Incidentally Detected Adenocarcinoma Prostate in Transurethral Resection of Prostate Specimens: a Hospital Based Study from India

Background: Awareness about prostate cancer has increased in the community, and prostate cancer screening examinations, including prostate specific antigen (PSA) assays, are now widely available. Prior to the PSA era, up to 27% of prostate cancers were detected incidentally at the time of transurethral resection of prostate (TURP). After PSA testing became widely available, the incidence of incidentally detected carcinoma prostate in TURP specimens without prior diagnosis reduced to 5-13%. However, the incidence of incidentally detected carcinoma prostate has been reported to vary across the globe since various factors can influence the identification of this malignancy in TURP specimens. In this paper, we focus on rates of incidentally detected prostate cancer in TURP specimens in our hospital and correlate it with various parameters. Materials and Methods: This retrospective study of histopathological findings of biopsy specimens was conducted for patients undergoing TURP during a period of 5 years from April 2010. The inclusion criteria were patients diagnosed with benign prostatic hyperplasia (BPH) (digital rectal examination (DRE) not showing any abnormally hard areas and normal age adjusted PSA values). Patients with elevated PSA, abnormal DRE, documented urinary tract infection and proved adenocarcinoma prostate (CaP) were excluded from the study. The total weight of prostatectomy specimen, occurrence of carcinoma prostate in the chips, percentage of total tissue resected showing malignancy and Gleason's scores were recorded. Results: A total of 597 patients belonging to the inclusion criteria were studied. The incidence of occult CaP in the study group was 5.2 % (31/597). Out of these, 8 belonged to T1a and 23 belonged to T1b stages. The age group 70 - 79 years had the maximum incidence of occult CaP. It was observed that the clinical grading of prostate did not have a bearing on the incidence of occult CaP whereas the weight of resected specimen correlated with the incidence of CaP. The incidence of occult CaP was greater with low volume prostates ( < 20 g). (P=0.15). Conclusions: The rate of incidentally detected adenocarcinoma prostate in patients undergoing TURP for clinically diagnosed BPH was found to be only 5.2 % in our study which is low when compared with similar studies done elsewhere. The age of the patient and weight of the resected specimen correlated with incidence of occult prostate cancer. The clinical grading of prostate by DRE however, demonstrated no correlation.     

血清缓激肽与前列腺癌的相关性研究

目的 探讨血清缓激肽在前列腺癌的诊断及鉴别诊断中的临床应用价值.方法 收集68例前列腺癌患者和32例前列腺增生患者,以同期体检的健康男性32例为对照组,收集其血清,酶联免疫吸附试验(enzymelinked immuno sorbent assay,ELISA)法检测血清中的缓激肽水平,比较各组血清缓激肽水平的差异以及前列腺癌患者在不同年龄、临床分期、病理分期(Gleason评分)、前列腺特异抗原(prostate specific antigen,PSA)水平、肿瘤体积以及骨转移、淋巴结转移、局部侵犯与否状态下血清缓激肽水平的差异.比较血清缓激肽与PSA联合诊断前列腺癌和PSA独立诊断前列腺癌的敏感度差异.结果 前列腺癌组血清缓激肽水平[(16.44 ±0.91) μg/L]低于对照组[(19.72±1.10) μg/L]和前列腺增生组[(20.93±1.80) μg/L],差异均具有统计学意义(均P＜0.05).在肿瘤体积较大的前列腺癌患者血清缓激肽水平较低(P＜0.05),而血清缓激肽水平在年龄、肿瘤临床分期、病理分期(Gleason评分)、PSA水平及骨转移、淋巴结转移、局部侵犯与否方面比较差异均无统计学意义(均P＞0.05).血清缓激肽与PSA联合诊断前列腺癌较单独诊断敏感度提高(P＜0.05).结论 前列腺癌患者血清缓激肽表达水平较低,且与肿瘤体积相关.血清缓激肽与PSA联合诊断前列腺癌敏感度较单独诊断高.     

Serum osteoprotegerin levels are increased in patients with advanced prostate cancer.

PURPOSE: Osteoprotegerin (OPG) is a soluble osteoclastogenesis inhibitor that regulates bone turnover. We reported recently that OPG protein expression is significantly increased in prostate cancer (CaP) cells present in bone metastases. The aim of this study was to determine serum OPG levels in patients at different stages of CaP and correlate the results with disease status. EXPERIMENTAL DESIGN: OPG levels were examined in patients with benign prostatic hyperplasia, clinically localized CaP, early recurrence of CaP, and advanced CaP and evidence of bone metastases. Serum OPG levels were measured by sandwich ELISA assays. The serum Crosslaps (sCTX) assay was used to quantify bone resorption in the advanced CaP group. RESULTS: Serum OPG levels were increased significantly in the advanced CaP group versus all other groups. There was no significant correlation between serum OPG levels and PSA levels either in the advanced CaP group or within any of three treatment subclasses of this group: no Tx, those not treated; Tx, those treated; and R, those treated with resorption blockers. Levels of OPG were negatively correlated with sCTX levels only in the advanced CaP Tx group. sCTX levels correlated with prostate-specific antigen levels in the advanced CaP Tx and R groups but not in the no-Tx group. CONCLUSIONS: Our data show that serum OPG levels are increased with advanced CaP. We hypothesize that OPG levels are related to CaP progression and suggest that further studies of the biological effects of OPG on CaP metastases are warranted.     

Elevation of cytokine levels in cachectic patients with prostate carcinoma

BACKGROUND: Approximately 60-70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1), IL-6, and IL-8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFalpha, IL-1beta, IL-6, and IL-8. METHODS: The levels of TNFalpha, IL-1beta, IL-6, IL-8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ-confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total-PSA assays were used to determine cytokine and PSA levels, respectively. RESULTS: Levels of TNFalpha, IL-6, and IL-8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFalpha were correlated positively with IL-8, and there was no correlation between PSA levels and any of the cytokine levels. IL-1beta levels were below the limit of detection in all samples. CONCLUSIONS: The current results show that levels of TNFalpha, IL-6, and IL-8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia.     

The usefulness of serum human kallikrein 11 for discriminating between prostate cancer and benign prostatic hyperplasia

Prostate-specific antigen (PSA) is the most useful tumor marker for diagnosis and monitoring of prostate cancer (CaP). Recently, we developed a specific immunoassay for human kallikrein 11 (hK11), one of the kallikrein gene family members, and found that hK11 was highly expressed in prostatic tissue and could be detected in seminal plasma (E. P. Diamandis et al., Cancer Res., 62: 295-300, 2002). The aim of this study was to investigate whether serum hK11 levels could be used to discriminate CaP from benign prostatic hyperplasia (BPH). We analyzed for hK11, total PSA, and percentage of free PSA, 150 serum samples from men with histologically confirmed BPH (n = 64) or CaP (n = 86). Total and free PSA levels were measured by the Immulite PSA assay, and hK11 levels were measured by our previously published immunofluorometric assay. Serum hK11 levels and the hK11:total PSA ratio were both significantly lower in CaP patients than in BPH patients. In the subgroup of patients with percentage of free PSA less than 20, an additional 54% of BPH patients could have avoided biopsies by using the hK11:total PSA ratio. Receiver operating characteristic (ROC) curve analysis demonstrated that the hK11:total PSA ratio [area under the curve (AUC), 0.83] and percentage of free PSA (AUC, 0.83) were much stronger predictors of CaP than total PSA (AUC, 0.69). These preliminary data suggest that the hK11:total PSA ratio could be a useful tumor marker for CaP and could be combined with percentage of PSA to further reduce the number of unnecessary prostatic biopsies.     

Prostate cancer epidemiology in a rural area of North Western Greece

Epirus is a rural area of North-Western Greece. We reviewed data from 4 hospitals for 4.975 patients who underwent prostate biopsy in Epirus in the twelve year period from 1999 to 2010. Two six-year periods were compared (1999-2004 and 2004-2010). All cases of prostate cancer confirmed by biopsy were recorded and age-standardized incidence rates per 100,000 males were calculated. We also recorded the clinical stage for patients diagnosed in our hospital and correlated this with PSA and Gleason scores. Percentage of positive prostate biopsies was also calculated. There were a total of 1714 new cases during 1999-2010 and the mean annual age-adjusted incidence was 34/100,000. The mean incidences during 1999-2004 and 2005-2010 were 26/100,000 and 42/100,000, respectively. The mean age at diagnosis was 74. The most common Gleason score was 6 and the prevalent clinical stage was T2. Median PSA at diagnosis was 10.8 ng/ml. There was a significant difference between stage cT4 and all other stages regarding PSA value (p=0.000). A positive correlation was found between Gleason score and PSA (p=0.013). These results are in accordance with the incidence rise recorded in neighboring countries of South-East Europe. However we should keep in mind the risk of overdiagnosis and the detection of low-risk cancers that would not have caused morbidity or death during a man's lifetime anyway.     

Serum soluble Fas level for detection and staging of prostate cancer

To evaluate the clinical usefulness of measuring serum soluble Fas (sFas) for differentiation between prostate cancer and benign prostate hyperplasia (BPH) and for staging of prostate cancer, serum sFas and PSA were determined in 38 and 20 men with prostate cancer and BPH, respectively, before treatment. In 17 patients, sFas and PSA were measured one hour after transrectal ultrasound-guided sextant biopsy in order to examine the leakage of sFas into the circulation after prostatic injury. Patients with prostate cancer had a significantly higher level of sFas than those with BPH. The serum sFas level was statistically elevated in patients with metastatic prostate cancer. There was a statistically significant correlation between sFas and PSA in patients with prostate cancer but not in those without cancer. The serum sFas did not change one hour after systematic prostatic biopsy although PSA levels were markedly elevated. sFas levels might be useful as a discriminator between prostate cancer and BPH while sFas might indicate the tumor burden in patients with prostate cancer.     

Detection of human chorionic gonadotrophin-beta in serum or urine of prostate cancer patients is of no clinical significance.

The aim of this study was to prospectively evaluate the potential role of elevated urinary/serum human chorionic gonadotrophin-beta (hCGbeta) in prostate cancer prognosis. 104 patients with newly diagnosed prostate cancers were included; 68 patients had organ-confined, 18 had locally advanced and 18 had metastatic disease. A control group consisted of 115 patients presenting with benign prostatic disease. Serum and urinary total hCGbeta was measured prior to treatment and serum PSA was measured at diagnosis. The patients were treated along conventional lines and progression-free survival was assessed. Four patients had elevated serum and 10 had elevated urinary, total hCGbeta. There were no significant correlations between serum/urinary levels of hCGbeta and tumour stage, Gleason score or PSA. In contrast, serum PSA had significant linear correlations with both clinical tumour stage and Gleason score (p = 0.0001). At a median follow-up of 36 months, 22 (21.2%) patients had died while 17 (16.3%) others had progressed. Kaplan-Meier plots and log-rank test revealed no significant difference in progression-free survival between patients with elevated or normal levels of serum and/or urinary total hCGbeta. Clinical tumour stage, grade and PSA were statistically significant prognostic variables. Immunoassay measurement of serum or urinary hCGbeta has no significant role in the clinical management of prostate cancer.     

Prostate Cancer Incidence in Turkey: An Epidemiological Study

Background: This study aimed to determine the incidence of prostate cancer in Turkey in a population-basedsample, and to determine clinical and pathological characteristics of the cases. Materials and Methods: Allnewly diagnosed prostate cancer patients were included in this national, multi-centered, prospective and noninterventionalepidemiological registry study conducted in 12 cities representing the 12 regions of Turkey fromJuly 2008 to June 2009. The population-based sample comprised 4,150 patients with a recent prostate cancerdiagnosis. Results: Age-adjusted prostate cancer incidence rate was 35 cases per 100,000 in Turkey. At the timeof diagnosis, median age was 68, median PSA level was 10.0 ng/mL. Digital rectal examination was abnormal in36.2% of 3,218 tested cases. Most patients had urologic complaints. The main diagnostic method was transrectalultrasound guided biopsy (87.8%). Gleason score was ≤6 in 49.1%, 7 in 27.8% and >7 in 20.6% of the cases.There was a statistically significant positive correlation between serum PSA level and Gleason score (p=0.000).The majority of patients (54.4%) had clinical stage T1c. Conclusions: This is the first population-based nationaldata of incidence with the histopathological characteristics of prostate cancer in Turkey. Prostate cancer remainsan important public health concern in Turkey with continual increase in the incidence and significant burdenon healthcare resources.     

Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives

Genetic predisposition accounts for >/=10% of all cancer of the prostate (CaP) and is therefore considered a major risk factor, together with age and ethnic origin. Several epidemiological studies have suggested that familial clustering of CaP may be associated with an increased frequency of breast and other cancers among relatives. In order to correlate the incidence of CaP with prevalence of breast and other cancers, we have performed uni- and multi-variate analyses on 691 complete pedigrees including probands, who were consecutive patients with confirmed CaP treated in three French urological departments. We have shown a significantly higher risk (RR = 2.3, p = 0.01) to develop breast cancer in families with multiple than in those with a single CaP. Risk of observing other types of cancer within these families was not significant. We then calculated the breast cancer risk in early onset prostate cancer families, and observed a relative risk that is even more significant (RR = 5.5, p = 0.002). Furthermore, the risk was >30 times that a proband's mother have breast cancer if CaP occurred below 55 years of age, rather than after 75 years (p = 0.003). This study has therefore shown for the first time, the relatively high penetrance for breast cancer in relatives of early onset CaP patients.     

A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.     

The Relationship of PSA, PSAD and Clinicopathological Stage in Patients with Prostate Cancer

OBJECTIVE To investigate the relationship between the clinicopatho- logical stage and serum prostate specific antigen(PSA)concentration and PSAdensity(PSAD)in patients with prostate cancer. METHODS The clinicopathological stage was determined on the basis of a pathological examination and clinical data in 65 prostate cancer patients treated by radical prostatectomy.PSA and PSAD were measured before the operation.The Spearman rank correlation was applied to evaluate the relationship between the clinicopathological stage,serum PSAconcentration and PSAD. RESULTS Patients with higher PSA and PSAD were significantly more likely to have higher clinical stages,a higher Gleason score,positive surgical margins,capsular penetration,and seminal vesicle invasion(each P<0.05). But there was no significant association between PSA and lymph node metastasis(P=0.053).The levels of serum PSA concentration and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients. CONCLUSION The level of both PSA and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients.But PSAD may be a more powerful predictor of clinical stage and prognosis than PSA.     

Serum proteomic patterns for detection of prostate cancer

Pathologic states within the prostate may be reflected by changes in serum proteomic patterns. To test this hypothesis, we analyzed serum proteomic mass spectra with a bioinformatics tool to reveal the most fit pattern that discriminated the training set of sera of men with a histopathologic diagnosis of prostate cancer (serum prostate-specific antigen [PSA] > or =4 ng/mL) from those men without prostate cancer (serum PSA level <1 ng/mL). Mass spectra of blinded sera (N = 266) from a test set derived from men with prostate cancer or men without prostate cancer were matched against the discriminating pattern revealed by the training set. A predicted diagnosis of benign disease or cancer was rendered based on similarity to the discriminating pattern discovered from the training set. The proteomic pattern correctly predicted 36 (95%, 95% confidence interval [CI] = 82% to 99%) of 38 patients with prostate cancer, while 177 (78%, 95% CI = 72% to 83%) of 228 patients were correctly classified as having benign conditions. For men with marginally elevated PSA levels (4-10 ng/mL; n = 137), the specificity was 71%. If validated in future series, serum proteomic pattern diagnostics may be of value in deciding whether to perform a biopsy on a man with an elevated PSA level.     

血清PSA及超声引导穿刺活检对前列腺癌病理分期预测价值研究

目的 研究血清前列腺特异性抗原(PSA)及超声引导穿刺活检对前列腺癌病理分期的预测价值.方法 选取200例经直肠超声引导前列腺穿刺活检确诊为前列腺癌的患者的临床资料进行研究.分析患者的血清PSA、穿刺活检阳性百分数及Gleason评分3个参数与前列腺癌病理分期的相关性;同时对比性分析以上3个参数在不同病理分期前列腺癌患者中的差异情况.结果 血清PSA、穿刺活检阳性百分数及Gleason评分均与前列腺癌患者的病理分期呈正相关(P﹤0.001);D期前列腺癌患者的血清PSA水平明显高于A期、B期、C期前列腺癌患者(P﹤0.05),而A期、B期、C期前列腺癌患者的血清PSA水平两两之间比较,差异均无统计学意义(P﹥0.05);C期与D期前列腺癌患者的穿刺活检阳性百分数比较,差异无统计学意义(P﹥0.05),而其他各分期间穿刺活检阳性百分数两两比较,差异均有统计学意义(P﹤0.05);A期与C期、B期与C期、A期与D期、B期与D期前列腺癌患者的Gleason评分比较,差异均有统计学意义(P﹤0.05),而A期与B期、C期与D期前列腺癌患者的Gleason评分比较,差异无统计学意义(P﹥0.05).结论 血清PSA、穿刺活检阳性百分数及Gleason评分均可单独用于前列腺期病理分期的预测,同时该3个参数在区分前列腺癌病理分期方面也发挥一定辅助作用.     

Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p <.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.     

Low doses of oral dexamethasone for hormone-refractory prostate carcinoma

BACKGROUND: Although glucocorticoids have been used to treat patients with hormone-refractory prostate carcinoma (HRPC), reports have varied regarding the types and doses of glucocorticoids used as well as their clinical benefits. In the current study, low doses of dexamethasone were investigated for their specific beneficial effects and the feasibility of long term treatment. METHODS: Thirty-seven patients diagnosed with HRPC were treated with oral dexamethasone (0.5-2 mg/day). The patients ranged in age from 53-89 years (median, 74 years). Thirty-two patients, including 6 with lymph node metastases, had bone involvement whereas only 5 patients were found to have elevated serum prostate specific antigen (PSA) levels. RESULTS: Twenty-three patients (62%) who received no other concomitant therapy demonstrated a decline in their serum PSA level of > or = 50%, which was confirmed by a second PSA value obtained > or = 4 weeks later. The median time to PSA progression was 9 months. Among 18 patients with bone pain, 11 (61%) had improvement and in 5 patients (28%) the pain became stable. Among 21 patients with interpretable bone scans, 4 (19%) showed improvement and 8 (38%) achieved stable disease. Both symptomatic and objective responses of bone metastases were correlated with declines in the serum PSA level of > or = 50%. Ten patients achieved an increase in their hemoglobin level of at least 2 g/dL. Patients whose PSA level declined by > or = 50% with therapy had significantly prolonged survival (median, 22 months). As pretreatment markers, a longer interval before the initial evidence of disease progression appeared was found to correlate significantly with posttherapy PSA declines of > or = 75%. All side effects of the glucocorticoids were reported to be mild. CONCLUSIONS: Low doses of dexamethasone were found to be beneficial in the treatment of HRPC, decreasing the severity of anemia and osseous disease as well as reducing serum PSA levels. A posttherapy serum PSA decline of > or = 50% appears to be a reliable marker of improved survival with this therapy.     

Nationwide treatment patterns and survival of older patients with prostate cancer

Objectives

To examine the clinical features, applied treatments, and survival of older patients with prostate cancer compared with younger patients.