This retrospective study compares dynamic contrast-enhanced (DCE) MRI with the serial prostate-specific antigen (PSA) measurement for detection of residual disease following whole-gland high-intensity focused ultrasound (HIFU) therapy of prostate cancer.
Patients in whom post-HIFU DCE-MRI was followed within 3 months by ultrasound-guided transrectal biopsy were selected from a local database. 26 patients met the study inclusion criteria. Serial PSA levels following HIFU and post-HIFU follow-up MRI were retrieved for each patient. Three radiologists unaware of other investigative results independently assessed post-HIFU MRI studies for the presence of cancer, scoring on a four-point scale (1, no disease; 2, probably no disease; 3, probably residual disease; and 4, residual disease). Sensitivity, specificity and receiver operating characteristic (ROC) analysis were performed for each reader, post-HIFU PSA nadir and pre-biopsy PSA level thresholds of >0.2 and >0.5 ng ml−1.
The sensitivity of DCE-MRI for detection of residual disease for the three readers ranged between 73% and 87%, and the specificity between 73% and 82%. There was good agreement between readers (κ=0.69–0.77). The sensitivity and specificity of PSA thresholds was 60–87% and 73–100%, respectively. The area under the ROC curve was greatest for pre-biopsy PSA (0.95).
DCE-MRI performed following whole-gland HIFU has similar sensitivity and specificity and ROC performance to serial PSA measurements for detection of residual or recurrent disease.
There are different treatment options for localized prostate cancer. The success of high-intensity focused ultrasound (HIFU) is based largely on biochemical prostate specific antigen (PSA) results.
To evaluate the impact of using a low PSA threshold to perform prostate biopsies after HIFU in order to more accurately gauge treatment success.
Settings and Design:
Eleven patients underwent HIFU at Sydney Adventist Hospital in Sydney, 10 as primary and 1 as salvage therapy [post external beam radiation therapy (EBRT)]. The median age was 67 years (49–77 years). This was a prospective case series.
Materials and Methods:
Between 2006 and 2008, the Sonoblate device was used. Prostate biopsies were 12-core biopsies performed under local anesthesia, if PSA was ≥0.5 ng/mL or after two consecutive rises in PSA. The statistical analysis involved prospective data collection of results to calculate median and ranges.
The median PSA at diagnosis was 6.7 ng/mL (5.7–10.8 ng/mL). The median follow-up was 16 months (7–26 months). Nine men (82%) had post-HIFU biopsy. The median time to post-HIFU biopsy was 11.6 months (5–20 months), and all nine men had biopsy-proven residual disease.
A low threshold to re-biopsy post-HIFU reveals a high local failure rate of 82%. Oncological efficacy is questioned, and using high threshold to biopsy may therefore be overestimating the effectiveness of HIFU as a primary treatment for localized prostate cancer.
High-intensity focused ultrasound; prostate biopsy; prostate cancer
Focal therapy offers the possibility of cancer control, without the side effect profile of radical therapies. Early single centre prospective development studies using high intensity focused ultrasound (HIFU) have demonstrated encouraging genitourinary functional preservation and short-term cancer control. Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery. We describe the study design of an investigator-led UK multi-centre, single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer.
One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer (PSA < 15, Gleason ≤ 7, ≤ T2cN0M0) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping (TPM) biopsies. Unilateral dominant tumours, the so-called index lesion, will be eligible for treatment provided the contra-lateral side is free of ‘clinically significant’ disease (as defined by Gleason ≥ 7 or maximum cancer core length ≥ 4 mm). Patients will receive focal therapy using HIFU (Sonablate 500®). Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months.
Primary outcome is the absence of clinically significant disease based on 36-month post-treatment TPM biopsies. Secondary outcomes address a) genitourinary function using validated patient questionnaires (IPSS, IPSS-QoL, IIEF-15, EPIC-Urinary, EPIC-Bowel, FACT-P, EQ-5D), b) the predictive validity of imaging, and c) risk factors for treatment failure.
INDEX will be the first multi-centre, medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy.
Focal therapy; High-intensity focused ultrasound; Multi-centre; Prospective study; IDEAL guidelines
Prostate cancer is the most common tumor in men. The most commonly used diagnostic and tumor recurrence marker is Prostate Specific Antigen (PSA). After surgical removal or radiation treatment, PSA levels drop (PSA nadir) and subsequent elevated or increased PSA levels are indicative of recurrent disease (PSA recurrence). For clinical follow-up and local care PSA nadir and recurrence is often hand calculated for patients, which can result in the application of heterogeneous criteria. For large datasets of prostate cancer patients used in clinical studies PSA measurements are used as surrogate measures of disease progression. In these datasets a method to measure PSA recurrence is needed for the subsequent analysis of outcomes data and as such need to be applied in a uniform and reproducible manner. This method needs to be simple and reproducible, and based on known aspects of PSA biology.
We have created a simple Perl-based algorithm for the calculation of post-treatment PSA outcomes results based on the initial PSA and multiple PSA values obtained after treatment. The algorithm tracks the post-surgical PSA nadir and if present, subsequent PSA recurrence. Times to PSA recurrence or recurrence free intervals are supplied in months.
Use of the algorithm is demonstrated with a sample dataset from prostate cancer patients. The results are compared with hand-annotated PSA recurrence analysis. The strengths and limitations are discussed.
The use of this simple PSA algorithm allows for the standardized analysis of PSA recurrence in large datasets of patients who have undergone treatment for prostate cancer. The script is freely available, and easily modifiable for desired user parameters and improvements.
There are no Indian data of high-intensity focused ultrasound (HIFU). Being an alternative, still experimental modality, reporting short-term safety outcome is paramount.
This study was aimed at to assess the safety and short-term outcome in patients with prostate cancer treated by HIFU.
Settings and Design:
A retrospective study of case records of 30 patients undergoing HIFU between January 2008 to September 2010 was designed and conducted.
Materials and Methods:
The procedural safety was analyzed at 3 months. Follow-up consisted of 3 monthly prostate-specific antigen (PSA) levels and transrectal biopsy if indicated. All the patients had a minimum follow-up of 6 months.
A mean prostate volume of 26.9 ± 8.5 cm3 was treated in a mean time of 115 ± 37.4 min. There was no intraoperative complication. The postoperative pain visual analogue score at day 0 was 2.1 ± 1.9 and at day 1 was 0.4 ± 0.8 on a scale of 1-10. Mean duration of perurethral catheter removal was 3.9 days. The complications after treatment were: LUTS in seven patients, stress incontinence in two, stricture in two, and symptomatic urinary tract infection in five. Average follow-up duration was 10.4 months (range, 6-20 months). Mean time to obtain PSA nadir was 6 ± 3 months with a median PSA nadir value of 0.3 ng/ml. Two patients had positive prostatic biopsy in the localized (high risk) group.
HIFU was safe in carcinoma prostate patients. The short-term results were efficacious in localized disease. The low complication rates and favorable functional outcome support the planning of further larger studies.
Carcinoma prostate; high-intensity focused ultrasound; minimally invasive treatment; quality of life
To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost.
Materials and methods
Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml.
Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6.
We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.
The purpose of this study was to evaluate the relationship between the kinetics of PSA decline after androgen deprivation therapy (ADT) initiation and overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (HSPC).
We identified a cohort of metastatic HSPC patients treated with androgen deprivation therapy (ADT) using our institutional database. Patients were included if they had at least 2 serum PSA determinations before nadir PSA and at least one serum PSA value available within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation, nadir PSA, time to PSA nadir (TTN) and PSA decline (PSAD) in relation to OS were analyzed.
179 patients were identified, with a median follow-up after ADT initiation of 4.0 years. Median OS after ADT initiation was 7.0 years. Median PSA at ADT initiation and PSA nadir were 47 and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months, a PSAD >52 ng/mL/year, PSA nadir ≥ 0.2 ng/mL, a PSA≥47.2 ng/mL at ADT initiation and Gleason score >7, were associated with a shorter OS. On multivariate analysis, TTN<6 months, Gleason score >7 and a PSA nadir ≥ 0.2 ng/mL independently predicted a shorter OS.
To our knowledge, this is the first report to show that a faster time to reach a PSA nadir post-ADT initiation is associated with shorter survival duration in men with metastatic HSPC. These results need confirmation, but may indicate that a rapid initial response to ADT indicates more aggressive disease.
Prostate cancer; androgen deprivation therapy; hormone-sensitive metastatic prostate cancer; PSA kinetics; Time to PSA nadir
To investigate the relationship between prostate volume and the increased risk for being diagnosed with prostate cancer (PCa) in men with slowly increasing prostate specific antigen (PSA).
Materials and Methods
A cohort of 1035 men who visited our hospital's health promotion center and were checked for serum PSA levels more than two times between January 2001 and November 2011 were included. Among them, 116 patients had a change in PSA levels from less than 4 ng/mL to more than 4 ng/mL and underwent transrectal ultrasound guided prostate biopsy. Median age was 55.9 years and 26 (22.4%) had PCa. We compared the initial PSA level, the last PSA level, age, prostate volume, PSA density (PSAD), PSA velocity, and follow-up period between men with and without PCa. The mean follow-up period was 83.7 months.
Significant predictive factors for the detection of prostate cancer identified by univariate analysis were prostate volume, follow-up period and PSAD. In the multivariate analysis, prostate volume (p<0.001, odds ratio: 0.890) was the most significant factor for the detection of prostate cancer. In the receiver operator characteristic curve of prostate volume, area under curve was 0.724. At the cut-off value of 28.8 mL for prostate volume, the sensitivity and specificity were 61.1% and 73.1% respectively.
In men with PSA values more than 4 ng/mL during the follow-up period, a small prostate volume was the most important factor in early detection of prostate cancer.
Prostatic neoplasms; prostate-specific antigen; early diagnosis; organ size
The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF).
Methods and Materials
Between July 1992 and March 2004, 163 men with a Gleason score of 8–10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. ≥12 months).
Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4–96). The 5-year BF rate stratified by a PSA-SR of ≤0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), ≤0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), ≤0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and ≤1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis.
The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.
Prostate cancer; Radiotherapy; Androgen deprivation therapy; Prostate-specific antigen; Biochemical failure
Purpose of review
Prostate cancer is the most common noncutaneous malignancy in US men, and is most frequently diagnosed through prostate-specific antigen (PSA)-based screening. Nevertheless, PSA testing has become increasingly controversial. In this review, we will present the evidence supporting the role of PSA in prostate cancer screening.
Numerous studies have shown that the risk of current and future prostate cancer is directly related to the serum PSA level. Moreover, increasing PSA levels predict a greater risk of adverse pathologic features and worse disease-specific survival. Substantial epidemiologic evidence has suggested a reduction in advanced disease and improvements in prostate cancer survival rates since the introduction of PSA-based screening. Recently, evidence from a randomized trial further validated that PSA testing reduces both metastatic disease and prostate cancer-specific mortality.
PSA is a valid marker for prostate cancer and its aggressiveness. Level 1 evidence is now available that PSA-based screening reduces both the rate of metastatic disease and prostate cancer-specific mortality.
prostate cancer; screening; prostate-specific antigen; detection
Capsaicin is the main pungent component of chili peppers. This is the first case, to our knowledge, that describes prostate-specific antigen (PSA) stabilization in a patient with prostate cancer, who had biochemical failure after radiation therapy. A 66-year-old male underwent radiotherapy treatment for a T2b, Gleason 7 (3+4) adenocarcinoma of the prostate, with a PSA level of 13.3 ng/mL in April 2001. He had 3-dimensional conformal radiotherapy of 46 Gy in 23 fractions to the prostate and pelvis, and a prostate boost of 30 Gy in 15 fractions. Radiotherapy was completed in May 2001 and PSA nadired in January 2002 (0.57). Due to the continued PSA rise, the patient was started on bicalutamide (50 mg orally, daily) and leuprolide acetate (1 dose of 22.5 mg intramuscularly) in July 2005 when PSA was 38.5 ng/mL. Due to poor tolerance of androgen ablation therapy, the patient discontinued treatment and started taking 2.5 mL of habaneros chili sauce, containing capsaicin, 1 to 2 times a week in April 2006. Prostate-specific antigen doubling time (PSAdt) increased from 4 weeks before capsaicin to 7.3 months by October 2006. From October 2006 until November 2007, the patient remained on capsaicin (2.5 to 15 mL daily) and his PSA was stable (between 11 to 14 ng/mL). By January 2008, his PSA rose to 22.3 and he has maintained a PSAdt between 4 and 5 months, where it presently remains. Due to the patient’s continued PSA rise, he was restarted on bicalutamide (12.5 mg daily). Apart from PSA relapse, the patient remains free of signs or symptoms of recurrence.
Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease.
PSA velocity was determined in 980 men (856 without prostate cancer, 104 with prostate cancer who were alive or died of another cause, and 20 who died of prostate cancer) who were participants in the Baltimore Longitudinal Study of Aging for up to 39 years. The relative risks (RRs) of prostate cancer death and prostate cancer–specific survival stratified by PSA velocity were evaluated in the three groups of men by Cox regression and Kaplan–Meier analyses. Statistical tests were two-sided.
PSA velocity measured 10–15 years before diagnosis (when most men had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later; survival was 92% (95% confidence interval [CI] = 84% to 96%) among men with PSA velocity of 0.35 ng/mL per year or less and 54% (95% CI = 15% to 82%) among men with PSA velocity above 0.35 ng/mL per year (P<.001). Furthermore, men with PSA velocity above 0.35 ng/mL per year had a higher relative risk of prostate cancer death than men with PSA velocity of 0.35 ng/mL per year or less (RR = 4.7, 95% CI = 1.3 to 16.5; P = .02); the rates per 100 000 person-years were 1240 for men with a PSA velocity above 0.35 ng/mL per year and 140 for men with a PSA velocity of 0.35 ng/mL per year or less.
PSA velocity may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease.
Introduction: Black men have a higher incidence of advanced stage at diagnosis and mortality from prostate cancer than do men in other racial groups. Given that androgen-deprivation therapy (ADT) is one of the mainstays of treatment for advanced prostate cancer, we investigated the development of biochemical failure, or recurrence of elevated prostate-specific antigen (PSA) levels, among different races in men receiving ADT.
Methods: Patients with prostate cancer who received ADT in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006 were eligible for inclusion in our study. Patients who had prior treatment for their cancer with surgery or radiation were excluded. Treatment failure was defined as an increase in PSA of >2 ng/mL from PSA nadir, with no subsequent decrease in PSA. We compared the biochemical failure rate in white patients to those in black, Hispanic, and Asian/other patients. The Cox proportional hazards regression model was used to estimate hazards ratios.
Results: Our study population consisted of 681 patients: 416 (61%) were white; 107 (16%) were black; 107 (16%) were Hispanic; and 51 (7%) were Asian or another race. After we controlled for all demographic variables and for variables related to prostate cancer, blacks were the only group with a lower risk of treatment failure compared with whites. The hazard ratios for treatment failure were as follows: black versus white, 0.66 (p = 0.03); Hispanic versus white, 1.00 (p = 0.8); Asian/other race versus white, 1.5 (p = 0.1). In this multivariate analysis, pretreatment PSA level and cancer stage were the only other variables associated with a higher risk of treatment failure.
Conclusion: Among patients receiving ADT as primary monotherapy for prostate cancer, blacks may have a lower rate of biochemical failure compared with whites. Although the etiology of this finding is unclear, it suggests the possibility that prostate cancer in black men may be more androgen sensitive than it is in white men.
We previously showed that prostate-specific antigen (PSA) nadir after radical prostatectomy (RP) significantly predicts biochemical recurrence (BCR). Herein, we sought to explore the effect of including PSA nadir into commonly used models on their accuracy to predict BCR after RP.
This was a retrospective analysis of 943 and 1792 subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Cancer (DPC) databases, respectively. The discrimination accuracy for BCR of seven previously published models was assessed using concordance index and compared with and without adding PSA nadir level in SEARCH. Using data from SEARCH, we developed a new nomogram incorporating PSA nadir to other known predictors (preoperative PSA, pathological Gleason score, PSA nadir level, surgical findings, prostate weight, body mass index and race) of BCR and externally validated it in the DPC.
In SEARCH, the mean concordance index across all seven nomograms was 0.687. After the inclusion of PSA nadir, the concordance index increased by nearly 7% (mean = 0.753). The concordance index of the new nomogram in SEARCH was 0.779 (bias-corrected = 0.767), which was 5% better than the next best model. In DPC, the new nomogram yielded a concordance index of 0.778.
The addition of postoperative PSA nadir to commonly used nomograms increased their accuracies by nearly 7%. Based upon this, we developed and externally validated a new nomogram, which was well calibrated and highly accurate, and is a potentially valuable tool for patients and physicians to predict BCR after RP.
disease-free survival; nomograms; prostate cancer; prostate-specific antigen; prostatectomy; validation studies
This study was conducted to evaluate the incidence of prostate cancer (PCa) in Iranian male patients with increased prostate-specific antigen (PSA), and normal or abnormal digital rectal examination (DRE) that underwent prostate biopsy.
Materials and methods:
From March 2006 to April 2009, a total of 346 consecutive males suspected of having PCa due to increased PSA levels underwent transrectal ultrasonography (TRUS)-guided sextant biopsy of the prostate. The total PSA (tPSA), demographic data, incidence of PCa, benign prostate hyperplasia (BPH), and prostatitis were assessed.
The patients were divided into two groups according to their PSA values (group A serum tPSA level, 4–10 ng/mL; group B serum tPSA level, 10.1–20.0 ng/mL). Of the 346 biopsied cases, 193 cases (56%) had PCa, 80 cases (23%) had BPH, and 73 cases (21%) had prostatitis. The mean PSA and the age of the carcinoma group were significantly higher than those of the benign group (P < 0.01). The biopsy results were grouped as PCa, BPH, and prostatitis. Incidence of PCa for group A and group B cases were 115 cases (51%), and 78 cases (65%), respectively. In the case of PCa, BPH, and prostatitis, the mean PSAs were 10.02 ng/mL, 8.76 ng/mL, and 8.41 ng/mL, respectively (P < 0.40).
TRUS-guided prostate biopsy and interpretation by a skilled team is highly recommended for early detection of PCa or its ruling-out. It seems that a PSA cutoff value of 4 ng/mL may be applied to the Iranian population. Although the chance of PCa is high in the PSA levels of 4–10 ng/mL, the combination of some data, like age and prostate volume, can decrease the rate of unnecessary prostate biopsies. We recommend prostate biopsy when PSA and/or DRE is elevated in symptomatic patients with obstructive and/or irritative lower urinary tract symptoms (LUTS) such as dysuria, frequency, or nocturia. Due to the very high incidence of PCa in the patients with PSA greater than 10 ng/mL, TRUS-guided biopsy is indicated, whatever the findings on DRE and/or LUTS, since the PCa detection rate is high.
prostate-specific antigen; benign prostate hyperplasia; BPH; prostate biopsy; prostate carcinoma; PCa; digital rectal examination; DRE; lower urinary tract symptoms; LUTS
Prostate-specific antigen (PSA) was recently found in 30% of female breast tumours. In this study we have examined if PSA circulates in the blood of breast cancer patients and if serum PSA has any clinical application. We have compared serum PSA levels between women with and without breast cancer, between women with PSA-positive and PSA-negative breast cancer and between women with breast cancer before and after surgical removal of the tumour. We found that for women > or = 50 years, there is no difference in serum PSA between normal or breast cancer patients. We also could not find any difference in presurgical or post-surgical serum PSA between women who have PSA-positive or PSA-negative breast cancer. We found no correlation between PSA concentrations in matched presurgical and post-surgical sera, between presurgical sera and tumour cytosols and between post-surgical sera and tumour cytosols. High-performance liquid chromatography has shown that PSA in normal male serum consists mostly of PSA bound to alpha 1-antichymotrypsin (molecular weight approximately 100,000), and PSA in breast tumours and presurgical and post-surgical serum consists mostly of free PSA (molecular weight approximately 33,000). These data suggest that female serum PSA is not associated with tumour PSA levels. We speculate that most of the circulating PSA in women originates from the normal breast. It appears that serum PSA in women does not have potential for breast cancer diagnosis or monitoring, but our previous data are consistent with the view that tumour PSA concentration is a favourable prognostic indicator in women with breast cancer.
Recent studies have identified genetic variants associated with both increased serum PSA concentrations and prostate cancer risk, raising the possibility of diagnostic bias. By correcting for the effects of these variants on PSA levels, it may be possible to create a personalized PSA cutoff to more accurately identify individuals for whom biopsy is recommended. We therefore determined how many men would continue to meet common biopsy criteria after genetic correction of their measured PSA concentrations.
MATERIALS AND METHODS
The genotypes of 4 single nucleotide polymorphisms (SNPs) previously associated with serum PSA levels (rs2736098, rs10788160, rs11067228, and rs17632542) were determined in 964 healthy Caucasian volunteers without prostate cancer. Genetic correction of the PSA was performed by dividing an individual's PSA value by his combined genetic risk. Analyses were used to compare the percentage of men that would meet commonly used biopsy thresholds (≥2.5 or ≥4.0 ng/mL) before and after genetic correction.
Genetic correction of serum PSA results was associated with a significantly decreased frequency of men meeting biopsy thresholds. Genetic correction could lead to a 15% and 20% relative reduction in the total number of biopsies using a biopsy threshold of ≥2.5 or ≥4.0 ng/mL, respectively. In addition, genetic correction could result in an 18–22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.
Our results suggest that 4 SNPs can be used to adjust a man's measured PSA concentration and potentially delay or prevent unnecessary prostate biopsies in Caucasian men.
prostate cancer; genetic variants; PSA; prostate biopsy
Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection were evaluated among 3927 U.S. men, 40–85 years of age, who participated in the 2001–2006 National Health and Nutrition Examination Surveys. Five recommended definitions of prostate cancer detection were adopted using total and free prostate specific antigen (tPSA and fPSA) laboratory measurements. Men were identified as high-risk based on alternative cut-offs, namely, tPSA>10 ng/ml, tPSA>4 ng/ml, tPSA> 2.5 ng/ml, %fPSA<25% and %fPSA<15%. %fPSA was defined as (fPSA÷tPSA)×100%. Serum levels of vitamin A (retinol, retinyl esters) and carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene) were defined as quartiles and examined as risk/protective factors for PSA biomarkers. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using binary logistic models. After adjustment for known demographic, socioeconomic and lifestyle confounders, high serum levels of retinyl esters (tPSA>10 ng/ml: Q4vs.Q1→OR=0.38, 95% CI: 0.14–1.00) and α-carotene (%fPSA<15%: Q4vs.Q1→OR=0.49, 95% CI: 0.32–0.76) were associated with a lower odds whereas high serum level of lycopene (tPSA>2.5 ng/ml: Q4vs.Q1→OR=1.49, 95% CI: 1.01–2.14) was associated with a greater odds of prostate cancer detection. Apart from the three significant associations observed, no other exposure-outcome association was significant. Monitoring specific antioxidant levels may be helpful in early detection of prostate cancer.
vitamin A; carotenoids; prostate cancer; prostate-specific antigen
In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA ⩽10, stage ⩽T2a, or Gleason grade ⩽6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r2=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r2 =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.
British Journal of Cancer (2002) 87, 726–728. doi:10.1038/sj.bjc.6600526 www.bjcancer.com
© 2002 Cancer Research UK
prostate cancer progression; insulin; growth factors
Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents.
We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center.
In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed.
Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC.
Castration refractory prostate cancer; Chemotherapy; Prostate-specific antigen
The histological changes (both macroscopic and microscopic) in the prostate following the combination of external beam radiotherapy and salvage high intensity focused ultrasound (HIFU) have not been previously described. This article describes the case of a 65-year-old male who presented with recurrent localized prostate cancer after undergoing external beam radiotherapy for low-risk prostate cancer. He was treated with salvage HIFU, and 4 weeks later presented with symptoms and signs consistent with a prostatorectal fistula. During a period of conservative management, his serum prostate-specific antigen levels started rising after having reached a nadir. A radical cystoprostatectomy and repair of fistula were performed after conservative management failed. Histological changes of dense fibrosis were noted in the region where the prostate should have been located. A literature review of the histological findings in the prostate after HIFU is discussed in this article, as well as the available evidence for the management of patients with local failure after the combination of external beam radiotherapy and salvage HIFU.
To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.
We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone.
Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce.
Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.
Prostate cancer; Brachytherapy; PSA bounce; Post-dosimetry; UD90 (%)
To investigate whether tumor aggressiveness in patients with prostate cancer has changed in Korea since the introduction of prostate-specific antigen (PSA) testing.
Materials and Methods
The data from 2,508 patients with pathologically confirmed prostate cancer who underwent radical prostatectomy at Asan Medical Center between 2000 and 2011 were reviewed. The patients were divided into four 3-year time series, and the changes between the groups in terms of serum PSA levels, pathological Gleason score (GS), and pathological stage were assessed. The change in GS over time in organ-confined disease and in patients whose PSA was below 10 ng/ml was also analyzed.
The mean PSA levels dropped significantly over the 12-year period (p<0.001). The frequency of organ-confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2% vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0% vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than 70%) of all cases had a high GS (7 or greater) at all time points. The GS distribution did not change over time in patients whose PSA levels were below 10 ng/ml or in those who had organ-confined disease.
In 2000 to 2011, the preoperative PSA, pathological stage, and pathological GS dropped. However, the majority of the prostate cancers in Korean men were poorly differentiated, even when the patients had organ-confined disease or their PSA levels were less than 10 ng/ml.
Korea; Neoplasm grading; Prostatic neoplasms
Most pretreatment risk-assessment models to predict biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer rely on total prostate-specific antigen (PSA), clinical stage, and biopsy Gleason grade. We investigated whether free PSA (fPSA) and human glandular kallikrein-2 (hK2) would enhance the predictive accuracy of this standard model. Preoperative serum samples and complete clinical data were available for 1,382 patients who underwent RP for localized prostate cancer from 1993 − 2005. A case-control design was utilized, and conditional logistic regression models were used to evaluate the association between preoperative predictors and BCR after RP. We constructed multivariable models with fPSA and hK2 as additional preoperative predictors to the base model. Predictive accuracy was assessed with the area under the ROC curve (AUC). There were 146 BCR cases; the median follow up for patients without BCR was 3.2 years. Overall, 436 controls were matched to 146 BCR cases. The AUC of the base model was 0.786 in the entire cohort; adding free PSA and hK2 to this model enhanced the AUC to 0.798 (p=0.053), an effect largely driven by free PSA. In the subgroup of men with tPSA ≤10 ng/ml (48% of cases), adding free PSA and hK2 enhanced the AUC of the base model to a similar degree (from 0.720 to 0.726, p=0.2). Free PSA is routinely measured during prostate cancer detection. We suggest that the role of fPSA in aiding preoperative prediction should be investigated in further cohorts.
free PSA; PSA; human kallikrein 2; prostate cancer; biochemical recurrence; radical prostatectomy
INTRODUCTION: We report the incidence, clinicopathologic features, and outcomes of men who presented to an inner-city hospital with serum PSA >20 ng/ml. MATERIALS AND METHODS: Five-hundred-sixty men underwent a transrectal ultrasound needle-guided biopsy of the prostate for elevated PSA >4 ng/ml with or without an abnormal digital rectal examination. RESULTS: Of the 560 men, 65 (12%) were found to have a serum PSA >20 ng/ml, and 57 (10%) were diagnosed with prostate cancer. In the group of 57 men with cancer, the positive predictive value of PSA alone was 72% for PSA levels of 20-29.99 ng/ml and 100% for PSA >30 ng/ml. Of the 57 men, 18 underwent definitive therapy, 24 underwent androgen deprivation, 8 refused treatment or were lost to follow-up, and 7 were treated on protocol. An additional seven men with cancer refused therapy or were lost to follow-up, thus giving a total of 15 (26%) men who were noncompliant to medical advice. CONCLUSIONS: Serum PSA >30 ng/ml is an almost certain predictor of the presence of prostate cancer. Aggressive prostate cancer education and screening programs are needed in our inner cities in order to detect prostate cancer at an earlier, treatable stage.