The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3b What's known on the subject? and What does the study add? The optimal method of active surveillance in prostate cancer remains unknown. This study is one of the first to report on the role of transperineal template prostate biopsies in active surveillance. It demonstrates that around one third of men are reclassified with more significant prostate cancer at an early stage in their management. This is a higher proportion than reported in contemporary cancers using standard transrectal biopsies for restaging.

OBJECTIVE

• ? To evaluate the role of transperineal template prostate biopsies in men on active surveillance.

PATIENTS AND METHODS

• ? In all, 101 men on active surveillance for prostate cancer underwent restaging transperineal template prostate biopsies at a single centre.
• ? Criteria for active surveillance were ≤75 years, Gleason ≤3+3, prostate‐specific antigen (PSA) ≤15 ng/mL, clinical stage T1–2a and ≤50% ultrasound‐guided transrectal biopsy cores positive for cancer with ≤10 mm of disease in a single core.
• ? The number of men with an increase in disease volume or Gleason grade on transperineal template biopsy and the number of men who later underwent radical treatment were assessed.
• ? The role of PSA and PSA kinetics were studied.

RESULTS

• ? In all, 34% of men had more significant prostate cancer on restaging transperineal template biopsies compared with their transrectal biopsies.
• ? Of these men, 44% had disease predominantly in the anterior part of the gland, an area often under‐sampled by transrectal biopsies.
• ? In the group of men who had their restaging transperineal template biopsies within 6 months of commencing active surveillance 38% had more significant disease.
• ? There was no correlation with PSA velocity or PSA doubling time.
• ? In total, 33% of men stopped active surveillance and had radical treatment.

CONCLUSIONS

• ? Around one‐third of men had more significant prostate cancer on transperineal template biopsies.
• ? This probably reflects under‐sampling by initial transrectal biopsies rather than disease progression.

     

Age-specific reference levels of serum prostate-specific antigen and prostate volume in healthy Arab men

OBJECTIVE; To determine age-specific reference ranges for serum prostate-specific antigen (PSA) concentration and prostate volumes in a population of healthy Arab men. SUBJECTS AND METHODS: Blood samples were taken from 396 healthy Arab men (from Kuwait and Oman) aged 15-79 years and from across the social spectrum. Men aged >40 years had a digital rectal examination and transrectal ultrasonography of the prostate to determine prostate volume. The serum PSA level was measured using commercial kits, and age-specific ranges for PSA levels and prostate volume determined. RESULTS: The serum PSA ranges (ng/mL) for each age range in Arab men were: 40-49 years, 0-0.9; 60-69, 0-2.7; 70-79, 0-5.5 ng/mL; the respective prostate volumes were 8-22, 9-30 and 10-33 mL. The serum PSA level and prostate volume correlated with age (P < 0.001). Arab men had lower serum PSA levels and prostate volumes than those reported for Caucasians, but similar to those reported for Asians (Japanese and Chinese). CONCLUSION: These results indicate that Arab men have lower PSA levels and prostate volumes than Caucasians. The levels are slightly lower than those reported in the Japanese and, as in the Japanese, low PSA levels and small prostate volumes might be related to the low incidence of clinical prostate cancer in Arab men.     

Evaluation of magnetic resonance imaging-based prostate-specific antigen density of the prostate in the diagnosis of prostate cancer

OBJECTIVES: We evaluated prostate-specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS-based PSAD), magnetic resonance imaging (MRI; MRI-based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI-based PSATZD) in the diagnosis of prostate cancer (PCa). METHODS: One hundred and twenty patients, who were suspected to have PCa based on PSA, ranged between 4.1 and 20.0 ng/mL were enrolled in this study. RESULTS: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI by 11.4% in the patients with PSA levels ranging 4.1-20.0 ng/mL, 7.2% in those 4.1-10.0 ng/mL, and 15.7% in those 10.1-20.0 ng/mL, respectively. PSA levels were correlated with the prostatic volume estimated using TRUS and MRI, and TZ volume estimated using MRI in the patients without PCa; however, the level was not correlated with them in the patients with PCa. The area under the receiver operating characteristic curve of MRI-based PSAD was higher than that of TRUS-based PSAD; however, there was no statistical difference. Stepwise logistic regression analysis for the prediction of PCa by using PSA-related parameters confirmed that MRI-based PSATZD was the most significant predictor in patients with PSA levels in the range of 4.1-20.0 ng/mL (P < 0.001), the range of 4.1-10.0 ng/mL (P = 0.002), and the range of 10.1-20.0 ng/mL (P < 0.001), respectively. CONCLUSIONS: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI. MRI-based PSATZD is the most significant predictor in the four parameters.     

The distribution of serum prostate-specific antigen levels among American men: implications for prostate cancer prevalence and screening

BACKGROUND: The purpose of this study was to describe the distribution of serum prostate-specific antigen (PSA) among American men and to estimate the number of prevalent cases of biopsy detectable prostate cancer among men with normal serum PSA. METHODS: We analyzed data of the National Health and Nutrition Examination Survey 2001-2002 (NHANES 2001-2002) data and combined these results with published data from the Prostate Cancer Prevention Trial (PCPT). RESULTS: Most men in the US have a serum PSA < or = 4.0 ng/ml, and mean and median serum PSA values rise steadily with age. There are an estimated 1,607,585 (95% CI 1,370,848-1,844,322) prevalent cases of biopsy detectable prostate cancer in men aged 62-85 years with a serum PSA < or = 4 ng/ml. Among men aged 62-75 years, there are an estimated 1,252,143 (95% CI 1,054,677-1,449,609) prevalent cases, including an estimated 195,499 (95% CI 140,234-250,764) high-grade tumors. CONCLUSION: A large number of prevalent cases of biopsy detectable prostate cancer exist in American men with a normal PSA.     

Performance of prostate‐specific antigen mass in estimation of prostate volume in Japanese men with benign prostate hyperplasia

Objectives: Obese men with benign prostate hyperplasia might have lower serum prostate‐specific antigen because of hemodilution, resulting in underestimation of total prostate volume by serum prostate‐specific antigen. The aim of this study was to compare the performance of prostate‐specific antigen mass as the absolute amount of prostate‐specific antigen protein secreted into circulation with that of serum prostate‐specific antigen in the prediction of total prostate volume. Methods: A total of 1517 men with serum prostate‐specific antigen up to 10 ng/mL, including 1425 with biopsy‐proven benign prostate hyperplasia, were enrolled in this study. Height and weight were used to estimate body mass index, body surface area and plasma volume. Prostate‐specific antigen mass was calculated as serum prostate‐specific antigen multiplied by plasma volume. The association between serum prostate‐specific antigen or prostate‐specific antigen mass and transrectal ultrasound‐measured total prostate volume were evaluated by Pearson's correlation coefficient (Υ), linear regression analyses and receiver operating characteristic curves. Results: Serum prostate‐specific antigen had an inverse relationship with plasma volume, decreasing as plasma volume increased, after adjustment of total prostate volume. Larger total prostate volume per serum prostate‐specific antigen was found in men with higher body mass index or plasma volume. Among all participants, the correlation (Υ = 0.456) between prostate‐specific antigen mass and total prostate volume was apparently stronger than that (Υ = 0.442) between serum prostate‐specific antigen and total prostate volume. Prostate‐specific antigen mass outperformed serum prostate‐specific antigen at estimating total prostate volume cut‐off values of 30 and 40 mL. These findings were more significant in men aged ≥60 years. Conclusions: Prostate‐specific antigen mass performs better than serum prostate‐specific antigen in estimating TPV, especially in men aged ≥60 years.     

血清PSA密度在前列腺活检中的意义

目的 探讨血清ＰＳＡ密度（ＰＳＡＤ）在前列腺活检中的意义。方法 对１７３例血清ＰＳＡ升高，有阳性直肠指诊或异常直肠Ｂ超发现者，进行了前列腺活检。对血清ＰＳＡＤ与前列腺活检的关系进行分析。结果 １７３例活检的前列腺肿瘤阳性率为５０．３％（８７／１７３），其中前列腺癌８４例，肉瘤２例，移行细胞癌１例，当血清ＰＳＡ为４～２０ｎｇ／ｍｌ，ＰＳＡＤ〈０．１５时，其敏感性和特异性分别为１００．０％和０．０％；     

Quality of life in active surveillance for early prostate cancer

Recently, the prevalence of the prostate-specific antigen screening test for early-stage prostate cancer has increased, but this has also resulted in an increase in insignificant cancers. The treatment outcome of early-stage prostate cancer is excellent, but such a radical treatment also leaves the patient with undesired adverse consequences. To resolve such problems, attention should be paid to active surveillance as a modern treatment option. This study aimed to systematically review the literature about quality of life in prostate cancer patients undergoing active surveillance. Evidence was acquired from PubMed databases in March 2019 using quality of life, prostate cancer, well-being, anxiety, depression, stress, outcomes, active surveillance, radiation therapy and radical prostatectomy as keywords. Five clinical active surveillance studies measured health-related quality of life and related psychological factors, and seven compared active surveillance with other treatments (radical therapy and hormone therapy). Active surveillance was superior to radical therapy for urinary and sexual function. Furthermore, most patients who opted for active surveillance showed lower anxiety and fear of progression, whereas health-related quality of life was maintained. Although active surveillance has the advantage of being non-invasive, its diagnosis and follow-up protocols are unreliable. Because such uncertainty can affect patients’ quality of life, utilization of imaging modalities, such as magnetic resonance imaging, and the development of new biomarkers are required.     

Repeat prostate biopsies predict location of index cancer in an active surveillance cohort

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The accuracy of TRUS‐guided biopsies in identifying the location of an index cancer at surgery is low. When two biopsies show cancer in the same location, the concordance between the biopsy and surgical location of the cancer increases.

OBJECTIVE

? To evaluate the ability of repeat prostate biopsies to determine the location of the index cancer for men on prostate cancer surveillance.

PATIENTS AND METHODS

? Forty‐five men on active surveillance had a record of the locations of their positive diagnostic biopsy, repeat surveillance biopsy and index cancer (i.e. largest cancer) from prostatectomy specimens. ? Logistic regression analysis was used to evaluate the association between two consecutive needle biopsies showing cancer in an identical location and the outcome of finding the index cancer at the same location as the initial diagnostic biopsy.

RESULTS

? Eighteen of 45 (40%) men ultimately had an index cancer at the same location as their diagnostic biopsy. ? Thirteen men had two consecutive biopsies that showed cancer at the same location each time; nine of these men ultimately had an index cancer at that same location. ? In multivariable logistic regression analysis of men with at least two biopsies, having two initial consecutive biopsies with the same location increased the odds (odds ratio 5.9; 95% CI 1.1–31, P= 0.037) of having an index cancer at the same location as the initial biopsy in a cohort of men on active surveillance.

CONCLUSIONS

? A substantial proportion of men in an active surveillance cohort who undergo prostatectomy ultimately have evidence of an index cancer at the same location as their initial biopsy. ? This is more likely to be the case when a repeat biopsy shows evidence of cancer at the same location.     

Prostate-specific antigen adjusted for the transition zone volume versus free-to-total prostate-specific antigen ratio in predicting prostate cancer

BACKGROUND: We performed this study to assess the efficacy of prostate-specific antigen adjusted for the transition zone volume (PSATZ) and free-to-total prostate-specific antigen (PSA) ratio (F/T ratio) in predicting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasonography guided systemic sextant biopsies and had a PSA of 4.1-10.0 ng/mL. PSATZ was compared with F/T ratio via receiver operating characteristic (ROC) curves. RESULTS: Of 67 patients, 22 (32.8%) had prostate cancer and 45 (67.2%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSA density, F/T ratio and PSATZ were 7.96+/-2.01ng/mL, 0.28+/-0.14 ng/mL/cc, 0.10+/-0.06 and 0.70+/-0.28 ng/mL/cc in patients with prostate cancer and 6.39+/-1.68 ng/mL, 0.16+/-0.06 ng/mL/cc, 0.15+/-0.05 and 0.29+/-0.10 ng/mL/cc in patients with BPH, respectively. The ROC curve analysis demonstrated that PSATZ predicted the biopsy outcome significantly better than F/T ratio in all 67 patients (P<0.01) and in a subset of 53 men with normal digital rectal examination (P<0.01). With a cut-off value of 0.35 ng/mL/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ and F/T ratio may be useful in diagnosing prostate cancer with intermediate levels of PSA. Prostate-specific antigen adjusted for the transition zone volume is more accurate than F/T ratio in distinguishing benign prostatic disease from prostate cancer. But large prospective studies are required to assess the precise role of PSATZ and F/T ratio in early prostate cancer detection.     

Change in the ratio of free-to-total prostate-specific antigen during progression of advanced prostate cancer.

BACKGROUND: The ratio of free-to-total prostate-specific antigen (PSA) is different in benign prostatic hyperplasia and in the early stage of prostate cancer. The present study was undertaken to examine the ratio of free-to-total PSA in the advanced stage of this cancer and its subsequent change during course of the disease. METHODS: Free and total PSA were measured in sera collected from the following patients with benign and cancerous prostatic diseases: 47 cases of benign prostatic hypertrophy, nine in TIC with less than 10 ng/mL of total PSA, 11 in stage C, 16 in D2, 22 in remission under endocrine therapy, and 12 in relapse. In addition, PSA was measured sequentially in four other patients who were also in relapse. RESULTS: The ratio of free-to-total PSA was similar in early and advanced stages of untreated prostate cancer and was lower than that in benign prostatic hyperplasia. The ratio increased to the level of benign prostatic hyperplasia during remission from stages C and D2 under endocrine therapy. There was no correlation with the intervals from the start of the therapy to examination. Following relapse, the ratio came down gradually to the level obtained in untreated prostate cancer. CONCLUSION: The ratio of free-to-total PSA was similar in all stages of untreated prostate cancer. Response and relapse to endocrine therapy were associated with increase and decrease in ratio, respectively.     

Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models

BACKGROUND: Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS: The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS: Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600-2100 nM). The majority of this PSA is enzymatically active (i.e., 80-90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 +/- 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 +/- 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 +/- 9 nM) and LAPC-4 (7.3 +/- 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., approximately 18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS: Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete approximately 70-300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs.