients who were recommended preemptive versus reactive management strategies. METHODS: This retrospective chart review evaluated different treatment modalities and routes of administration. The modalities were categorized as prescription or over-the-counter. The timing in relation to the first dose of panitumumab was used to define preemptive versus reactive treatments. FINDINGS: In a sample of 330 patients, only 10% of patients were recommended to begin treatment for rash preemptively. The two most common treatment modalities for preemptively and reactively treated patients were prescription oral antibiotics and prescription topical antibiotics.

Associations Between iCOGS Single Nucleotide Polymorphisms and Upgrading in Both Surgical and Active Surveillance Cohorts of Men with Prostate Cancer.

BACKGROUND: Associations have been documented recently between some of the 23 single nucleotide polymorphisms newly discovered with the Collaborative Oncological Gene-environment Study iCOGS array that indicate prostate cancer (PCa) risk and aspects of disease aggressiveness. The utility of these iCOGS SNPs remains to be determined in active surveillance (AS). OBJECTIVE: To determine associations between iCOGS SNPs and upgrading among men who underwent surgical treatment and AS for low-risk PCa. DESIGN, SETTING, AND PARTICIPANTS: The genotypes of the 23 iCOGS SNPs were determined for all white subjects with biopsy Gleason score (GS) 6 including 950 men who underwent definitive treatment with surgery and 209 men who elected AS. The clinical and pathologic characteristics were documented for all subjects. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Men who underwent surgery were grouped according to their pathologic GS (upgraded was defined as GS ≥7; nonupgraded remained GS 6). Men who were enrolled in AS were also grouped according to their GS on subsequent surveillance biopsies. Statistical analyses were performed comparing the genotypes between the upgraded and nonupgraded groups. RESULTS AND LIMITATIONS: Overall, 31% and 34% of men were upgraded in the surgery and AS cohorts, respectively. Three iCOGS SNPs were significantly associated with the risk of upgrading in the surgical cohort. After correction for multiple testing, only rs11568818 on chromosome 11q22 remained significantly associated with upgrading. Assessment of this allele in the AS cohort reveals that it was present at noteworthy higher frequencies in men with high-grade disease on surveillance biopsies compared with nonupgraded men (p=0.003). This study was primarily limited by the homogeneous patient population. CONCLUSIONS: This is the first report of a SNP on chromosome 11q22 associated with higher grade disease in a surgical cohort that is also validated for eventual upgrading in a prospective AS cohort. PATIENT SUMMARY: We examined the relationship between a group of genetic markers and prostate cancer (PCa) aggressiveness in a group of patients who underwent surgery for PCa and a group of patients who were enrolled in active surveillance. We found that these genetic markers helped predict which patients had more aggressive disease in both groups.

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.

Persistent organic pollutants and early menopause in U.S. women.

OBJECTIVE: Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. METHODS: Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years. FINDINGS: This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of ß-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. CONCLUSIONS: This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

State-mandated insurance coverage is associated with the approach to hydrosalpinges before IVF.

The aim of this study was to determine whether practice in states with infertility insurance mandates is associated with physician-reported practice patterns regarding hydrosalpinx management in assisted reproduction clinics. A cross-sectional, internet-based survey of 442 members of Society for Reproductive Endocrinology and Infertility or Society of Reproductive Surgeons was performed. Physicians practising in states without infertility insurance mandates were more likely to report performing diagnostic surgery after an inconclusive hysterosalpingogram than physicians practising in states with mandates (RR 1.2, 95% CI 1.1-1.3, P < 0.01). Additionally, respondents in states without mandates were more likely to report that, due to lack of infertility insurance coverage, they did not perform salpingectomy (SPX) or proximal tubal occlusion (PTO) before assisted reproduction treatment (RR 1.4, 95% CI 1.1-1.8, P = 0.01). Finally, respondents in states without mandates were less likely to report that the presence of assisted reproduction treatment coverage determined the urgency with which they pursued SPX or PTO before treatment (RR 0.7, 95% CI 0.5-1.0, NS). These results persisted after controlling for physician years in practice, age and clinic volume. In conclusion, self-reported physician practice interventions for hydrosalpinges before assisted reproduction treatment may be associated with state-mandated infertility insurance. Fallopian tube dysfunction is a known cause of infertility and severe dysfunction is manifested by dilation and occlusion, known as hydrosalpinx. Outcomes with assisted reproductive techniques (ART) are lower when hydrosalpinges are present and while there are several theories for this, reproductive specialist recommend "neutralizing" the tube either by occlusion or removal in order to enhance pregnancy rates. In the United States, coverage for infertility services is not uniform with only 15 states having some legislation requiring infertility benefits. Some states where ART is covered liberally, physicians might have different practice patterns related to the neutralization of hydrosalpinges compared to those who are in non -mandated states. We utilized a survey of over 400 providers in the United States to examine their practice patterns as it relates to hydrosalpinges based on which state they practice in and whether or not that state has mandated coverage of not.

Genetically adjusted prostate-specific antigen values may prevent delayed biopsies in African-American men.

OBJECTIVE: To evaluate whether genetic correction using the genetic variants prostate-specific antigen (PSA)-single nucleotide polymorphisms (SNPs) could reduce potentially unnecessary and/or delayed biopsies in African-American men. SUBJECTS AND METHODS: We compared the genotypes of four PSA-SNPs between 964 Caucasian and 363 African-American men without known prostate cancer (PCa). We adjusted the PSA values based on an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥ 2.5 or ≥ 4.0 ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who were below and above the biopsy threshold after genetic correction, respectively. RESULTS: Overall, 349 (96.1%) and 354 (97.5%) African-American men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in African-American men did not avoid any potentially unnecessary biopsies, but resulted in a significant (P < 0.001) reduction in potentially delayed biopsies by 2.5% and 3.9%, based on the biopsy threshold level. CONCLUSIONS: There are significant differences in the influence of the PSA-SNPs between African-American and Caucasian men without known PCa, as genetic correction resulted in an increased proportion of African-American men crossing the threshold for biopsy. These results raise the question of whether genetic differences in PSA might contribute to delayed PCa diagnosis in African-American men.

Normal first stage of preterm labor.

OBJECTIVE: To compare first-stage labor patterns in women in preterm labor to those in labor at term. STUDY DESIGN: We performed a retrospective cohort study of consecutive women admitted from 2004 to 2008 with viable (≥ 24 weeks) vertex singleton gestations who reached the second stage of labor. Labor curves for preterm and term labor were created using a repeated-measures analysis with polynomial modeling. Interval-censored regression was used to estimate and compare median time of progression of labor. Multivariable analyses were performed to adjust for smoking, obesity (body mass index ≥ 30), induction, and nulliparity. The adjusted model was stratified by parity and induction of labor. RESULTS: Of 5,612 consecutive births, 224 were preterm (<37 weeks) and 5,388 were term (≥ 37 weeks). Preterm first-stage labor progressed significantly faster than term labor (median time 4 to 10 cm: 3.3 hours versus 4.5 hours, p < 0.01). When stratified by parity, preterm labor progressed significantly more rapidly than term labor in both nulliparous and multiparous women (median time 4 to 10 cm: 3.7 hours versus 4.9 hours [p = 0.04] in nulliparous women and 2.5 hours versus 4.3 hours [p = 0.01] in multiparous women). CONCLUSION: Women in preterm labor progress more rapidly through the first stage of labor than women at term.

Prostate cancer risk alleles are associated with prostate cancer volume and prostate size.

PURPOSE: Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume. MATERIALS AND METHODS: The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes. RESULTS: On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively). CONCLUSIONS: Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence.

Interval from loop electrosurgical excision procedure to pregnancy and pregnancy outcomes.

OBJECTIVE: Previous studies have shown mixed results for pregnancy outcomes after loop electrosurgical excision procedure (LEEP); however, evidence is lacking regarding the pregnancy outcome of spontaneous abortion with respect to time elapsed from LEEP to pregnancy. We investigated risks of spontaneous abortion and preterm birth as they relate to time elapsed from LEEP to pregnancy. METHODS: A 10-year, multicenter cohort study of women who underwent LEEP was performed between 1996 and 2006. Trained research nurses conducted telephone interviews with all patients to complete data extraction unavailable in charts. Median time from LEEP to pregnancy for spontaneous abortion compared with no spontaneous abortion and preterm birth before 34 and before 37 weeks of gestation compared with term birth were estimated. Patients with time intervals less than 12 months compared with 12 months or more from LEEP to pregnancy were then compared with identify adjusted odds ratios for spontaneous abortion and preterm birth. RESULTS: Five hundred ninety-six patients met inclusion criteria. Median time from LEEP to pregnancy was significantly shorter for women with a spontaneous abortion (20 months [interquartile range 11.2-40.9] compared with 31 months [interquartile range 18.7-51.2]; P=.01) but did not differ for women with a term birth compared with preterm birth. Women with a time interval less than 12 months compared with 12 months or more were at significantly increased risk for spontaneous abortion (17.9% compared with 4.6%; adjusted odds ratio 5.6; 95% confidence interval 2.5-12.7). No increased risk was identified for preterm birth before 34 weeks of gestation or before 37 weeks of gestation. CONCLUSION: Women with a shorter time interval from LEEP to pregnancy are at increased risk for spontaneous abortion but not preterm birth. LEVEL OF EVIDENCE: : II.

Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that use of the Foley bulb plus vaginal misoprostol will result in shorter induction-to-delivery time compared with vaginal misoprostol alone. METHODS: We randomized 123 women undergoing induction of labor with singleton pregnancies at 24 weeks of gestation or greater with an unfavorable cervix (Bishop score 6 or lower) to Foley bulb plus vaginal misoprostol (n=56) or vaginal misoprostol alone (n=61). Women with fetal malpresentation, multifetal gestation, spontaneous labor, contraindication to prostaglandins, nonreassuring fetal heart rate tracing, intrauterine growth restriction, anomalous fetus, fetal demise, or previous cesarean delivery or other significant uterine surgery were excluded. The primary outcome measure was induction-to-delivery time. Secondary outcomes were mode of delivery, tachysystole with fetal decelerations, terbutaline use, postpartum hemorrhage, chorioamnionitis, neonatal Apgar scores, and neonatal intensive care unit admission. Analysis followed the intention-to-treat principle. RESULTS: The mean induction-to-delivery time was shorter with the combination of the Foley bulb and vaginal misoprostol when compared with vaginal misoprostol alone (15.3±6.5 compared with 18.3±8.7 hours, difference -3.1 hours, 95% confidence interval [CI] -5.9 to -0.30). The combination also resulted in shorter induction to complete cervical dilation time (13.7±5.9 compared with 17.1±8.7 hours, difference -3.5 hours, 95% CI -6.7 to -0.4). There were no differences in labor complications or adverse neonatal and maternal outcomes. CONCLUSION: A combination of the Foley bulb and vaginal misoprostol resulted in a shorter induction-to-delivery time when compared with vaginal misoprostol alone without increasing labor complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01279343. LEVEL OF EVIDENCE: I.

Personalized prostate specific antigen testing using genetic variants may reduce unnecessary prostate biopsies.

PURPOSE: Recent studies have identified genetic variants associated with increased serum prostate specific antigen concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on prostate specific antigen, it may be possible to create a personalized prostate specific antigen cutoff to more accurately identify individuals for whom biopsy is recommended. Therefore, we determined how many men would continue to meet common biopsy criteria after genetic correction of their measured prostate specific antigen concentrations. MATERIALS AND METHODS: The genotypes of 4 single nucleotide polymorphisms previously associated with serum prostate specific antigen levels (rs2736098, rs10788160, rs11067228 and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk. Analyses were used to compare the percentage of men who would meet commonly used biopsy thresholds (2.5 ng/ml or greater, or 4.0 ng/ml or greater) before and after genetic correction. RESULTS: Genetic correction of serum prostate specific antigen results was associated with a significantly decreased percentage of men meeting biopsy thresholds. Genetic correction could lead to a 15% or 20% relative reduction in the total number of biopsies using a biopsy threshold of 2.5 ng/ml or greater, or 4.0 ng/ml or greater, respectively. In addition, genetic correction could result in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses. CONCLUSIONS: Our results suggest that 4 single nucleotide polymorphisms can be used to adjust a man's measured prostate specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.

Risk of cesarean delivery after loop electrosurgical excision procedure.

OBJECTIVE: To estimate whether previous loop electrosurgical excision procedure (LEEP) affects the risk of cesarean delivery. METHODS: A secondary analysis of a multicenter retrospective cohort study was performed. Women who underwent a prior LEEP were compared with two unexposed cohorts: 1) women with prior screening cervical cytology only; and 2) women with prior cervical punch biopsy. The pregnancy evaluated in this analysis was the first pregnancy of a duration more than 20 weeks of gestation after the identifying cervical procedure. Stratified and multivariable logistic regression analyses were used to control for confounding. RESULTS: Five hundred ninety-eight women with prior LEEP, 588 women with screening cytology only, and 552 women with cervical biopsy were included in this study. After adjusting for relevant confounders, similar rates of cesarean delivery were seen in women with prior LEEP (31.6%) and women with prior cervical cytology only (29.3%, adjusted odds ratio [OR] 1.06, 95% confidence interval [CI] 0.79-1.41). Likewise, no differences were found in rates of cesarean delivery when women with prior LEEP were compared with those with a prior punch biopsy (29.0%, adjusted OR 0.99, 95% CI 0.74-1.33). Among women who had a cesarean delivery, arrest of labor was the indication for cesarean delivery in a similar proportion of women in the groups (LEEP compared with cytology only, P=.12; LEEP compared with biopsy, P=.50). Loop electrosurgical excision procedure specimen size did not vary by delivery mode. Length of time between LEEP and subsequent pregnancy also did not influence delivery mode. CONCLUSION: Loop electrosurgical excision procedure does not affect mode of delivery in the subsequent pregnancy. LEVEL OF EVIDENCE: II.

Neural tube defects and associated low birth weight.

OBJECTIVE: To estimate the association between neural tube defects (NTDs) and low birth weight. STUDY DESIGN: This was a retrospective cohort study of women undergoing ultrasound from 17 to 22 weeks from 1990 to 2008. Presence or absence of fetal NTD defined the two study groups. The primary outcomes were intrauterine growth restriction (IUGR), birth weight <10th percentile, and severe IUGR <5th percentile. Subgroup analysis was performed to observe if the association with IUGR persisted. RESULTS: Of 66,956 women, 170 were found to have fetal NTD. Only the rate of advanced maternal age differed between the study groups. Fetuses with an NTD were at significantly increased risk for IUGR <10th percentile (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.8 to 3.9) and <5th percentile (aOR 2.8, 95% CI 1.9 to 4.3). The association persisted in subgroup analyses. CONCLUSION: Fetuses with NTD are at increased risk for IUGR, suggesting that a policy of serial growth scans in cases with isolated NTD is justified.

Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer.

OBJECTIVE: • To determine whether the prostate-specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life-threatening tumours. PATIENTS AND METHODS: • From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening-study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer. • The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2). • We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen-detected and high-grade prostate cancer. RESULTS: • The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001). • After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2-fold increased risk of prostate cancer (95% confidence interval 7.0-9.6, P < 0.001) and 5.4-fold increased risk of Gleason score 8-10 prostate cancer on biopsy. • Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high-grade prostate cancer (net reclassification, P < 0.001). CONCLUSIONS: • Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high-grade disease. • Compared with men with a risk count of ≤1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8-fold increased risk of prostate cancer and 5.4-fold increased risk of Gleason 8-10 disease on biopsy, adjusting for age and PSA level. • Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low-risk prostate cancer.

Correlation between serum prostate-specific antigen and cancer volume in prostate glands of different sizes.

OBJECTIVES: To further evaluate the relationship of prostate-specific antigen (PSA) with prostate size and tumor volume in a contemporary surgical series. Although early studies showed a strong correlation between PSA and tumor volume, it has been suggested that PSA is no longer a valid marker for prostate cancer and only correlates with prostate size. METHODS: From 2003 to 2009, 1234 men with data on prostate weight and total tumor volume underwent radical prostatectomy by a single surgeon. Prostate size was classified into tertiles: small (≤ 41.2 g), medium (41.3-54.5 g), and large (≥ 54.6 g). Pearson correlation coefficients were used to examine the relationship of PSA with prostate size and tumor volume across different prostate sizes. RESULTS: Median preoperative PSA was 4.9 ng/mL (standard deviation ± 4.6), mean prostate size was 51.7 g, and mean tumor volume was 5.6 cm(3). PSA had a significant correlation with prostate size only at a prostate weight ≥ 54.6 g (P = .02). Regardless of prostate size, PSA had a more robust significant correlation with tumor volume than with prostate size (all P < .0001). CONCLUSIONS: PSA was significantly correlated with prostate size only in the largest prostate glands, but was significantly associated with tumor volume in small, medium, or large prostates. Thus, PSA continues to be a better marker for tumor volume than for prostate size.

Preoperative prostate specific antigen doubling time is not a useful predictor of biochemical progression after radical prostatectomy.

PURPOSE: Postoperative prostate specific antigen doubling time may be used as a surrogate for prostate cancer specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the usefulness of preoperative prostate specific antigen doubling time for the initial prediction of prostatectomy outcomes. MATERIALS AND METHODS: Preoperative prostate specific antigen doubling time was calculated in 1,208 men from a large prostate cancer screening study who were treated with radical prostatectomy. We examined the relationship of prostate specific antigen doubling time with tumor features and biochemical progression-free survival. RESULTS: Overall prostate specific antigen doubling time was associated with nonorgan confined disease (OR 0.996, 95% CI 0.992-0.999, p = 0.013) but not with biochemical progression (HR 1.000, 95% CI 0.998-1.001, p = 0.66). Using previously published 18 and 36-month thresholds for prostate specific antigen doubling time there was no significant relationship between doubling time and specific adverse pathological features or biochemical progression. Using the concordance index prostate specific antigen doubling time did not enhance the prediction of biochemical progression beyond that achieved by a model with prostate specific antigen, clinical stage and biopsy Gleason score. CONCLUSIONS: In our series of men with newly diagnosed, clinically localized prostate cancer shorter preoperative prostate specific antigen doubling time was associated with nonorgan confined disease but not with biochemical progression after radical prostatectomy. All calculations of prostate specific antigen kinetics may not be equivalent. Caution should be exercised when using prostate specific antigen doubling time in the pretreatment setting.

Can prostate specific antigen velocity thresholds decrease insignificant prostate cancer detection?

PURPOSE: A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer. MATERIALS AND METHODS: A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume. Insignificant cancer was defined by the Ohori criteria as organ confined, tumor volume 0.5 cc or less and no primary or secondary Gleason pattern 4 or 5. We calculated the proportion of men with pathologically insignificant prostate cancer stratified by prostate specific antigen velocity. RESULTS: Preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year was significantly associated with high grade disease (p = 0.008), positive surgical margins (p = 0.003) and seminal vesicle invasion (p = 0.007) at radical prostatectomy. Median tumor volume was also significantly higher in men with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year (3.1 vs 2.4 cc, p = 0.0001). Overall 69 men (6%) met the Ohori criteria for insignificant cancer. Patients with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year were 50% less likely to have insignificant disease (10% vs 5%, p = 0.003). CONCLUSIONS: A prostate specific antigen velocity threshold of 0.4 ng/ml per year was associated with the likelihood of insignificant prostate cancer. This suggests that prostate specific antigen velocity may be a useful adjunct in prostate cancer screening to increase specificity for identifying patients with clinically significant disease.

Treatment outcomes of radical prostatectomy in potential candidates for 3 published active surveillance protocols.

OBJECTIVES: To examine the treatment outcomes of men who would have been eligible for active surveillance (AS) but underwent immediate radical retropubic prostatectomy (RRP). AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer (PCa). METHODS: From a prospective RRP database, we evaluated the tumor features and treatment outcomes for men who would have met 1 of 3 published AS criteria: (1) clinically localized disease, Gleason < or = 7, and no significant comorbidities (Patel et al, J Urol. 2004;171:1520-1524) (2) T1b-T2b N0M0 disease, Gleason < or = 7, and prostate-specific antigen < or = 15 ng/mL (Choo R et al. J Urol. 2002;167:1664-1669), or (3) T1c PCa (Mohler JL et al. World J Urol. 1997;15:364-368.). RESULTS: 3959, 3536, and 2330 RRP patients, respectively, would have met these AS criteria. At surgery, 3%-4% had a Gleason score of 8-10, 16%-19% had positive surgical margins, 15%-18% had extracapsular tumor extension, 3%-5% had seminal vesicle invasion, and 0.4%-1% had lymph node metastasis. The 5-year progression-free survival rate ranged from 84%-89%. Metastasis occurred in 0.1%-1.2%, and 0.1%-0.9% died of PCa. On multivariate analysis, Gleason score > 6 was the strongest predictor of biochemical progression. CONCLUSIONS: A substantial proportion of men who might have been considered potential AS candidates had aggressive tumor features at RRP and/or progression. Biopsy Gleason score > 6 was the strongest predictor of adverse outcomes, highlighting the importance of limiting AS to patients with Gleason < or = 6. Overall, the accurate identification of patients with truly indolent PCa at the time of diagnosis remains challenging.

Bladder neck contracture after retropubic radical prostatectomy: incidence and risk factors from a large single-surgeon experience.

OBJECTIVE: To examine a large, single-surgeon series of patients with prostate cancer who underwent retropubic radical prostatectomy (RRP) for men with postoperative bladder neck contractures (BNCs). PATIENTS AND METHODS: From 1983 to 2007, 4132 men underwent RRP for prostate cancer by one surgeon. All patients had BN reconstruction with mucosal eversion. The bladder to membranous urethral anastomosis was made using six 2/0 chromic catgut sutures over an 18 F Foley catheter. The catheter was left in place for 10 days. Data from these men is stored in a prospective database, which was reviewed in this study for men with BNCs after RRP. Men with BNCs were compared with all other men in the series to determine risk factors for BNC development. RESULTS: Overall, BNCs developed in 110 patients (2.5%). Examining our last 500 patients there was a contemporary BNC rate of <1%. The median (range) follow-up was 44 (12-233) months. Tumour characteristics were similar in the men with BNCs and those with no BNCs, and the rates of organ-confined disease were also similar (65% vs 70%, P = 0.27). Men with BNCs had higher median preoperative prostate-specific antigen (PSA) levels (6.7 vs 5.7 mg/dL; P = 0.009) and were more likely to have PSA failure after RRP (30% vs 16%, P < 0.001). On multivariate analysis, non-nerve sparing (P = 0.003) and a surgical date before 1992 (P < 0.001) were significant predictors of BNC. Patients with BNCs had lower potency rates (49% vs 63%, P < 0.003) and continence rates (88% vs 94%, P = 0.07) at the 18-month follow-up. CONCLUSIONS: BNCs are rare, occurring in <1% in our modern series. The important surgical factors in preventing BNCs are to avoid closing the BN too tightly and attaining good apposition of the BN with the urethral stump with a watertight closure. BNCs are more common with non-nerve-sparing surgery and early in a surgeon's experience.

Outcomes of radical prostatectomy for patients with clinical stage T1a and T1b disease.

OBJECTIVE: To compare the outcomes between patients with stage T1a/b with those of patients with T1c cancer of the prostate treated with radical retropubic prostatectomy (RRP), as the appropriate management of clinical stage T1a/b prostate cancer is subject to debate; although many patients are managed expectantly, some have adverse pathological features suggesting that more active treatment might be beneficial. PATIENTS AND METHODS: From 1983 to 2003, 3478 men had RRP by one surgeon. From this group, we retrospectively identified 29 men with clinical stage T1a and 83 with clinical stage T1b disease. Using statistical analysis we compared the treatment outcomes of these patients with those of 1774 men with clinical stage T1c disease. RESULTS: Men with T1a/b disease had a significantly lower preoperative prostate-specific antigen (PSA) level, a greater proportion with organ-confined disease, and a lower mean/median prostatectomy Gleason score than those with T1c disease. Also, men with T1a/b disease were less likely to be potent before surgery, although the frequency of recovery of potency was similar among all groups. On multivariate analysis with age, year of surgery, PSA level and Gleason score, there was no statistical difference in the rates of biochemical recurrence and the 10-year overall survival rates. However, patients with T1b disease had a significantly lower cancer-specific survival. CONCLUSIONS: T1a and T1b prostate cancer can be associated with aggressive pathological features and have a similar rate of progression as clinical stage T1c disease. That notwithstanding, most patients in the study were cured with RRP and had favourable long-term functional outcomes.