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。     

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。     

One preoperative dose randomized against 3‐day antibiotic prophylaxis for transrectal ultrasonography‐guided prostate biopsy

OBJECTIVE

To compare the incidence of infective events between a single dose and 3‐day antibiotic prophylaxis for transrectal ultrasonography (TRUS)‐guided prostate biopsy.

PATIENTS AND METHODS

Patients were randomized to receive either one preoperative dose consisting of two ciprofloxacin 500 mg tablets 2 h before prostate biopsy, or 3 days of ciprofloxacin treatment. They had a clinical examination at study inclusion, the day of the biopsy and 3 weeks later. The day after the procedure all patients were contacted by telephone to inquire about any significant event. Biological testing and urine cultures were conducted 5 days before and then 5 and 15 days after the biopsy; a self‐administered symptom questionnaire was completed by the patient 5 days before and then at 5 and 15 days.

RESULTS

The study group included 288 men, of whom 139 were randomized to the single‐dose arm and 149 to the 3‐day arm. Six patients in each group had an asymptomatic bacteriuria with no leukocyturia. One patient in each group had documented prostatitis, with Escherichia coli identified on urine culture. The strain identified in the patient from the 3‐day group was resistant to ciprofloxacin. There was no difference between groups in symptoms at 5 and 21 days after biopsy.

CONCLUSIONS

Current TRUS‐guided prostate biopsy techniques lead to very few clinical infectious complications when accompanied by antibiotic prophylaxis. We found no argument to advocate the use of more than one dose of antibiotic prophylaxis.     

经会阴前列腺穿刺与经直肠前列腺穿刺活检在前列腺癌诊断的初探

目的 对比经会阴与经直肠前列腺穿刺活检在前列腺癌诊断中的阳性率及并发症。方法 回顾分析2017年1月到2019年12月行前列腺穿刺活检的病例,经直肠组187例,经会阴组68例。结果 经直肠组阳性穿刺率为34.7%,经会阴组阳性穿刺率为29.4%,两组无统计学差异（P>0.05）。穿刺后经直肠组和经会阴组的血尿发生率分别为40.1%、42.6%,尿潴留发生率分别为6.9%、7.3%,直肠出血发生率分别为1.1%、0%,差别无统计学意义（P>0.05）。穿刺后经直肠组和经会阴组的会阴肿胀的发生率分别为2.6%、13.2%,两组有统计学差异（P<0.05）。结论 超声引导下经直肠、经会阴前列腺穿刺活检均为前列腺癌诊断的有效方法。两者穿刺阳性率无明显差异,但并发症各有特点。     

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.

     

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.     

A nomogram for predicting upgrading in patients with low‐ and intermediate‐grade prostate cancer in the era of extended prostate sampling

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To develop a nomogram to predict the probability that the pathological Gleason sum (GS) will be higher than that indicated by the biopsy, suggesting a higher risk for the patient presumed to be at low risk, as a substantial proportion of patients with low and intermediate grade on biopsy are upgraded on interpretation of the radical prostatectomy (RP) specimens, but a similar clarification of accurate Gleason scoring is not available in patients with no surgical histology.

PATIENTS AND METHODS

The study included 1017 patients who had RP after biopsy showing GS 6 and 7 (3 + 4) from 2000 to 2007. Nomogram predictor variables included age, race, digital rectal examination, prostate‐specific antigen (PSA) level, number of cores taken, number of positive cores, maximum percentage cancer in any core, number of previous biopsies, prostate volume, clinical stage, high‐grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, inflammation and perineural invasion. We calculated the nomogram‐predicted probability in each patient. The area under the receiver operating characteristic curve was calculated as a measure of discrimination, and the calibration was assessed graphically.

RESULTS

The mean age of the patients was 60 years, the mean PSA level 6.62 ng/mL; 336 patients were upgraded (33%), 623 remained the same (61.3%) and 58 were downgraded (5.7%). A nomogram for predicting the possibility of upgrading was constructed that had a concordance index of 0.68. The nomogram was well calibrated.

CONCLUSIONS

Our nomogram for predicting upgrading provides important additional information for deciding on treatment to both the urologist and the patient with low‐ and intermediate‐grade prostate cancer. It might prove useful when the possibility of a more aggressive Gleason variant can change the management, and is especially meaningful when management options other than surgery are selected based on the inability to recognize the true pathological actual GS.     

Transperineal template‐guided mapping biopsy of the prostate

Accurate diagnosis of prostate cancer has eluded clinicians for decades. With our current understanding of prostate cancer, urologists should devise and confidently present the available treatment options – active surveillance/radical treatment/focal therapy to these patients. The diagnostic modalities used for prostate cancer have the dual problem of false negativity and overdiagnosis. Various modifications in the prostate biopsy techniques have increased the accuracy of cancer detection, but we are still far from an ideal diagnostic technique. Transperineal template‐guided mapping biopsy of the prostate is an exhaustive biopsy technique that has been improvised over the past decade, and has shown superior results to other available modalities. We have carried out a PubMed search on the available experiences on this diagnostic modality, and along with our own experiences, we present a brief review on transperineal template‐guided mapping biopsy of the prostate.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.     

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Prior studies have shown that the PCA3 Score is indicative of prostate cancer significance and may aid in selecting men with clinically insignificant prostate cancer who could be candidates for active surveillance. This analysis of data from two studies enrolling 1,009 men shows that the PCA3 Score is associated with many biopsy and pathological features of the insignificant prostate cancer. The paper also provides guidance for the use of the PAC3 Assay in clinical practice.

OBJECTIVE

• ? To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance.

PATIENTS AND METHODS

• ? Clinical data from two multi‐centre European open‐label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed.
• ? First‐catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA® PCA3 assay.
• ? Transrectal ultrasound‐guided biopsy (≥8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed.

RESULTS

• ? Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score <7 vs ≥7, with clinical stage T1c vs T2a–T2c, T3a cancers, with ≤33% vs >33% positive biopsy cores and with ‘biopsy indolent’ vs ‘biopsy significant’ prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria).
• ? In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score <7 vs ≥7, and with pathological stage T2a–T2c vs T3a–T3b cancers.

CONCLUSIONS

• ? The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance.
• ? Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP.
• ? Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment.

     

Prostate cancer diagnosis in the new millennium: strengths and weaknesses of prostate‐specific antigen and the discovery and clinical evaluation of prostate cancer gene 3 (PCA3)

The decision to take a prostate biopsy is traditionally guided by a digital rectal examination and measurement of serum total prostate‐specific antigen (tPSA). However, both techniques are subject to inherent weaknesses. The prostate cancer gene 3 (PCA3), a gene‐based marker, specific for prostate cancer, supplements the predictive power of tPSA to improve diagnosis of disease. Including this new marker in the standard of care for men at risk of prostate cancer should be considered, as it presents marked potential for better decision making for a prostate biopsy and for improving overall patient care.     

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.