History of malignancy is a predictor of prostate cancer detection: Incorporation into a pre‐biopsy nomogram

Objectives: To examine whether history of malignancy adds any significant information to the prediction of positive prostate biopsy in referred men with moderately elevated prostate‐specific antigen (PSA) and to develop a predicting nomogram that does not require extra examinations other than PSA. Methods: A total of 1767 consecutive Japanese men with PSA less than 10 ng/mL who underwent prostate biopsy were included in the study cohort. Age, digital rectal examination (DRE), PSA, body mass index, family history of prostate cancer and number of previous malignancies other than the prostate were evaluated in regard to their association with prostate cancer. A logistic regression‐based nomogram for predicting prostate cancer was developed and externally validated. Results: Of the 1767 men, 269 had a history of malignancy with a total of 312 primary sites. Univariate and multivariate analyses revealed that DRE, PSA, age, family history and number of previous malignancies are independent and significant predictors of positive biopsy result. External validation revealed that the predicting accuracy of a nomogram incorporating these five variables is significantly higher than those of PSA or PSA and DRE. Using the nomogram, 8% of unnecessary biopsies would be saved at 95% sensitivity. Conclusions: We demonstrated for the first time that history of malignancy is a potent predictor of prostate cancer in men with moderately elevated PSA even if the established risk factors are adjusted. The nomogram can be a useful tool in decision‐making of prostate biopsy. In daily practice, history of malignancy should be rigorously taken from these men before a decision is made regarding prostate biopsy.     

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.     

A prospective, randomized trial comparing the Vienna nomogram to an eight-core prostate biopsy protocol

Study Type – Diagnostic (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Several studies have shown that increasing the number of prostate biopsy cores will increase the detection rate of prostate cancer, but also risks overdiagnosing insignificant cancer, particularly in the elderly. Our study suggests that there is no significant advantage in using the Vienna nomogram to determine the number of prostate biopsies to be taken, compared to an eight‐core biopsy protocol.

OBJECTIVE

• ? To compare prostate cancer detection rates using the Vienna nomogram versus an 8‐core prostate biopsy protocol. To compare the complication rates of transrectal prostate biopsy in the two groups.

PATIENTS AND METHODS

• ? In a prospective randomized trial, men with a serum PSA ≥ 2.5 ng/ml were stratified according to serum PSA (I = PSA 2.5–10; II = PSA 10.1–30; III = PSA 30.1–50 ng/mL) and were then randomized to group A (number of cores determined according to the Vienna nomogram) or group B (8‐core prostate biopsy).
• ? Statistical analysis was performed using Student’s t‐test for parametric data, Mann‐Whitney test for nonparametric data and Fisher’s exact test for contingency tables. A two‐tailed p‐value <0.05 was accepted as statistically significant.

RESULTS

• ? In the period July 2006 to July 2009, 303 patients were randomized to group A (n = 152) or group B (n = 151). There were no significant differences in serum PSA, prostate volume, PSA density or post‐biopsy complications between the groups.
• ? The cancer detection rate was lower in group A than in group B for the whole study cohort (35.5% vs 38.4%), for those with PSA < 10 ng/ml (28.1% vs 33%) and for those with prostate volume >50 ml (22% vs 25.8%). These differences were not statistically significant (NSS).

CONCLUSION

• ? These findings suggest that there is no significant advantage in using the Vienna nomogram to determine the number of prostate biopsy cores to be taken, compared to an 8‐core biopsy protocol.

     

建立前列腺特异性抗原灰区患者重复穿刺阳性的数学模型

目的:建立预测前列腺特异性抗原(PSA)灰区患者重复穿刺阳性的数学模型。方法:选择2004~2016年158例血清PSA位于4~10ng/ml且首次穿刺病理结果为阴性的患者行重复穿刺,记录并分析患者的年龄、前列腺体积(PV)、PSA、游离PSA(fPSA)/总PSA(tPSA)、前列腺特异性抗原速率(PSAV)、前列腺特异抗原密度(PSAD)、前列腺移行带特异性抗原密度(PSAD-TZ)、超声检查(TRUS)、直肠指检(DRE)、高级别上皮内瘤变(HGPIN)、不典型小腺泡增生(ASAP)等重复活检结果的潜在预测指标。将有统计学意义的变量行二分类Logistic回归分析和建立数学模型,该模型的预测价值通过ROC曲线下面积(AUC)来评估。结果:158例前列腺重复穿刺活检患者中,前列腺癌的检出率为25.9%(41/158),单变量分析结果中统计学上有意义的指标包括Age、PV、f/tPSA、PSAD、PSAD-TZ、DRE、TRUS、Previous HGPIN、Previous ASAP(P<0.05),对以上所有变量进行二分类Logistic回归分析并建立数学模型,预测指标ASAP、HGPIN、f/tPSA、TRUS、DRE被纳入该模型。该模型AUC为89.8%,预测价值较高。结论:该数学模型可以很好的预测PSA患者重复穿刺阳性的概率,能够帮助临床医师判断哪些PSA灰区患者更适合行超声引导下前列腺重复穿刺活检术。     

建立预测中国人前列腺重复穿刺活检阳性的数学模型

目的:建立可以预测国人经直肠超声引导下重复穿刺活检阳性的数学模型。方法:170例在首次穿刺活检诊断为前列腺良性病变的患者行重复穿刺。记录并分析患者的年龄、前列腺体积、血清PSA、游离PSA(f-PSA)/总PSA(t-PSA)、PSA上升速度、PSA密度(PSAD)、直肠指检(DRE)、首次穿刺病理结果等相关因素。将变量通过逐步回归建立回归方程,在此基础上建立重复穿刺活检阳性的危险评分数学模型。该模型的预测价值通过受试者工作曲线下面积来评估。结果:170例前列腺重复穿刺活检的患者中,前列腺癌的穿刺检出率为31.8%(54/170)。建立的数学模型影响因素包括:患者的年龄、前列腺体积、PSA、f-PSA/t-PSA、PSA上升速度、PSAD、DRE、首次穿刺结果是否为上皮内瘤变。该模型预测价值较高,曲线下面积为82.4%,大于患者PSAD、前列腺体积、PSA上升速度、f-PSA/t-PSA、DRE等单因素的66.9%、72.6%、69.6%、69.3%、58.5%。结论:该数学模型是临床多因素综合分析基础上建立的,可以很好地预测前列腺重复穿刺活检阳性的概率。     

A nomogram is more accurate than a regression tree in predicting lymph node invasion in prostate cancer

OBJECTIVE

To compare the performance and discriminant properties of two instruments (a tree‐structured regression model and a logistic regression‐based nomogram), recently developed to predict lymph node invasion (LNI) at radical prostatectomy (RP), in a contemporary cohort of European patients.

PATIENTS AND METHODS

The cohort comprised 1525 consecutive men treated with RP and bilateral pelvic LN dissection (PLND) in two tertiary academic centres in Europe. Clinical stage, pretreatment prostate‐specific antigen (PSA) level and biopsy Gleason sum were used to test the ability of the regression tree and the nomogram to predict LNI. Accuracy was quantified by the area under the receiver operating characteristic curve (AUC). All analyses were repeated for each participating institution.

RESULTS

The AUC for the nomogram was 81%, vs 77% for the regression tree (P = 0.007). When data were stratified according to institution, the nomogram invariably had a higher AUC than the regression tree (Hamburg cohort: nomogram 82.1% vs regression tree 77.0%, P = 0.002; Milan cohort: 82.4% vs 75.9%, respectively; P = 0.03).

CONCLUSIONS

Nomogram‐based predictions of LNI were more accurate than those derived from a regression tree; therefore, we recommend the use of nomogram‐derived predictions.     

The presence of prostate cancer on saturation biopsy can be accurately predicted

Study Type – Diagnostic (non‐consecutive)
Level of Evidence 3b

OBJECTIVE

To improve the ability of our previously reported saturation biopsy nomogram quantifying the risk of prostate cancer, as the use of office‐based saturation biopsy has increased.

PATIENTS AND METHODS

Saturation biopsies of 540 men with one or more previously negative 6–12 core biopsies were used to develop a multivariable logistic regression model‐based nomogram, predicting the probability of prostate cancer. Candidate predictors were used in their original or stratified format, and consisted of age, total prostate‐specific antigen (PSA) level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal examination, cumulative number of previous biopsy sessions, presence of high‐grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred bootstraps re‐samples were used to adjust for overfit bias.

RESULTS

Prostate cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA, gland volume, number of previous biopsies, and presence of ASAP at any previous biopsy were independent predictors for prostate cancer (all P < 0.05). The nomogram was 77.2% accurate and had a virtually perfect correlation between predicted and observed rates of prostate cancer.

CONCLUSIONS

We improved the accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three previously included variables, i.e. age, %fPSA and prostate volume, and on three previously excluded variables, i.e. PSA, the number of previous biopsy sessions, and evidence of ASAP on previous biopsy. Our study represents the largest series of saturation biopsies to date.     

Cross‐cultural validation of a prognostic tool: example of the Kattan preoperative nomogram as a predictor of prostate cancer recurrence after radical prostatectomy

OBJECTIVE

To establish the predictive accuracy of the Kattan preoperative nomogram by comparing predictions at 5 years with actual progression in patients who had a radical prostatectomy (RP).

MATERIALS AND METHODS

We reviewed the data for 928 patients treated by RP as a first‐line treatment for localized prostate cancer, between 1994 and 2005. Recurrence was defined as one prostate‐specific antigen (PSA) level of >0.4 ng/mL. The 5‐year progression‐free probability (PFP) rate was evaluated on censured data using the Kaplan‐Meier method. Relationships between all predictor variables included in the Kattan nomogram (PSA level, biopsy Gleason scores and clinical stage) and survival were evaluated by Cox proportional‐hazards regression analysis. The discriminating ability of the nomogram was assessed by the concordance index (c‐index). Bootstrapping was used to assess confidence intervals (CIs), and then the calibration was assessed.

RESULTS

The median follow‐up was 60 months. Overall, 177 (19%) patients had a recurrence; the 5‐year PFP rate (95% CI) was 80.9 (78–83)%. Of the three variables included in the nomogram, all were associated with recurrence in a multivariate analysis (P < 0.001). The c‐index (95% CI) was only 0.664 (0.584–0.744). In general, the nomogram was not well calibrated.

CONCLUSIONS

There was a discrepancy between the predicted PFP as estimated by the Kattan nomogram and actual relapse in this group of patients. Clinicians should be aware that the nomogram is less accurate when used outside the population used to formulate the nomogram. Although more accurate tools are needed, the Kattan nomogram is still the best choice for urologists so far.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.     

Obesity and prostate cancer screening among African-American and Caucasian men

BACKGROUND: Differential prostate-specific antigen (PSA) testing practices according to obesity-related comorbid conditions may contribute to inconsistent results in studies of obesity and prostate cancer. We investigated the relationship between obesity and PSA testing, and evaluated the role of prior diagnoses and disease screening on PSA testing patterns. METHODS: Men, 40 and 79 years old and without prior prostate cancer were recruited from 25 health centers in the Southern US (n = 11,558, 85% African-American). An extensive in-person interview measured medical and other characteristics of study participants, including PSA test histories, weight, height, demographics, and disease history. Odds ratios (OR) and (95% confidence intervals) from logistic regression summarized the body mass index (BMI) and PSA test association while adjusting for socio-economic status (SES). RESULTS: BMI between 25 and 40 was significantly associated with recent PSA testing (past 12 months) (OR(25.0-29.9) = 1.23 (1.09, 1.39); OR(30-34.9) = 1.36 (1.18, 1.57); OR(35.0-39.9) = 1.44 (1.18, 1.76); OR(> or =40) = 1.15 (0.87, 1.51)). Prior severe disease diagnoses, such as heart disease, did not influence the obesity and PSA test association. However, adjustment for prior high blood pressure or high cholesterol diagnoses reduced the BMI-PSA testing associations. Physician PSA test recommendations were not associated with BMI, and results did not appreciably vary by race. CONCLUSIONS: Overweight and obese men were preferentially PSA tested within the past 12 months. BMI was not associated with physician screening recommendations. Data suggest that clinical diagnoses related to obesity increase clinical encounters that lead to preferential selection of obese men for prostate cancer diagnosis. This detection effect may bias epidemiologic investigations of obesity and prostate cancer incidence.     

Head-to-head comparison of two online nomograms for prostate biopsy outcome prediction

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? In recent years, several nomograms were developed in an effort to decrease the number of unnecessary prostate biopsies. The European SWOP‐PRI and the North American PCPT are among the most popular. However, evidence on the relative predictive accuracy is lacking. A head‐to‐head comparison on the diagnostic accuracy of two previously validated prostate cancer risk predictors on biopsy confirmed the superiority of these tools over PSA alone. Moreover, in the studied population, the European SWOP‐PRI proved to be more accurate than the North American PCPT‐CRC.

OBJECTIVE

? To compare the diagnostic accuracy of two previously validated prostate cancer risk predictors on biopsy.

PATIENTS AND METHODS

? In total, 390 consecutive patients submitted to 10‐core systematic transrectal prostate biopsy at our institution were included in this retrospective study. ? External validation of a European (European Randomized Study of Screening for Prostate Cancer derived Prostate Risk Indicator; SWOP‐PRI) and a North American (Prostate Cancer Prevention Trial Cancer Risk Calculator; PCPT‐CRC) nomogram was performed. ? The predictive accuracy of these online available nomograms was calculated based on the area under the curve derived from receiver–operator characteristic curves and then compared using the DeLong method.

RESULTS

? Both tools were confirmed to be superior to prostate‐specific antigen alone. Moreover, the SWOP‐PRI (77.9%) displays a 7.96% increase in the predictive accuracy compared to the PCPT‐CRC (69.9%) in a statistically significant fashion (P= 0.002).

CONCLUSIONS

? The results obtained in the present study confirm the utility of nomograms with respect to biopsy outcome prediction in patients with suspicion of prostate cancer. ? In the current sample of patients, the European‐based nomogram appears to be more accurate than the North American nonogram, which lacks information regarding prostate volume and prostatic ultrasonographic lesions. ? To our knowledge, this is the first study to compare the accuracy of these popular risk calculators in a specific population.     

Prostate cancer detection after a negative prostate biopsy: Lessons learnt in the Cleveland Clinic experience

Urologists are often faced with the dilemma of managing patients with a negative initial prostate biopsy in whom clinical or pathological risk for prostate cancer still exists. Such real‐life challenging scenarios might raise questions such as: Who should undergo further biopsies? What are the optimal predictors for prostate cancer on subsequent biopsies? What is the optimal biopsy protocol that should be used? When to stop the biopsy cascade? The last decade has witnessed numerous studies that have analyzed factors conferring a significant risk for cancer discovered on repeat biopsies. We and others have developed predictive models to aid decision‐making regarding pursuing further biopsies. For decades, high‐grade prostatic intraepithelial neoplasia has been considered a strong risk indicator for subsequent cancer. However, it has been recently shown that only through segmentation of this heterogeneous population does the real risk profile emerge. Biopsy templates underwent modification regarding the number and location of cores with emergence of the transrectal or brachytherapy grid transperineal saturation biopsy. However, the best biopsy protocol remains controversial. We have refined the initial biopsy template to a 14 core initial biopsy template that optimizes cancer detection, and have shown that transrectal saturation biopsy significantly improves cancer detection for repeat biopsy. Another concern is the overdiagnosis of clinically insignificant cancer on repeat biopsies, so we explored ways to limit this, and to deal with its ramifications. Through carrying out a Medline literature search, we critically evaluated pertinent articles together with emphasis of our own journey in this arena to assist in the decision‐making process for repeat biopsy population.     

A nomogram based on age,prostate-specific antigen level,prostate volume and digital rectal examination for predicting risk of prostate cancer

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) status, % free PSA and transrectal ultrasound (TRUS) findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% (223/535). The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.     

超声引导下前列腺12针系统穿刺活检增加前列腺癌检出率的研究

目的:探讨不同年龄及前列腺特异性抗原(PSA)分组对12针穿刺活检前列腺癌检出率及肿瘤特征的影响。方法:临床表现怀疑前列腺癌患者210例,按照患者的年龄分为≤59岁组、60～69岁组、70～79岁组、≥80岁组,按照PSA水平分为0～4μg/L组、4.1～10μg/L组、10.1～20μg/L组、20.1～50μg/L组、>50μg/L组,记录患者临床资料及活检结果。提出不同的穿刺方案并计算其检出率。结果:210例怀疑为前列腺癌患者,检出前列腺癌91例,总的前列腺癌检出率为43.3%,随着年龄的增长,PSA水平的提高,检出率逐渐提高。年龄的增长、PSA水平的提高与体积较大、分级较高的肿瘤密切相关。外周带穿刺与旁正中矢状尖部穿刺有较高的前列腺癌检出率。当患者年龄<60岁,PSA水平<20μg/L时,12针穿刺活检为较佳方案。结论:12针穿刺活检可以弥补6针穿刺活检的缺陷,随着患者年龄的增长,PSA水平的提高,肿瘤的体积增大、病理分级较差。传统6针穿刺法与12针相比,受患者年龄、PSA水平的影响较大。