Estimation of prostate cancer risk on the basis of total and free prostate-specific antigen,prostate volume and digital rectal examination

Background and Objective: Approximately 70% of the men with an elevated serum prostate-specific antigen (PSA) identified in prostate cancer screening do not have prostate cancer. Other available diagnostic variables may be utilized to reduce the number of false positive PSA results, but few algorithms for calculation of the combined impact of multiple variables are available. The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA, and the percentage of free PSA in serum, prostate volume and digital rectal examination (DRE) findings.Methods: In a randomized, population-based prostate cancer screening trial 10 284 men aged 55–67 years were screened during 1996 and 1997 in two metropolitan areas in Finland. Results for men (n=758) with a serum PSA of 4–20 μg/l were used to establish the risk nomograms. Of these 200 (26%) had prostate cancer at biopsy.Results: Prostate cancer probability depended most strongly on the percentage of free PSA. Total PSA, prostate volume, and DRE also contributed to prostate cancer probability, whereas age and family history of prostate cancer did not. More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA (p<0.001) or PSA density (p=0.003) alone.Conclusions: Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4–20 μg/l was observed. The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4 μg/l.     

Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors

PURPOSE: Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies. MATERIALS AND METHODS: The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms. RESULTS: Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good. CONCLUSIONS: Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.     

The role of prostate-specific antigen velocity in prostate cancer early detection

Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.     

Toward an MRI-based nomogram for the prediction of transperineal prostate biopsy outcome: A physician and patient decision tool

Purpose

To develop and internally validate a nomogram using biparametric magnetic resonance imaging (B-MRI)–derived variables for the prediction of prostate cancer at transperineal sector-guided prostate biopsy (TPSB).

Biomarkers for detection of clinically significant prostate cancer: contemporary clinical data and future directions

Use of serum prostate-specific antigen (PSA) testing for early detection of prostate cancer appears to reduce cancer-specific mortality. Due to the limited specificity of PSA for clinically significant [Grade Group (GG) ≥2] cancer, however, screening carries substantial risks, including frequent unnecessary prostate biopsies and overdetection of non-aggressive cancers. To that end, serum and urine biomarkers with improved specificity for GG ≥2 cancer have been proposed for clinical use following PSA. In the current article, we present clinical validation data for five such biomarkers: PHI, 4Kscore, SelectMDx, ExoDx, and MPS. For all studies, we specify the study population (overall biopsy referral vs. pre-specified PSA ranges), previous biopsy status (biopsy-naïve vs. previous negative biopsy), and the proportion of subjects diagnosed with GG ≥2 cancer. Outcomes include test performance characteristics: sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Published data were used to compute the number of unnecessary biopsies avoided and number of GG ≥2 cancers missed if the biomarker had been used clinically to select for prostate biopsy. The evidence review is preceded by a primer on these and other clinically-relevant summary statistics.     

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis

Objectives The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients. Materials and methods This study included 115 male hemodialysis patients aged >55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged >55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged >55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C). Results There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases. Conclusions These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.     

Development, validation, and head-to-head comparison of logistic regression-based nomograms and artificial neural network models predicting prostate cancer on initial extended biopsy

OBJECTIVES: Using cohorts examined by extended biopsy, we developed and validated multivariate models predicting prostate cancer on initial biopsy and examined whether these extended biopsy-based models outperform previously established models. METHODS: Initial extended biopsy (median 22 cores) was performed in 1509 Japanese men including 1083 at Tokyo Medical and Dental University Hospital (TMDU) and 426 at Cancer Institute Hospital (CIH). Logistic regression-based nomograms 1 and artificial neural network (ANN) 1 incorporating age, digital rectal examination, and prostate-specific antigen (PSA) and free PSA, and nomogram 2 and ANN2 further incorporating transrectal ultrasound (TRUS) findings and prostate volume were constructed on the TMDU data. These and previously established models were externally validated on the CIH data set and predictive accuracy was compared directly. RESULTS: Without TRUS-derived information, nomogram 1 outperformed the ANN1. With TRUS-derived information, nomogram 2 was more accurate than ANN2. External validation revealed applicability of the Western models to Japanese population, superiority of the nomograms over ANN models, and better predictive accuracy of our extended biopsy-based nomograms than the previous 6-10-core biopsy-based models. Using nomograms 1 and 2, 16% and 19% unnecessary biopsies would be saved at 95% sensitivity. CONCLUSIONS: We developed new nomograms predicting prostate cancer on initial biopsy in men with PSA <20ng/ml. Predictive accuracy of these extended biopsy-based nomograms is better than those of previously established models based on 6-10-core biopsies. Our models might help clinicians to decide if a patient requires biopsy and to avoid unnecessary biopsies.     

Biochemical staging of prostate cancer

PSA continues to be one of the most effective and widely used cancer screening tools available. Its popularity in prostate cancer screening, however, has eroded its usefulness in the staging of this disease. As more men are screened every year on a routine basis with DRE and PSA, the average PSA at diagnosis has drifted down to well below 10 ng/mL in many centers, including ours. This trend is likely to accelerate, as a PSA cut off for prompting biopsy of the prostate of 2.5 ng/mL gains more widespread acceptance. The recent realization that, at these levels, serum PSA is more reflective of the presence of BPH than of the extent of cancer and, therefore, does not provide additional staging information, has renewed the search for new biochemical markers that are capable of predicting prostate cancer stage and prognosis. Because of the heterogeneity of this disease, it is unlikely that a single biochemical marker that is capable of accurately staging all prostate cancer patients will be found. For this reason, nomograms that are capable of integrating various parameters to predict stage and prognosis will remain indispensable. As new biochemical markers that provide independent predictive information about stage or prognosis are identified, they can be incorporated into currently available nomograms. Of the biochemical markers discussed in this article, IL-6sR and TGF-beta1 are the most promising. By incorporating them into a preoperative nomogram designed to predict PSA recurrence, we found that they improved the ability to predict biochemical recurrence by a statistically and clinically significant margin. The ability to stage prostate cancer and predict response to therapy has improved dramatically over the last 3 decades. Nevertheless, there is still a need for new biochemical markers that will improve the ability to predict an individual patient's stage and response to therapy. Incorporating these new markers into nomograms will enhance the ability to provide optimal care for each prostate cancer patient.     

Defining prostate cancer risk before prostate biopsy

Prostate cancer is the most commonly diagnosed cancer in men. At present, patients are selected for prostate biopsy on the basis of age, serum prostate specific antigen (PSA), and prostatic digital rectal examination (DRE) findings. However, due to limitations in the use of PSA and DRE, many patients undergo unnecessary prostate biopsy. A further problem arises as many patients are diagnosed and treated for indolent disease. This review of the literature highlights the strengths and weaknesses of existing methods of prebiopsy risk stratification and evaluates promising serum, urine, and radiologic prostate cancer biomarkers, which may improve risk stratification for prostate biopsy in the future.     

Low reduction of prostate volume is a significant predictor of prostate cancer at subsequent biopsy in patients with dutasteride: A retrospective study

Appropriate decision of prostate biopsy in men with 5α-reductase inhibitor (5AR inhibitor) is still unclear to avoid unnecessary biopsy. We retrospectively investigated patients with initial PSA 4.0 ng/ml or more and underwent subsequent prostate biopsy following dutasteride treatment. From September 2009 to August 2018, 399 cases of benign prostate hyperplasia (BPH) were treated with dutasteride in our department. Of the total, 36 cases with elevated pre-treatment PSA (4.0 ng/ml or more) and underwent subsequent prostate biopsy were included into this study. We evaluated PSA kinetics and changing prostate volumes (PV), and detection of prostate cancer. Overall, average PSA reduced by half at 6 months from dosing. Pre-treatment biopsy was performed in 17 of 36 cases, and all were diagnosed as having no malignancy. After treatment, prostate cancer was detected in 15 cases by subsequent biopsy. Fourteen of 15 cases were clinically significant cancer (Gleason score 7 or more). Logistic regression analysis detected a nominal association between prostate cancer detection and three variants, PSAD, PV reduction (1–Before/After PV) and abnormal MRI findings. In addition to abnormal MRI findings and pre-treatment of high PSAD, the case with low reduction of PV after treatment should consider performing prostate biopsy.     

PSA Levels and the Probability of Prostate Cancer on Biopsy

Objectives: Approaches to screening for prostate cancer have continued to be refined since the introduction of prostate-specific antigen (PSA). Since the introduction of PSA, increasing numbers of patients are presenting solely with an elevated PSA, and palpably normal prostate gland. As newer understanding emerges regarding the meaning of an isolated PSA elevation, urologists are becoming more enabled to counsel their patients and project a more accurate prediction of the likelihood of cancer on biopsy. The following will be a review of PSA in determining the presence of cancer on biopsy.Methods: PubMed and Medline literature searches as well as bibliographic reviews of published peer reviewed journals were performed to select articles regarding PSA and screening for prostate cancer. Relevant articles were reviewed and the data summarized as they pertain to interpreting PSA levels and predicting the presence of prostate cancer.Results: Widespread use of PSA for early detection has resulted in clinical stage T1c becoming the most prevalent presenting stage. For values of PSA between 4.0 and 10.0 ng/ml, there exist a 22–27% likelihood of cancer, while those above 10 ng/ml yield up to a 67% chance of cancer. It must be stressed that DRE must be combined with interpretation of PSA as up to 25% of men with prostate cancer have PSA levels within the normal range 0–4 ng/ml.Conclusions: Evaluation of PSA in the context of prostate volume (PSAD), velocity (PSAV), and age-specific reference ranges, percent-free PSA, and predictive nomograms combining values have allowed for more accurate prediction of the likelihood of prostate cancer prior to biopsy.     

Deciding whom to biopsy

Biopsy results from the Prostate Cancer Prevention Trial (PCPT) showed that prostate cancer exists at all PSA levels and that a significant number of men with “normal” PSA levels have high grade cancer. These findings and the low specificity of total PSA in discriminating cancer from benign disease have added to the debate about how best to use PSA in selecting men for prostate biopsy. Lower PSA thresholds for consideration of biopsy, particularly in younger men, are advocated by some. PSA velocity measurements may assist in the identification of men most likely to harbor cancer, and lower PSA velocity thresholds may be more appropriate in younger men. A more individualized approach using a predictive model developed from PCPT biopsy results is promoted by others. While able to incorporate risk variables other than PSA, including new markers, this risk calculator does not include PSA velocity since this variable was not found to have independent predictive value in this model. This article will present differing viewpoints on selecting men for prostate biopsy, one advocating the use of a PSA cut-off or PSA velocity measure (Dr. Catalona) and the other arguing for the routine use of established risk nomograms (Dr. Klein).     

PSA testing: an evolving relationship with prostate cancer screening

PSA testing has made prostate cancer screening a reality for men in many parts of the world, but its benefit for men's health continues to be debated. In men exposed to PSA testing, there has been a well-documented change in the presentation of prostate cancer with a shift towards earlier pathological stage, not without justifiable concern about over-diagnosis by prostate biopsy. Increasingly, men now diagnosed with early stage cancer have previous PSA exposure and are selected for biopsy based on PSA change in relation to cutoff values. Some recent observations suggest that PSA may no longer be an effective marker for early stage tumours, with PSA elevation failing to discriminate tumour-specific characteristics from benign gland enlargement. Traditionally, variation in pathological stage of clinically localised prostate cancer at diagnosis has related to clinical stage, PSA and biopsy Gleason grade, but with distinctions based upon these three assessments declining and an increasing proportion of organ-confined tumours at presentation, new methods of cancer detection and prognostic assessment are now required. Molecular technologies hold great promise in this respect, and in the future biomarker signatures are likely to overshadow total PSA for guiding early diagnosis and prognostic assessment. While arguments about prostate screening will continue, owing not least to its feasibility, future debate is likely to focus increasingly on technological advances and molecular profiling of these notoriously heterogeneous tumours.     

Prevalence of prostate specific antigen testing for prostate cancer in elderly men

PURPOSE: We investigated the prevalence and outcome of PSA testing for prostate cancer screening or diagnosis in elderly men 75 years or older at our academic medical center. MATERIALS AND METHODS: A cross-sectional study design was used to identify all men 75 years or older who underwent a PSA test through the family medicine or internal medicine service at our institution between January 1, 1998 and June 30, 2004. All patients with a suspected (PSA less than 0.1 ng/ml) or confirmed prior diagnosis of prostate cancer were excluded. The prevalence of PSA testing was then compared to that in younger age groups (45 to 54, 55 to 64 and 65 to 74 years). We then examined the frequency and nature of further evaluation and treatment performed in men following the PSA test. RESULTS: The 8,787 male patients who were 75 years or older generated a total of 82,672 visits in the 5.5-year period. Of these patients 505 (5.7%) underwent at least 1 PSA test. The prevalence of PSA testing in the younger age groups was 10.3% (1,769 of 17,175) in patients 45 to 54 years old, 14.9% (2,052 of 13,772) in those 55 to 64 years old and 11.8% (1,258 of 10,661) in those 65 to 74 years old (chi-square test p <0.001). Of these patients 98 of 343 (28.6%) with PSA between 0.1 and 4 ng/ml were referred to a urologist at our institution and 3 underwent biopsy. None had a prostate cancer diagnosis. Of the 162 patients with PSA more than 4 ng/ml 84 (51.9%) were referred to a urologist. Only 10 of the 84 patients (11.9%) who were referred to a urologist underwent prostate biopsy. Six of the 10 men (60%) were diagnosed with prostate cancer, including 1 with a Gleason 6 tumor, 1 with a Gleason 7 tumor and 4 who were found to have tumors with a Gleason score of 8 or greater. All patients received androgen deprivation therapy, except 1 who received local external beam radiation therapy. An additional patient was diagnosed by biopsy of a vertebral lesion and he received hormone therapy. At a median followup of 51 months (range 28 to 72) 4 of 7 men (57%) were alive with disease. CONCLUSIONS: PSA testing for prostate cancer screening and diagnosis appear to decrease with advancing age. A small but significant proportion of men who are 75 years or older continue to undergo PSA testing. Abnormal PSA results do not always result in further evaluation and therapy for prostate cancer in elderly men. The establishment of firm guideline recommendations regarding PSA testing and further evaluation for prostate cancer in elderly men, perhaps based on individualized geriatric assessment, may be helpful.     

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

OBJECTIVE: To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS: Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for > or = 6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION: Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer.     

Serum Pro Prostate Specific Antigen Improves Cancer Detection Compared to Free and Complexed Prostate Specific Antigen in Men With Prostate Specific Antigen 2 to 4 Ng/Ml

PurposePro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml.Materials and MethodsResearch use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221).ResultsIn PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001).ConclusionsThe %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.     

PSA—Promoter of Stress and Anxiety or Providentially-Sent Antigen?

Measurement of serum prostate-specific antigen (PSA) levels has revolutionised all aspects of the management of men with prostate cancer. As well as monitoring established disease, PSA testing has an important role in the early detection of prostate cancer. Although some men will undoubtedly benefit from early detection and treatment, concerns are raised by the poor specificity of the PSA test and the lack of conclusive evidence that early detection and treatment of prostate cancer carries survival benefits. As men become more aware of PSA testing through both the media and the Internet, clinicians are being placed under increasing pressure to carry it out. This review explores the arguments for and against PSA screening in asymptomatic men.     

How to improve prostate biopsy detection of prostate cancer

The combination of serum prostate-specific antigen (PSA) testing and transrectal ultrasonography is a highly effective strategy to diagnose prostate cancer at an early curable stage. Even though PSA is the most useful serum biomarker to aid in prostate cancer detection, it has limited specificity: as many as 75% of men who undergo prostate biopsy because of an elevated PSA do not have prostate cancer. Additionally, sextant prostate biopsies miss prostate cancer at least 20% of the time. To reduce the number of false-negative biopsies, many have advocated obtaining 12 or more cores in a single biopsy session. Studies have shown that this practice is safe and can enhance cancer detection modestly. Although it is unlikely that prostate cancer imaging will replace prostate biopsy in the near future, many exciting new imaging technologies should eventually improve targeting of prostate needle biopsy and reduce false-negative biopsies. Some of the most exciting areas include power Doppler sonography, microbubble intravenous ultrasound contrast agents, and magnetic resonance spectroscopy. These functional imaging modalities can assess tumor blood flow and metabolic activity at a cellular level and can detect malignant changes that may not be detected by standard anatomic imaging.     

Predicting the probability of significant prostate cancer in Japanese men with serum prostate‐specific antigen less than 10 ng/mL: Development of a novel pre‐biopsy nomogram

Objectives: To develop and assess a new nomogram incorporating pre‐biopsy clinical data to predict significant prostate cancer in Japanese men with a serum prostate‐specific antigen (PSA) level of less than 10 ng/mL. Methods: We collected pre‐biopsy data from 620 men with a serum total PSA of less than 10 ng/mL. They included 491 men with a negative biopsy and 129 men who were confirmed to have histological prostate cancer and subsequently underwent radical prostatectomy. Clinically significant tumors were defined as those with a tumor volume larger than 0.5 mL and/or a Gleason score of 7 or more. Results: One hundred and seven prostatectomy patients had clinically significant cancers. Stepwise multivariate logistic regression analysis showed that digital rectal examination findings, PSA adjusted for transition zone volume and free‐to‐total PSA ratio were the significant independent predictors of significant cancers (P < 0.0001). Using these pre‐biopsy independent factors, a nomogram was developed to predict significant cancers. According to a receiver operating characteristics analysis, the nomogram showed an area under the curve of 0.831. Conclusion: This represents the first nomogram to predict the probability of clinically significant cancers before biopsy. This tool is most likely to be useful in the management of patients with moderate to elevated PSA.     

Who’s too old to screen? Prostate cancer in elderly men

Introduction:

Prostate cancer is the most common nonskin malignancy affecting men and is the second leading cause of cancer-related death in North America. The incidence of prostate cancer increases dramatically with age. However, many health authorities advocate the cessation of routine prostate cancer testing in men older than 75 because of the belief that most patients will have a clinically insignificant cancer and will not benefit from therapy. The true prevalence of clinically significant prostate cancer in elderly men is not known.

Methods:

We analyzed 1446 needle biopsies of the prostate in men aged 75 or older. All pathological reviews were conducted by the pathology department at the Methodist Hospital in Houston, Tex. Data were collected from pathology reports, hospital and clinic databases, and medical records when available. Data obtained included age at biopsy, serum prostate-specific antigen (PSA) levels, number of positive core biopsies and Gleason grade. Statistical analysis was performed using Stata. Clinically significant cancer was defined by the pathological presence of Gleason grade 6 adenocarcinoma in more than 1 biopsy core or the presence of any Gleason 4 or 5 component in the biopsy.

Results:

The median age of the patients included in the study was 78.8 and 95% of the patients were between the ages of 75 and 85. The mean serum PSA level for patients biopsied was 10.4 μg/L. Of all biopsies reviewed, 53% were positive for prostate cancer and 78% of these would be defined as clinically significant cancer. Regression analysis revealed age to be a significant (p < 0.05) factor for increased Gleason grade in positive biopsies. Logistic regression revealed age as a significant factor (p < 0.05) for clinically significant prostate cancer even when controlling for PSA. A serum PSA threshold value of 6.5 μg/L would have missed 38% of significant cancers and a threshold of 4.0 μg/L would have missed 8% of significant cancers.

Conclusion:

Our findings suggest that the prevalence of clinically significant prostate cancer in the elderly population may be higher than previously thought. As the population continues to live longer and healthier lives, it will become more common to confront prostate cancer morbidity in the eldery population. Using higher serum PSA thresholds to eliminate unnecessary biopsies in older men does not appear to help identify patients at greater risk of having clinically significant prostate cancer. Patients with prostate cancer having aggressive clinical features may benefit from treatment of their prostate cancer well into their eighth and ninth decades of life. Testing and diagnostic recommendations should reflect the potential benefit of identifying patients with aggressive prostate cancer even after age 75.