prostate cancer; low risk; favourable risk
The management of localized prostate cancer is controversial, and in the absence of comparative trials to inform best practice, choices are driven by personal beliefs with wide variation in practice patterns. Men with localized disease diagnosed today often undergo treatments that will not improve overall health outcomes, and active surveillance has emerged as one approach to reducing this overtreatment of prostate cancer. The selection of appropriate candidates for active surveillance should balance the risk of harm from prostate cancer without treatment, and a patient’s personal preferences for living with a cancer and the potential side effects of curative treatments. Although limitations exist in assessing the potential for a given prostate cancer to cause harm, the most common metrics used today consider cancer stage, prostate biopsy features, and prostate-specific antigen level together with the risk of death from nonprostate causes based on age and overall state of health.
For prostate cancer patients with small, lower-grade tumors, expectant management with delayed surgical intervention (active surveillance) is a rarely used therapeutic option because the opportunity for cure may be lost. We compared outcomes of 38 patients with small, lower-grade prostate cancer in an expectant management program who underwent delayed surgical intervention at a median of 26.5 months (95% confidence interval [CI] = 17 to 32 months; range = 12.0–73.0 months) after diagnosis with 150 similar patients who underwent immediate surgical intervention at a median of 3.0 months (95% CI = 2 to 4 months; range = 1.0–9.0 months) after diagnosis. Noncurable cancer was defined as adverse pathology associated with a less than 75% chance of remaining disease-free for 10 years after surgery. Noncurable cancer was diagnosed in nine (23%) of the 38 patients in the delayed intervention cohort and in 24 (16%) of the 150 men in the immediate intervention group. After adjusting for age and prostate-specific antigen (PSA) density (i.e., PSA value divided by prostate volume) in a Mantel–Haenszel analysis, the risks of noncurable cancer associated with delayed and immediate intervention did not differ statistically significantly (relative risk = 1.08, 95% CI = 0.55 to 2.12; P = .819, two-sided Cochran–Mantel–Haenszel statistic). Age, PSA, and PSA density were all statistically significantly associated with the risk of noncurable cancer (P = .030, .013, and .008, respectively; two-sided chi-square test). Thus, delayed prostate cancer surgery for patients with small, lower-grade prostate cancers does not appear to compromise curability.
Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection.
We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age.
All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%–100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%–100%) of the cancers would still be detected by age 75 years.
These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer.
To determine whether the number of times the prostate-specific antigen (PSA) velocity (PSAV) exceeds a threshold (PSAV risk count) is predictive of high-risk prostate cancer.
The PSAV was determined in 717 men (606 without prostate cancer; 32 with high-risk prostate cancer defined as death from cancer, PSA level of 20 ng/mL or more, or a Gleason score of 8 or more; and 79 with prostate cancer who were alive or dead of another cause). Multiple PSAVs determined from three repeated measures from each subject during 10 to 20 years were used to determine the risk count by summing the number of times a subject exceeded a PSAV threshold. Cox proportional hazards regression analysis was used to evaluate the associations between the risk count and the probability of high-risk disease. The statistical tests were two-sided.
The probability of high-risk disease increased directly with the risk count. After adjusting for age, PSA level, PSAV, and date of diagnosis, the PSAV risk count was significantly associated with the development of high-risk prostate cancer (relative risk 1.41, 95% confidence interval 1.25 to 1.59 for a PSAV cutpoint 0.2 ng/mL/yr; relative risk 1.49, 95% confidence interval 1.29 to 1.71 for a PSAV cutpoint of 0.4 ng/mL/yr; P <0.001).
The PSAV risk count could be a useful method of interpreting a PSA history to help identify those men who will benefit from a diagnosis of prostate cancer at PSA levels associated with curable disease.
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.
Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time.
Materials and Methods
We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis.
On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p <0.001). Biopsy history was not associated with resistance. Of those with a resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2 resistant swabs showed resistance on the third swab. Of men with a sensitive first swab 10.6% showed resistance on the second swab and 10.6% of those with 2 sensitive swabs had resistant third swabs.
One of 4 men who present for surveillance and diagnostic trans-rectal ultrasound guided prostate biopsy have rectal flora resistant to fluooquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time.
prostatic neoplasms; biopsy; fluoroquinolones; drug resistance; bacterial; diabetes mellitus
Understanding the experiences of men leaving active surveillance programs is critical to making such programs viable for men with localized prostate cancer.
To generate hypotheses about the factors that influence patients' decisions to leave an active surveillance program.
Using data from the Johns Hopkins active surveillance cohort, bivariate analyses and multinomial regression models examined characteristics of men who self-elected to leave, those who stayed in the program, and those who left because of disease reclassification. We interviewed patients who self-elected to leave.
Of 1,159 men in active surveillance, 9 % self-elected to leave. In interviews with a sample of 14 men who self-elected to leave, uncertainty involved in active surveillance participation, existence of personal criteria— distinct from providers' clinical criteria—and fear of cancer were important factors in decisions to leave.
Men leaving active surveillance were motivated by a number of factors, including patient-defined criteria, which might differ from clinical recommendations. To ensure active surveillance participation, it may be important to address cancer-related anxiety and personal criteria underlying patient decisions.
We assessed whether the Gleason grade changes in men followed expectantly with nonpalpable prostate cancer diagnosed on needle biopsy (stage T1c).
Materials and Methods
We studied 241 men with stage T1c prostate cancer who were treated expectantly with repeat yearly needle biopsy sampling to assess for cancer progression. Following the initial cancer diagnosis all men had at least 1 other biopsy demonstrating cancer.
Median patient age was 66 years. The number of biopsies showing cancer over time was 2 in 119 (49.4%), 3 in 74 (30.7%), 4 in 33 (13.7%) and 5 or greater in 15 (6.2%). The average followup for those without progression was 32.3 months. Of 241 cases 45 (18.7%) showed a significant change in grade from Gleason score 6 or less to Gleason score 7 or greater (Gleason score 7 in 41 cases, Gleason score 8 in 4 cases). Of 45 (53.5%) cases 24 that showed progression did so within 24 months of diagnosis.
Within the first 3 years after diagnosis of Gleason score 6 prostate cancer, there is a relatively low risk of grade progression. Within the first 3 years, our data suggest that in most cases tumor grade did not evolve but rather that the higher grade component was not initially sampled since most grade changes occurred relatively soon after biopsy. Grade progression does appear to occur in some men with long-term followup who had multiple biopsies showing Gleason score 6 followed by higher grade cancer.
prostatic neoplasms; disease progression
Obesity may be associated with lower prostate-specific antigen (PSA) through hemodilution. We examined the relationship between body mass index (BMI) and PSA by age in men without prostate cancer from a longitudinal aging study to determine whether PSA needs to be adjusted for BMI.
Materials and Methods
The study population included 994 men (4937 observations) without prostate cancer in the Baltimore Longitudinal Study of Aging. Mixed effects models were used to examine the relationship between PSA and BMI (kg/m2) by age. Separate models were explored in men with prostate cancer censored at diagnosis, for percent body fat measurements, for weight changes with time, and adjusting for initial prostate size in 483 men (2523 observations) with pelvic MRI measurements.
In men without prostate cancer, BMI was not significantly associated with PSA after adjusting for age (p=0.06). A 10 point BMI increase was associated with a PSA difference of −0.03 ng/ml (95% CI, −0.40–0.49). Results were similar when men with prostate cancer were included, when percent body fat was substituted for BMI, and after adjusting for prostate volume. Longitudinal weight changes also had no significant association with PSA.
Consistent with prior studies, we found an inverse relationship between obesity and serum PSA levels. However, the magnitude of the difference was small. Thus, adjusting PSA for BMI does not appear warranted.
PSA; prostate cancer; BMI; obesity; hemodilution
To evaluate the impact of an extended pelvic lymph node dissection (EPLND) on the oncologic outcomes of men with lymph node positive prostate cancer.
Between 1992 and 2003, two surgeons at one hospital performed 1,986 and 2,279 open radical prostatectomies. The first surgeon routinely performed a limited pelvic lymph node dissection (LPLND) while the second performed an EPLND. Men with positive lymph nodes (LNs) from each cohort were compared for differences in oncologic outcomes.
In total, 94 (2.2%) men were found to have positive LNs, 21 (22.3%) from a LPLND and 73 (77.7%) an EPLND. On average, LPLND and EPLND yielded 11.4 and 14.6 nodes, respectively (p = 0.022). Between groups, there was no difference in the number of positive LNs (1.4 vs. 1.8, p = 0.223) or the proportion of patients with <15% positive nodes (57.1% vs. 69.9%, p = 0.300). At median follow-up of 10.5 years, EPLND patients had superior oncologic outcomes compared to the LPLND group: 5-year biochemical recurrence-free survival of 30.1% vs. 7.1% (p = 0.018); 10-year metastasis-free survival of 62.2% vs. 22.2% (p = 0.035); and 10-year cancer-specific survival of 83.6% vs. 52.6% (p = 0.199). This analysis demonstrated an augmented improvement in biochemical recurrence-free survival in men with <15% positive nodes.
In addition to affording valuable staging information, an EPLND may confer a therapeutic benefit to patients found to have positive lymph nodes at the time of radical prostatectomy.
lymphadanectomy; pelvic lymph node dissection; prostate cancer; radical prostatectomy
Active surveillance (AS) is a treatment option for men with very low–risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low–risk PCa, we evaluated oncologic outcomes of AA men with very low–risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP).
Patients and Methods
We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low–risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features.
AA men with very low–risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03).
AA men with very low–risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low–risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.
The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.
Materials and Methods
A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; >70).
With the exception of prostate-specific antigen (PSA)-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and over treatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.
The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence. The entire guideline is available at www.AUAnet.org/education/guidelines/prostate-cancer-detection.cfm
prostate cancer; prostate specific antigen; screening; early detection
We recently reported an increasing risk over time of hospitalization among Medicare participants after undergoing an initial prostate biopsy. Less is known about the relative risks of repeat prostate biopsies, which are frequently performed in prostate cancer screening and in active surveillance programs. We determined whether repeat biopsies are associated with an increased risk of hospitalization compared to the initial biopsy.
Materials and Methods
Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1991 to 2007 we identified 13,883 men who underwent a single prostate biopsy and 3,640 who had multiple biopsies. The 30-day hospitalization rates were compared between these groups, and with a randomly selected control population of 134,977. ICD-9 codes were then used to examine the frequency of serious infectious and noninfectious urological complications as the primary diagnosis for hospital admissions.
Initial and repeat biopsies were associated with a significantly increased risk of hospitalization within a 30-day period compared to randomly selected controls (p <0.0001). However, the repeat biopsy session was not associated with a greater risk of infectious (OR 0.81, 95% 0.49–1.32, p = 0.39) or serious noninfectious urological complications (OR 0.94, 95% CI 0.54–1.62, p = 0.82) compared to the initial biopsy.
Each biopsy was associated with a significant risk of complications compared to randomly selected controls. However, the repeat biopsy procedure itself was not associated with a greater risk of serious complications requiring hospital admission compared to the initial biopsy.
prostate; biopsy; infection; hospitalization; patient admission
Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences.
Materials and Methods
Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade.
Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm3 (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm3, p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001).
Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance.
prostate; prostatic neoplasms; African Americans; risk; neoplasm grading
An optimal prostate biopsy in clinical practice is based on a balance between adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value [NPV]), limited detection of clinically insignificant cancers, and good concordance with whole-gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling, and processing for pathologic evaluation. To date, there is no consensus in this regard. The purpose of this review is 3-fold: 1. To define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2. To define the optimal method of labeling prostate biopsy cores for pathologic processing that will provide relevant and necessary clinical information for all potential clinical scenarios, and 3. To determine the maximal number of prostate biopsy cores allowable within a specimen jar that would not preclude accurate histologic evaluation of the tissue.
Materials and Methods
A bibliographic search covering the period up to July, 2012 was conducted using PubMed®. This search yielded approximately 550 articles. Articles were reviewed and categorized based on which of the three objectives of this review was addressed. Data was extracted, analyzed, and summarized. Recommendations based on this literature review and our clinical experience is provided.
The use of 10–12-core extended-sampling protocols increases cancer detection rates (CDRs) compared to traditional sextant sampling methods and reduces the likelihood that patients will require a repeat biopsy by increasing NPV, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12 cores, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases CDR, reduces the need for repeat biopsies, and predicts pathological features on prostatectomy while transition-zone biopsies do not. There is little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for both predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (>2) appears to compromise pathologic evaluation, which can reduce CDR and increase the likelihood of equivocal diagnoses.
A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoidance of a repeat biopsy, and adequate information for both identifying men who need therapy and planning that therapy while minimizing the detection of occult, indolent prostate cancers. This literature review does not provide compelling evidence that individual site-specific labeling of cores benefits clinical decision-making regarding the management of prostate cancer. Based upon the available literature, we recommend packaging no more than two cores in each jar to avoid reduction of CDR through inadequate tissue sampling.
The purpose of this article is to review the multiparametric magnetic resonance imaging (mMRI) of the prostate and MR-guided prostate biopsy, and their role in the evaluation and management of men with low-risk prostate cancer.
We performed a literature review based on the MEDLINE database search for publications on the role of mMRI (a) in detection and localization of prostate cancer, prediction of tumor aggressiveness and progression and (b) in guiding targeted prostate biopsy.
The mMRI, particularly diffusion-weighted imaging with T2-weighted imaging, is a useful tool for tumor localization in low-risk prostate cancer as it can detect lesions that are more likely missed on extended biopsy schemes and can identify clinically significant disease requiring definitive treatment. The MR-guided biopsy of the most suspicious lesions enables more accurate and safer approach to guide enrollment into the active surveillance program. However, the MR-guided biopsy is complex. The fusion of MRI data with transrectal ultrasound for the purpose of biopsy provides a more feasible technique with documented accurate sampling.
Although the mMRI is not routinely used for risk stratification and prognostic assessment in prostate cancer, it can provide valuable information to guide management of men with low-risk disease. Incorporation of mMRI into the workup and monitoring of patients with low-risk prostate cancer can help discriminate clinically significant disease from indolent disease. Targeted biopsy of MR-suspicious lesions enables accurate sampling of potentially aggressive tumors that may affect outcomes.
Prostate cancer; Multiparametric MRI; Active surveillance; Biopsy
To investigate the association between serum prostate-specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy (‘biopsy reclassification’) in men with low PSA density (PSAD).
To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification.
Patients and Methods
We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men).
We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS.
We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer.
The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8–17.2%) when compared with ≥ 6 to <8 ng/mL (8.4, 95% CI 5.7–12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4–26.1%).
The adjusted predicted IRs of reclassification showed a similar non-linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL.
Risk for biopsy reclassification increased non-linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision-making for AS. However, longer follow-up times are needed to warrant final conclusions.
active surveillance; PSA; patient selection
We assessed oncologic outcomes at surgery in men with low risk and very low risk prostate cancer who were candidates for active surveillance.
Materials and Methods
In a prospectively collected institutional database, we identified 7,486 subjects eligible for active surveillance who underwent radical retropubic prostatectomy. Candidates were designated as being at low risk (stage T1c/T2a, prostate specific antigen 10 ng/ml or less, and Gleason score 6 or less) or very low risk (stage T1c, prostate specific antigen density 0.15 or less, Gleason score 6 or less, 2 or fewer positive biopsy cores, 50% or less cancer involvement per core) based on preoperative data. Adverse findings were Gleason score upgrade (score 7 or greater) and nonorgan confined cancer on surgical pathology. The relative risk of adverse findings in men at low risk with very low risk disease was evaluated in a multivariate model using Poisson regression.
A total of 7,333 subjects met the criteria for low risk disease and 153 had very low risk disease. The proportion of subjects at low risk found to have Gleason score upgrade or nonorgan confined cancer on final pathology was 21.8% and 23.1%, respectively. Corresponding values in those at very low risk were 13.1% and 8.5%, respectively. After adjusting for age, race, year of surgery, body mass index, and prostate specific antigen at diagnosis, the relative risk of Gleason score upgrade in men with low risk vs very low risk disease was 1.89 (95% CI 1.21–2.95). The relative risk of nonorgan confined cancer was 2.06 (95% CI 1.19–3.57).
Men with very low risk prostate cancer were at significantly lower risk for adverse findings at surgery compared to those with low risk disease. These data support the stratification of low risk cancer when selecting and counseling men who may be appropriate for active surveillance.
prostate; prostatic neoplasms; risk; disease progression; treatment outcome
To assess the performance of multiparametric magnetic resonance imaging (MRI) in identifying pathological-index (path-index) lesions, defined as cancer present in the same prostate sextant in two separate surveillance biopsies, in men followed within an active surveillance (AS) programme for low-risk prostate cancer (CaP) with extended follow-up.
Materials and Methods
A total of 50 men, representing >215 person-years of follow-up in an AS programme, who were referred for prostate MRI were randomly chosen to have their images reviewed by a radiologist with expertise in prostate MRI, who was blinded to biopsy results.
Index lesions on MRI were defined as a single suspicious lesion ≥10 mm or >2 lesions in a given prostate sextant. Lesions on MRI were considered suspicious if ≥2 abnormal parameters co-registered anatomically. Path-index lesions were defined as cancer present in a given prostate sextant on two separate biopsy sessions.
Sensitivity and specificity were calculated to test the performance of MRI for identifying path-index lesions.
Clinical and pathological features were compared between men with and without a MRI-index lesion.
A total of 31 path-index and 13 MRI-index lesions were detected in 22 and 10 patients, respectively.
Multiparametric MRI demonstrated excellent specificity and negative predictive value (0.974 and 0.897, respectively) for the detection of path-index lesions. Sensitivity (0.19) and positive predictive value (0.46) were considerably lower.
Patients with an index lesion on MRI were younger and less likely to have met the ‘Epstein’ criteria for very low-risk CaP.
Compared with men without an MRI lesion, a significant increase in biopsy reclassification was noted for men with a MRI lesion (40 vs 12.5%, P = 0.04).
A non-suspicious MRI was highly correlated with a lack of path-index lesions in an AS population.
Multiparametric MRI may be useful in both the selection and monitoring of patients undergoing AS.
prostate cancer; surveillance; magnetic resonance imaging; sensitivity and specificity
Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the utility of this marker in following prostate cancer patients on active surveillance. Thus, our objective was to examine the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program.
Materials and Methods
In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score ≥7, or >2 positive biopsy cores, or >50% involvement of any core with cancer). We also examined the association of biopsy results with total PSA, %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi=([-2]proPSA/fPSA) x (tPSA)½].
While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the above criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score≥7). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high-grade cancer.
In men on active surveillance, measures based on [-2]proPSA such as phi, appear to provide improved prediction of biopsy reclassification during follow-up. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance.
proPSA; PSA; prostate cancer; biopsy; active surveillance
We assessed the effect of age, health status and patient preferences on outcomes of surgery vs active surveillance for low risk prostate cancer.
Materials and Methods
We used Monte Carlo simulation of Markov models of the life courses of 200,000 men diagnosed with low risk prostate cancer and treated with surveillance or radical prostatectomy to calculate quality adjusted life expectancy, life expectancy, prostate cancer specific mortality and years of treatment side effects, with model parameters derived from the literature. We simulated outcomes for men 50 to 75 years old with poor, average or excellent health status (50%, 100% and 150% of average life expectancy, respectively). Sensitivity of outcomes to uncertainties in model parameters was tested.
For 65-year-old men in average health, surgery resulted in 0.3 additional years of life expectancy, 1.6 additional years of impotence or incontinence and a 4.9% decrease in prostate cancer specific mortality compared to surveillance, for a net difference of 0.05 fewer quality adjusted life years. Increased age and poorer baseline health status favored surveillance. With greater than 95% probability, surveillance resulted in net benefits compared to surgery for age older than 74, 67 and 54 years for men in excellent, average and poor health, respectively. Patient preferences toward life under surveillance, biochemical recurrence of disease, treatment side effects and future discount rate affected optimal management choice.
Older men and men in poor health are likely to have better quality adjusted life expectancy with active surveillance. However, specific individual preferences impact optimal choices and should be a primary consideration in shared decision making.
prostatic neoplasms; quality-adjusted life years; prostatectomy; watchful waiting; decision support techniques
Transrectal ultrasound guided prostate biopsy results rely on physician ability to target the gland according to the biopsy schema. However, to our knowledge it is unknown how accurately the freehand, transrectal ultrasound guided biopsy cores are placed in the prostate and how the geometric distribution of biopsy cores may affect the prostate cancer detection rate.
Materials and Methods
To determine the geometric distribution of cores, we developed a biopsy simulation system with pelvic mock-ups and an optical tracking system. Mock-ups were biopsied in a freehand manner by 5 urologists and by our transrectal ultrasound robot, which can support and move the transrectal ultrasound probe. We compared 1) targeting errors, 2) the accuracy and precision of repeat biopsies, and 3) the estimated significant prostate cancer (0.5 cm3 or greater) detection rate using a probability based model.
Urologists biopsied cores in clustered patterns and under sampled a significant portion of the prostate. The robot closely followed the predefined biopsy schema. The mean targeting error of the urologists and the robot was 9.0 and 1.0 mm, respectively. Robotic assistance significantly decreased repeat biopsy errors with improved accuracy and precision. The mean significant prostate cancer detection rate of the urologists and the robot was 36% and 43%, respectively (p <0.0001).
Systematic biopsy with freehand transrectal ultrasound guidance does not closely follow the sextant schema and may result in suboptimal sampling and cancer detection. Repeat freehand biopsy of the same target is challenging. Robotic assistance with optimized biopsy schemas can potentially improve targeting, precision and accuracy. A clinical trial is needed to confirm the additional benefits of robotic assistance.
prostate; prostatic neoplasms; biopsy; ultrasonography; robotics
Clinical guidelines recommend against routine prostate specific antigen (PSA) screening in older men and those with lower life expectancies. We examined providers’ decision-making regarding discontinuing PSA screening.
We administered a survey of primary providers from a large, university-affiliated primary care practice. Providers were asked about their current screening practices, factors that influence their decision to discontinue screening, and barriers to discontinuing screening. Bivariate and multivariable logistic regression analyses were used to examine whether taking age and/or life expectancy into account and barriers to discontinuing were associated with clinician characteristics and practice styles.
88.7% of providers participated in the survey (125 out of 141). Over half (59.3%) took both age and life expectancy into account whereas 12.2% did not consider either in their decisions to discontinue PSA screening. Providers varied with the age they typically stop screening and majority (66.4%) report difficulty in assessing life expectancy. Taking patient age and life expectancy into account was not associated with provider characteristics or practice styles. The most frequently cited barriers to discontinuing PSA screening were patient expectation (74.4%) and time constraints (66.4%). Black providers were significantly less likely than non-black providers to endorse barriers related to time constraints and clinical uncertainty, though these results are limited by the small sample size of black providers.
Though age and life expectancy often figure prominently in decisions to employ screening, providers face multiple barriers to discontinue PSA routine screening,