What is the role of androgen deprivation therapy in the treatment of locally advanced prostate cancer?

This Practice Point commentary discusses the paper by Horwitz and colleagues, which reported the long-term results of the RTOG 92-02 trial in which patients with locally advanced, node-negative prostate cancer who were treated with neoadjuvant-concurrent hormone ablation therapy and external beam radiation therapy (70 Gy) were subsequently randomized to receive either no further androgen deprivation or long-term (2-year) goserelin therapy. The results at 10 years confirm biochemical and clinical outcome benefits with the use of long-term androgen deprivation therapy for patients treated with conventional-dose radiotherapy. How these results should best be incorporated into dose-escalated radiotherapeutic approaches remains unclear, however, and this issue requires further investigation.     

What is the best strategy of hormonal therapy in the treatment of locally advanced prostate cancer?

We retrospectively studied patients with clinical stage C-D1 prostate cancer in Gifu University and affiliated hospitals. The overall survival rate of patients treated with hormonal therapy after radical prostatectomy was superior to that of patients treated with hormonal therapy alone. This result was remarkable in the patients under 76 years old with clinical stage C. A PubMed search of the literature on various randomized controlled trials revealed that the overall survival rate of patients treated with hormonal therapy alone was inferior to that treated with adjuvant hormonal therapy. We recommend prospective evaluation of combined therapy including prostatectomy, radiotherapy and hormonal therapy for the patient with a risk factor such as high Gleason score.     

Is a digital rectal examination necessary in the diagnosis and clinical staging of early prostate cancer?

OBJECTIVE: To assess the role of a digital rectal examination (DRE) in the clinical diagnosis of prostate cancer and in predicting the pathological stage, as the diagnosis of early prostate cancer usually comprises prostate-specific antigen (PSA) testing, a DRE and transrectal ultrasonography (TRUS)-guided biopsies. PATIENTS AND METHODS: Over the 4 years between 2000 and 2004, 408 consecutive patients (mean age 63.8 years) referred with age-specific PSA levels of 2.5-10.0 ng/mL and who had a TRUS-guided 12-core prostate biopsy were included in the study. They had a DRE by either of two experienced consultant urologists. The results of the DRE and core biopsy histology were compared with the histology and the radical prostatectomy specimen in a subset (82 men) of the study population. RESULTS: Cancer was detected on biopsy in 152 patients; of the 196 with an abnormal DRE, 47% had cancer on biopsy. In the patients with a normal DRE, 59 cancers were detected. Men with cancer were older and had a higher median PSA level. There was no correlation between the DRE and biopsy findings, and none between an abnormal DRE and histological diagnosis of cancer. Of the patients who had a radical prostatectomy, 38% had a normal DRE. CONCLUSION: There was no correlation between the DRE, biopsy findings and pathological staging. The DRE did not contribute to managing patients with prostate cancer, but this does not mean that there is no longer a place for the DRE in assessing the urological patient. If patients are appropriately counselled before PSA testing, a DRE may not be essential for patients with a PSA level of 2.5-10 ng/mL.     

Transrectal ultrasound biopsy of the prostate: does it still have a role in prostate cancer diagnosis?

Transrectal ultrasound (TRUS) guided biopsy of the prostate has been a standard diagnostic approach for prostate cancer over the past thirty years. Today, the role of TRUS biopsy is being challenged by transperineal (TP) prostate biopsy due to concerns over the safety and diagnostic yield of TRUS biopsy. TRUS biopsy still offers a convenient, reliable and accessible tool for diagnosing prostate cancer in the majority of patients. It continues to play a role in prostate cancer diagnosis, especially where hospital resource allocation is limited, including the public sector. TRUS biopsy has low rates of severe complications, although there remains room for improvement in current practice to improve the tolerability and reduce the incidence of post-biopsy infection.     

What’s new in the field of prostate cancer chemoprevention?

Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.     

What about lombo-aortic curage in the treatment of testicle cancer?

The indications and techniques of retroperitoneal lymphadenectomy in stage I non seminomatous germ cell tumours have markedly evolved over the past ten years. A literature review allows noticing that historical radical retroperitoneal dissection has been replaced by more limited techniques, known as nerve sparing and nerve preserving lymph node dissection. Stage I non seminomatous germ cell tumours are classified according to the risk of retroperitoneat lymph node involvement; they constitute three groups: low, intermediate and high risk tumours. Retroperitoneal lymph node dissection is considered for low risk patients in case of non compliance or difficult follow-up, and for intermediate risk patients (vascular invasion with presence of high percentage of teratomatous component).     

The PCA3 test for guiding repeat biopsy of prostate cancer and its cut-off score： a systematic review and meta-analysis

The specificity of prostate-specific antigen （PSA） for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 （PCA3） may be more accurate in outcome prediction than other methods for the early detection of prostate cancer （PCa）. However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis （with or without inclusion of high-grade prostatic intraepithelial neoplasia （HGPIN） and atypical small acinar proliferation （ASAP））. Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, specificities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios （ORs） were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve （AUCs） of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.     

Alpha-linolenic acid and the risk of prostate cancer. What is the evidence?

PURPOSE: Several studies have examined the association between polyunsaturated fatty acids and prostate cancer risk. We evaluated the evidence on the association between the essential polyunsaturated fatty acid, known as alpha-linolenic acid, and the risk of prostate cancer in humans. MATERIALS AND METHODS: We comprehensively reviewed published studies on the association between alpha-linolenic acid and the risk of prostate cancer using MEDLINE. RESULTS: A number of studies have shown a positive association between dietary, plasma or red blood cell levels of alpha-linolenic acid and prostate cancer. Other studies have demonstrated either no association or a negative association. The limitations of these studies include the assumption that dietary or plasma alpha-linolenic acid levels are positively associated with prostate tissue alpha-linolenic acid levels, and measurement errors of dietary, plasma and red blood cell alpha-linolenic acid levels. CONCLUSIONS: More research is needed in this area before it can be concluded that there is an association between alpha-linolenic acid and prostate cancer.     

What is the molecular pathology of low-risk prostate cancer?

Objectives  Low-risk prostate cancer is defined as a clinical T1c or T2a tumor with a Gleason score of ≤6 and PSA <10 ng/ml. This is a pretreatment diagnosis and the patient can turn out to have either significant or insignificant disease. With methods currently available in practice it may not be possible to differentiate between these groups. Numerous molecular pathological changes have been described in prostate carcinoma. This review was to evaluate which of these changes may be useful to distinguish the group of patients likely to have significant carcinoma within the low risk category. Materials and methods  The literature on molecular pathology of prostate cancer was reviewed using MEDLINE and reference lists of relevant publications focusing on early and late molecular events and available molecular biomarkers in prostate cancer. Results  There are a variety of molecular markers with the potential to be clinically utilized for assessment of low risk prostate cancer. One of the most promising is TMPRSS2: ETS fusion, which is a homogeneous event occurring early in prostate carcinogenesis. Other promising markers include p27, EZH2 and c-MYC. Conclusions  FISH analysis or RT-PCR based assays to detect TMPRSS2: ETS fusion and immunohistochemical assessment of p27, EZH2 and c-MYC may become useful ancillary tests in patients with low risk prostate cancer. Some serum biomarkers have promise for future use. Large prospective studies followed by clinical trials are necessary before these molecular markers could be integrated into clinical practice.     

What’s in a name? What constitutes the clinical diagnosis of osteoporosis?

Osteoporosis is a skeletal disorder in which reductions in bone strength predispose to an increased risk for fractures. Currently, the diagnosis is officially made based exclusively on bone mineral density T-scores that are ≤-2.5 at the spine or hip. Limiting the clinical diagnosis of osteoporosis solely to a T-score-based criterion, which is the official convention in the USA, creates uncertainty about the use of the term osteoporosis to diagnose older women and men who have T-scores >-2.5, but either have already sustained low-trauma fractures or are recognized as having high fracture risk based on absolute fracture risk calculations from FRAX or other algorithms. A failure to diagnose such patients as having osteoporosis may be one component of the well-documented underdiagnosis and undertreatment of this disease which limits our ability to reduce the burden of fractures worldwide. There is a need to expand the criteria for making a clinical diagnosis and to codify these changes in order to help patients, physicians, policy makers, and payers better understand who has this disease and the elevated risk for fracture that it represents.     

What next after hormonotherapy in cancer prostate?

Treatment of hormone-resistance cancer prostate (HRCP) is undergoing evolution. Chemotherapy is now increasingly being utilized. The steps involved in the hormone management and the role for chemotherapy in the current time are being discussed. Hormonal management is carried out at different stages of hormonal sensitivity by sequential hormonal use. Once hormonal resistance is established, the combination of mitoxantrone and prednisone become a standard chemotherapeutic approach. New agents, such as docetaxel, are being tested in phase-III trials against mitoxantrone plus prednisone. HRCP is now regarded as a chemotherapy-sensitive tumor. The goals of chemotherapy in HRCP are to decrease PSA level and improve quality of life. New agents and combinations are needed to improve survival to meet this end.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Time between diagnosis and surgical treatment on pathological and clinical outcomes in prostate cancer: does it matter?

Introduction

Prostate cancer (PC) most of the time presents with an indolent course. Thus, delays in treatment due to any causes might not affect long-term survival and may not affect cancer cure rates.

Purpose

In this study, we evaluated the effect of delay-time between PC diagnosis and radical prostatectomy regarding oncological outcomes: Gleason score upgrade on surgical specimen, pathologic extracapsular extension (ECE) on surgical specimen, and postoperative biochemical recurrence (BCR) on follow-up.

Methods

We evaluated PC patients who underwent radical prostatectomy (RP) regarding clinical and pathological findings and theirs respective interval between diagnosis and surgical treatment measured in days and months. We used univariate and multivariate logistic regression to evaluate the impact of interval-time.

Results

A total of 908 PC patients underwent RP between 2006 and 2014. Mean age was 61.5 years, the mean time-to-surgery was 191 days (>?6 months) and 187 (20.5%) patients had BCR, with a mean follow-up of 44 months. According to our analysis, no statistically significant maximum cut-off time interval between diagnostic biopsy and surgery could be established (p?=?0.215). Regardless of interval-time:?≤?6 months (56.5%), 6–12 months (38.5%), and?>?12 months (5.1%) after biopsy, we found no time interval correlated with poor oncological outcomes. This study has several limitations. It was retrospective and had a mean follow-up of 4 years. Additional follow-up is necessary to determine whether these findings will be maintained over time.

Conclusions

We showed that the time between diagnosis and surgical treatment did not affect the oncological outcomes in our study.

     

Role of 5α-reductase inhibitors in prostate cancer prevention and treatment

Although testosterone is the most abundant serum androgen, dihydrotestosterone is the main prostatic androgen. Testosterone is converted to dihydrotestosterone by the enzyme 5α-reductase (5α-R). Dihydrotestosterone plays an important role in several human diseases, including benign prostate enlargement and prostate cancer. The observation that males born with 5α-R 2 deficiency have never been reported to develop prostate cancer stimulated interest in development of 5α-R inhibitors. Thus far, 2 5α-R inhibitors are approved for clinical use. Several trials evaluated the use of 5α-R inhibitors in prostate cancer prevention and treatment and will be reviewed in this article.