Prostate Carcinoma In Men Research Articles

Multiparametric MRI and MR Spectroscopic Imaging of Prostate Lesions with Implementation of PI-RADS and Histopathological Correlation: A Prospective Analysis

Introduction Majority of the elderly male population suffers from prostatism due to enlargement of the prostate as a result of what is now regarded as male climacteric. For standardizing multiparametric magnetic resonance imaging (MRI) of the prostate, the European Society of Urogenital Radiology published Prostate Imaging Reporting and Data System (PI-RADS) in 2012. Magnetic resonance spectroscopic imaging (MRSI) uses a strong magnetic field to obtain metabolic information that identifies the relative concentrations of various metabolites in the cell cytoplasm and the extracellular space. Prostate carcinoma is associated with proportionately lower levels of citrate and higher levels of choline and creatine than are seen in benign prostatic hyperplasia (BPH) or in normal prostate. This difference can be detected by MRSI. Aim This study has been undertaken with the objective of finding how reliable MRI is in establishing the diagnosis of lesions of prostate and to correlate the histopathological (HPE) findings of transrectal ultrasound (TRUS)–guided targeted prostate biopsy with the PI-RADS scoring (Version 2) on MRI in patients. Also, the study evaluates the accuracy of MRSI in the detection of prostatic carcinoma in men with elevated prostate-specific antigen (PSA) levels. Materials and Methods A prospective study was undertaken at a tertiary care hospital during a period of 2 years from May 2017 to April 2019 on 50 patients with PSA > 4 ng/dL and with palpable lesion on digital rectal examination. MRI and MRSI were performed with a 1.5-Tesla body MRI system. The pelvic phased-array coil was used for both excitation and signal reception. Imaging was done using standard protocols. Histological material was obtained from prostate chippings from transurethral resection of prostate. Results Fifty patients with elevated PSA levels underwent MRI, MRSI, TRUS-guided biopsy and documented PI-RADS scores. Eight patients had PI-RADS 1 score, 2 patients had PI-RADS 2 score, 8 patients had PI-RADS 3 score, 14 patients had PI-RAD 4 score, and 18 patients had PI-RADS 5 score. Thirty-two patients with PI-RADS 4 and PI-RADS 5 on imaging showed positive for malignancy on HPE, showing significant association on Chi-square test with X2 = 16.412 and p < 0.001 (statistically significant). MRSI detected 36 patients on biopsy proven cases of carcinoma (sensitivity 89.5%, specificity 64%, and accuracy 88%). Conclusion This study showed a very good correlation between positivity of prostate carcinoma on HPE and higher PI-RADS (4 and 5, respectively). PI-RADS overall score had 94% sensitivity compared with components such as diffusion-weighted imaging (DWI, 78%) and T2 hypointensity (72%). MRSI is more sensitive and specific compared with T2-weighted images alone.

An Unusual Cause of Hematuria: Primary Bladder Melanoma in an Older Man

To the Editor: Primary malignant melanoma of the bladder is rare; malignant melanomas of the bladder are usually metastatic lesions.1, 2 A recent review indicated 24 confirmed cases of metastatic melanoma of the bladder.1 Other papers reported another 27 postmortem cases of melanoma with bladder metastases.3 Because most of these autopsy cases were of asymptomatic subjects, the real incidence of secondary involvement of the bladder might be higher than generally estimated.4 The main symptom of bladder melanoma is gross hematuria.4 The diagnosis of metastatic melanoma of the bladder is often delayed and does affect the prognosis. Twenty-six cases of primary melanoma of the bladder have been reported.4 We report a case of primary bladder melanoma without involvement of other sites. In January 2015, an 81-year-old man was admitted to the Geriatrics Unit for an episode of gross hematuria in the previous month in the absence of any symptoms. His medical history included hypertension, hypothyroidism treated with L-thyroxine, peripheral arterial disease, and corneal transplantation at the age of 74. Urine cytology identified atypical cells, but analysis was not conclusive. He underwent cystoscopy, with evidence of three exophytic lesions, on which multiple biopsies were performed. Histology revealed groups of neoplastic cells with focal intracytoplasmatic melanin pigmentation. Immunohistochemistry revealed positivity for HMB45, melanoma antigen recognized by T cells 1 (MART-1), and S-100, and a diagnosis of bladder melanoma was made. At a further cutaneous examination, two nevi were detected and surgically removed; both were dysplastic without any sign of melanoma. Positron emission tomography–computed tomography did not reveal any further neoplastic site. Gastrointestinal endoscopy was also negative. Ophthalmic examination with fundus oculi exam did not indicate retinal melanoma. Radical cystectomy with ileal conduit was performed. Anatomical and histological examination showed two ulcerated lesions (2.5 and 1 cm in diameter, respectively) on the posterior wall. The lesions showed a proliferation of epithelioid-like cells characterized by ample eosinophilic cytoplasm, nuclear irregularity, and pleomorphism, with conspicuous nucleolus and arranged in solid nests. The neoplasia involved the mucosa and muscular and adipose tissue of the bladder wall. Pigment deposits were also present in the neoplastic tissue. Immunohistochemistry was performed using the streptavidin biotin method. Immunohistochemical analysis showed positivity of neoplastic cells for HMB45 and MART1 and focally for S100 protein, confirming the diagnosis of malignant melanoma (Figure 1). Prostate cancer with a Gleason score of 7 (4 + 3) was also diagnosed. During the postoperative course, the man experienced wound dehiscence, sepsis, and respiratory insufficiency. At his and his family's wishes, because of his age and comorbidity, no further therapies were administered. After 12 months, he was still alive, independent in activities of daily living, and disease free. Primary malignant melanoma is uncommon in the genitourinary tract, especially in the bladder.5 Age at presentation of primary bladder melanoma ranges from 7 to 91 (59 ± 17).4 The origin of malignant melanoma in the bladder is unclear. According to the ectopic theory, melanocytes would migrate from the neural crest through the mesenchyme toward the skin and hair follicles, possibly stopping in ectopic locations, including a developing bladder.6 Another hypothesis is that argyrophil urothelial cells are derived from urothelial stem cells with differentiation in the direction of neoplastic melanocytes.7 In the absence of a clinical history of melanoma, other lesions with an infiltrative growth pattern and similar cytomorphology may be considered. The possible list of differential diagnoses includes high-grade urothelial carcinoma, prostatic carcinoma in men, Mullerian carcinomas in women, lung carcinoma, breast carcinoma, and rare entities such as paraganglioma and sarcomatoid carcinoma.8 There is no consensus regarding the best treatment for the management of primary malignant melanoma of the urinary bladder, perhaps because of the small number of reported cases. The prognosis with primitive malignant melanoma is poor.4 Trials involving treatment options aimed at increasing survival and improving quality of life are urgent. From this perspective, this case report seems of special interest because the man described, although frail and multimorbid, successfully underwent major surgery. He was disease free and in good clinical status after 1 year. In conclusion, this case report shows that bladder melanoma, although rare, should be suspected at any age and may be amenable to radical treatment even in very old and frail individuals. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: AL, RG: study and data analyses. AL, RP, RAI: drafting the manuscript. AL, CT, GM, RAI: study design. All authors read and approved the final manuscript. Sponsor's Role: None.

Neutrophil-to-lymphocyte ratio predicts prostatic carcinoma in men undergoing needle biopsy

Neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammatory response, has been demonstrated as an independent prognosticator for some solid malignancies, including prostate cancer. In the present study, we evaluated the role of NLR in men who underwent prostate needle biopsy for their initial diagnosis of prostatic carcinoma. Both complete blood counts and free/total (F/T) prostate-specific antigen (PSA) ratio were examined in a total of 3,011 men in our institution. Of these, 1,207 had a PSA level between 4 and 10 ng/mL, and 357 of 810 who subsequently underwent prostate needle biopsy were found to have prostatic adenocarcinoma. NLR value was significantly higher in men with PSA of ≥ 20 ng/mL than in those with PSA of < 20 ng/mL (p < 0.001). NLR was also significantly higher in men with positive biopsy than in those with negative biopsy (p < 0.001). Using NLR cut-off point of 2.40 determined by the AUROC curve, positive/negative predictive values of NLR alone and NLR combined with F/T PSA ratio (cut-off: 0.15) were 56.6%/60.8% and 80.7%/60.1%, respectively. Multivariate analysis revealed that not only F/T PSA ratio (HR = 3.13) but also NLR (HR = 2.21) was an independent risk factor for prostate cancer. NLR is thus likely elevated in patients with prostate cancer. Accordingly, NLR, with or without combination with F/T PSA ratio, may function as a new biomarker to predict prostate cancer in men undergoing prostate needle biopsy.

Nasopharyngeal carcinoma and Dermatomyositis: a case report

Nasopharyngeal carcinoma has long been reported as the predominant type of cancer associated with dermatomyositis in many several Asian countries, including Hong Kong, Singapore, and Southern-Cina. Dermatomyositis is one of the idiopathic inflammatory myopathies showing characteristic cutaneous manifestations. Reviews from the western literature have demonstrated that certain cancers, such as ovarian and breast carcinoma in women and lung and prostate carcinoma in men, are highly associated with DM relative to the general population. We report the case of a Caucasian Italian patient with nasopharyngeal carcinoma and dermatomyositis. Considering the rarity of nasopharyngeal carcinoma among whites, both the detection and the report of each new case are noteworthy in defining the geographic and ethnic distribution of this tumor.

Abstract 2406: Molecular characterization of ciclooxigenase-2 in canine proliferative inflammatory atrophy of the prostate

Abstract Due to the importance and incidence of prostatic carcinoma in man, some animals are being used as a model in the investigation of the pathogenesis and development of this lesion. Similarly to men, the dog presents a spontaneous development of prostate cancer, which is locally invasive and can develop bone metastasis. Proliferative inflammatory atrophy (PIA) is considered a pre-neoplastic lesion in men. Overexpression of COX-2 has been associated with PIA, PIN and prostatic carcinoma playing a role in angiogenesis, apoptosis inhibition, increasing of invasive capacity, metastasis and inflammation in different prostatic affections. The aim of this study was to assess the protein and gene expression of COX-2 in laser capture microdissected stroma and epithelial cells of PIA foci in canine prostate by immunohistochemistry (IHC) and qRT-PCR. For IHC, 38 PIA lesions arranged in a tissue microarray were evaluated. Frozen fragments from 17 PIA and 3 normal prostatic tissues were used for COX2 gene expression. Our results showed increased COX2 gene expression in stromal cells compared to epithelial cells. High level of COX-2 protein expression was observed in 87% of PIA lesions, despite epithelial or stromal compartment. The In the present study, the stroma presented an important role, since the COX-2 gene expression in canine PIA lesions was increased in this cell compartment. To the best of our knowledge, this is the first report of COX2 gene expression in canine PIA. Since high levels of COX-2 have been associated to the risk of developing of prostate cancer in man, dog can be used as a natural model for this disease. The stroma can act as paracrine way in the epithelial cells, stimulating epithelial proliferation, reducing the apoptosis of this compartment and promoting angiogenesis in the microenvironment, factor that contribute to prostatic carcinogenesis and that the protein expression is increased in this lesion. Sponcer: Fapesp (Fundação de Apoio a Pesqusia do Estado de São Paulo) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2406. doi:10.1158/1538-7445.AM2011-2406

Combined magnetic resonance imaging and spectroscopy in the assessment of high grade prostate carcinoma in patients with elevated PSA: A single-institution experience of 356 patients

Purpose To assess the ability of combined whole-prostate magnetic resonance imaging and magnetic resonance spectroscopy imaging (MRI + MRSI) to predict the presence or absence of high grade (Gleason 4 + 3 or higher) prostate carcinoma in men with elevated PSA. Materials and methods Between March 2002 and September 2007, 356 subjects (mean serum PSA 11.5 ng/ml, range 0.4–133.0 ng/ml) were examined with fast-T2-weighted magnetic resonance imaging (MRI) and 3D-magnetic resonance spectroscopy imaging (MRSI) on a 1.5 T scanner. Prostate cancer was histopathologically proven in 220 patients (41 with high grade and 179 with lower grade cancer) and non-evidence of cancer was determined after at least 12 months (mean 21 months) clinical follow-up in 136 subjects. The sensitivity, false positive rate, and negative predictive value of MRI + MRSI were calculated using histopathology and follow-up results as reference standard. Results MRI + MRSI had a significantly higher sensitivity for high grade tumors (92.7%) than for lower grade tumors (67.6%), and was false positive in only 7.4% of patients with non-evidence of prostate cancer. For exclusion of a high grade tumor, MRI + MRSI had a negative predictive value of 98.4%. Conclusions MRI + MRSI holds great potential for predicting presence or absence of high grade tumors in men with elevated PSA. This can be important in the selection of patients for active surveillance, or in the decision to rebiopsy patients with prior negative biopsies.

MR-based biomarkers in the diagnosis and the evaluation of the therapeutic response to radiotherapy (ETRR) in prostatic carcinoma (PCa): Implementation of clinical and experimental approaches

e16136 Background: ETRR in PCa remains a challenging task. New biomarkers in the form of metabolites, detected with Proton Magnetic Resonance Spectroscopy (1H-MRS), and quantitative Apparent Diffusion Coefficient (ADC), determined with Diffusion-Weighted Magnetic Resonance Imaging, could be of value in the ETRR for PCa. Methods: Twenty-one men with biopsy proven localized PCa were examined before external radiotherapy. 3D-1H-MRS was performed at 3.0T without endorectal coils. The delivered radiotherapy dose was 78 Gy in 39 fractions with 6 MV photons. MR follow-up examinations up to 36 months post-radiotherapy were performed. For the pre-clinical study, healthy rat prostate was studied in 3 nude rats. PC3-MM2 and PAC-120 tumors were subcutaneously (SC) and orthotopically (OT) xenografted in 5 nude rats, respectively. Radiotherapy anti-tumor efficacy administered as HDR-brachytherapy (SC) or X6 external beam irradiation (OT) delivering 10 Gy/5 fractions was evaluated. 1H-MRS was performed at 4.7 T using SVS. Results: Twelve men received the 3-month examination, 8 patients are at 6-months, 4 are at 9 months and 1 has been followed for 1 year. At baseline, healthy prostate shows a low Choline (Cho)/Citrate ratio, whereas the presence of cancer considerably increases this ratio. At 3 months, we observed metabolic atrophy except for Cho. Although, higher ADC values are normally found in peripheral zone than in central gland, these differences disappear after radiotherapy. In healthy rat prostate high levels of Cho without citrate were noted. Cho and free lipids were detected in PC3-MM2 and PAC120 SC-grafted tumors, with a higher Cho content in PC3-MM2. Radiotherapy induced significant antitumor activity in PC3-MM2 (SC) (T/C% = 38%) and OT (ILS% = 58%) tumors, but was not efficient in PAC120 SC-grafted tumors (T/C% = 90%). Radiotherapy slightly modified Cho content 4 days after the end of treatment but no modification on overall metabolic profile was observed before, during and after radiotherapy. Conclusions: Combined ADC and Cho are powerful biomarkers for the detection of PCa in men and could be useful for ETRR.The use of Cho in ETRR for PCa in rats appears to be promising. No significant financial relationships to disclose.

Prevention of Bone Mineral Loss by Zoledronic Acid in Men with Prostate Carcinoma Receiving Androgen Deprivation Therapy: A Prospective Randomized Trial in an Indian Population

Objective: To assess the efficacy of zoledronic acid in preventing bone mineral loss in locally advanced, non-metastatic prostate carcinoma in men receiving androgen deprivation therapy. Patients and Methods: Forty-one men with locally advanced, non-metastatic prostate carcinoma were randomly divided into 2 groups to receive zoledronic acid 4 mg intravenous infusion (n = 19) or a placebo (n = 22) every 3 months. The primary efficacy variables were measurement of bone mineral density (BMD) of the lumbar spine and urinary deoxypyridinoline at the baseline and at the end of treatment. The efficacy analysis was by mean and percent-age change of these variables from the baseline to the end of the treatment. Results: The mean BMD increased significantly to 1.18 g/cm² from a baseline value of 1.09 g/cm² in the zoledronic acid group. In the placebo group, the mean BMD decreased to 0.99 g/cm² from a baseline value of 1.07 g/cm². The percentage change of BMD of the lumbar spine from the baseline was an 8.15% increase in the zoledronic acid group and a 7.0% decrease in the placebo group. There was also a significant decrease of mean urinary deoxypyridi-noline values in the zoledronic acid group (p < 0.05) and a significant increase in the placebo group (p < 0.001). Conclusion: Long-term androgen deprivation therapy for prostate carcinoma patients leads to significant loss of bone density. Bisphosphonate treatment especially with the highly potent zoledronic acid should be considered in patients with a low BMD baseline because this drug not only prevents the decrease in BMD but also improves BMD.

Ratio of prostate specific antigen minor molecular forms-to-total prostate specific antigen is constant regardless of the pathological condition of the prostate.

We assessed 3 molecular forms of prostate specific antigen (PSA) prospectively to determine the real proportion of the nonfree, nonalpha1-antichymotrypsin complex form of PSA-to-total PSA and evaluated the clinical significance of its various forms. We prospectively assessed 1,878 serum samples from 994 subjects for total PSA, free PSA and PSA-alpha1-antichymotrypsin complex (ACT). Nonfree, nonPSA-ACT PSA (minor form PSA) was calculated as the difference between total PSA and the sum of free PSA plus PSA-ACT complex. The proportion of the minor form PSA was approximately 20% to 25% of total PSA at any range of total PSA, whereas that of free PSA and PSA-ACT decreased and increased, respectively, in correlation with the increment of total PSA. There was no significant difference in the percent of minor form PSA in patients with prostatic carcinoma and those with benign prostatic status. The proportion of minor form PSA was constant, while the percent of free PSA and PSA-ACT increased and decreased, respectively, in accordance with total PSA regression after hormonal therapy for prostatic carcinoma. PSA-ACT was judged to be superior to total PSA for distinguishing prostatic carcinoma in men with PSA 2 to 10 ng./ml. by ROC analysis. Approximately a fourth of total PSA consists of minor forms of complexed PSA. The average proportion of minor form-to-total PSA was constant at various levels of total PSA and at any prostatic status of patients. PSA-ACT was superior to total PSA for the early detection of prostatic carcinoma.

New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.

Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma

An effect of fatty acids has been implicated in men with advanced-stage prostate carcinoma and in men who have died of the disease. To evaluate the influence of fatty acids in men with prostate carcinoma at earlier stages, the authors examined the relation between prostatic concentrations of fatty acids and locally advanced prostate carcinoma in men with clinically organ-confined disease. Fatty acids were measured by capillary gas chromatography in fresh, nonmalignant prostate tissue specimens collected during surgery from 196 men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided, two-sample Student t tests compared mean concentrations in men with extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined disease. Logistic regression accounted for clinical stage, prostate-specific antigen level, Gleason sum, and other factors. Percent total prostatic polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95% confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003). Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent arachidonic acid also were found to be inversely related to the risk of seminal vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,; 0.75-0.95; P=0.005, respectively). Prostatic PUFA levels appear to influence the risk of locally advanced prostate carcinoma in men with clinically organ-confined disease. This association may be mediated through the immune system.

Prostate carcinoma among men with human immunodeficiency virus infection.

Several malignancies are known to occur more frequently in individuals with human immunodeficiency virus (HIV) infection. To determine the incidence of prostate carcinoma in men with HIV infection, the authors initiated a prostate carcinoma screening program in a large HIV clinic. Beginning in February 2002, monitoring of prostate-specific antigen (PSA) levels and digital rectal examination (DRE) were included in the routine annual health maintenance provided to men with HIV infection age > or = 35 years who were followed in the infectious disease clinic at the Naval Medical Center San Diego. All men with prostate carcinoma in this population over the last 2 years were reviewed. Demographic data (age, ethnicity), duration of HIV infection, laboratory values (CD4 counts and HIV viral load), and medication use were determined by medical record review. Men with elevated PSA levels (levels above age-adjusted PSA values or PSA velocity > or = 0.75 ng/mL per year) or abnormal DRE results were referred for urologic evaluation. Comparisons between groups were performed using a logistic regression model and the Fisher exact test. Multivariate analysis was performed by logistic regression to determine relations between prostate carcinoma and patient characteristics. Two hundred sixty-nine men age > or = 35 years (mean age, 43.4 years; range, 35-72years) underwent prostate carcinoma screening by DRE, and 216 men also received PSA testing. Overall, 56.3% of the patients were white, 28.7% were African American, and 15% were of other racial ethnicity. Of the 216 men, 7 (3.2%) had elevated PSA values, and none had abnormal DRE results. Three patients were diagnosed with prostatitis (PSA range, 3.3-25.7 ng/mL), and 1 patient had high-grade prostatic intraepithelial neoplasia, which was determined after a biopsy was performed. Repeat PSA evaluations were within normal limits for the remaining three patients. Review of the cohort during the 2-year period before the current study was initiated revealed 5 additional cases of prostate neoplasia. Prostate carcinoma was common (4 of 11 men, 36.4%) in men age > 60 years and occurred with relatively preserved CD4 counts (mean, 509 cells/mm(3)). In multivariate analysis, African-American race (P = 0.020) and duration of HIV infection (P = 0.047) were found to be associated with the development of prostate carcinoma. Prostate carcinoma screening identified abnormal PSA values in 3.2% of the HIV-positive cohort, many associated with prostatitis. Prostate carcinoma was common in older men and was associated with duration of HIV infection. As the life expectancy of men with HIV infection increases, prostate carcinoma screening will become increasingly important in this population.

Gonadotropin-releasing hormone antagonists: impact of IVF practice and potential non-assisted reproductive technology applications.

To provide the clinician with updated knowledge of the most recent findings on the clinical use of gonadotropin-releasing hormone antagonists. Gonadotropin-releasing hormone antagonists, which have recently been introduced in clinical practice, cause an immediate suppression of gonadotropin secretion by competitive blocking of pituitary gonadotropin-releasing hormone receptors. Thus, they are effective in preventing the premature luteinizing hormone surges during ovarian stimulation for in-vitro fertilization and may improve the patient's response to lower doses of gonadotropins. Better patient acceptance, shorter treatment cycles and fewer follicles and oocytes are also reported. Data existing so far concerning the necessity of luteal phase support after the use of gonadotropin-releasing hormone antagonists show that it might not be mandatory when used in clomiphene citrate costimulated cycles or in intrauterine insemination cycles. The use of gonadotropin-releasing hormone antagonists seems to be safe for pregnant women and their offspring. All sex-hormone-dependent disorders, currently treated with gonadotropin-releasing hormone agonists, may in future be indications for a gonadotropin-releasing hormone antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. The vast majority of the available clinical data up till now, however, are in assisted reproduction and prostate cancer. It is expected that the availability of gonadotropin-releasing hormone antagonist will lead to the use of 'softer' ovarian stimulation protocols, which will be shorter, cheaper and safer compared with the conventional protocols.

Ratio Of Prostate Specific Antigen Minor Molecular Forms-To-Total Prostate Specific Antigen Is Constant Regardless Of The Pathological Condition Of The Prostate

We assessed 3 molecular forms of prostate specific antigen (PSA) prospectively to determine the real proportion of the nonfree, nonalpha1-antichymotrypsin complex form of PSA-to-total PSA and evaluated the clinical significance of its various forms. We prospectively assessed 1,878 serum samples from 994 subjects for total PSA, free PSA and PSA-alpha1-antichymotrypsin complex (ACT). Nonfree, nonPSA-ACT PSA (minor form PSA) was calculated as the difference between total PSA and the sum of free PSA plus PSA-ACT complex. The proportion of the minor form PSA was approximately 20% to 25% of total PSA at any range of total PSA, whereas that of free PSA and PSA-ACT decreased and increased, respectively, in correlation with the increment of total PSA. There was no significant difference in the percent of minor form PSA in patients with prostatic carcinoma and those with benign prostatic status. The proportion of minor form PSA was constant, while the percent of free PSA and PSA-ACT increased and decreased, respectively, in accordance with total PSA regression after hormonal therapy for prostatic carcinoma. PSA-ACT was judged to be superior to total PSA for distinguishing prostatic carcinoma in men with PSA 2 to 10 ng./ml. by ROC analysis. Approximately a fourth of total PSA consists of minor forms of complexed PSA. The average proportion of minor form-to-total PSA was constant at various levels of total PSA and at any prostatic status of patients. PSA-ACT was superior to total PSA for the early detection of prostatic carcinoma.

Long term follow‐up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4.0 ng/ml or less

BACKGROUND Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. METHODS Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. RESULTS Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. CONCLUSIONS It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0–4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL. Cancer 2001;91:744–51. © 2001 American Cancer Society.

Long term follow-up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4.0 ng/ml or less

Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0-1.9, and 2.0-4.0 ng/mL, respectively. It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0-4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL.

Cancer in the very elderly Dutch population

BACKGROUND Cancer incidence and mortality rates rarely are studied in people age > 85 years. Usually, patients ages 65 years, 75 years, and 85 years of age are combined into 1 group because of small numbers. The number of people age ≥ 85 years in the Netherlands increased from 99,000 in 1976 to 203,000 in 1995 (an increase of 105%). The growth of the total population in this period was only 13%. This study addressed cancer incidence and mortality rates among the very elderly in the Netherlands. METHODS Cancer mortality data (1976–1995) and population data were obtained from Statistics Netherlands, whereas cancer incidence data (1989–1995) were provided by the Netherlands Cancer Registry. Cancer incidence and mortality rates were calculated and trends in cancer mortality were studied. RESULTS Total cancer incidence rates were highest in the age group 85–94 years, in men and women (3466/100,000 person-years and 1604/100,000 person-years, respectively). Prostate carcinoma was the most frequent cancer in men ages 85–94 years, followed by colorectal carcinoma. In women ages 85–94 years, colorectal carcinoma was most frequent, closely followed by breast carcinoma. In the 95+ years age group squamous cell skin carcinoma was the most frequent cancer in both men and women, followed by prostate carcinoma in men and breast carcinoma in women. Cancer mortality rates increased with increasing age to nearly 3700/100,000 person-years in men age 95+ years and 2500/100,000 person-years in women age 95+ years. In men, lung carcinoma was the most frequent cancer-related cause of death in patients age ≤ 85 years, whereas in older men this applied to prostate carcinoma. In women, breast carcinoma was the most frequent cancer-related cause of death in all age groups > 55 years. Cancer as a cause of death became less prominent with increasing age. Over the period 1991–1995, 42% of deaths in men ages 55–64 years were attributed to cancer versus 52% of deaths in women (total population); these proportions in the 95+ years age group were 11% and 7%, respectively. CONCLUSIONS Peak incidence rates of major cancers were found in the very elderly population in the Netherlands. Different trends in age specific mortality rates of individual cancer sites were found, with stable rates in the middle age groups and increasing rates in the oldest age groups. This may reflect a real increase caused for instance by changes in mortality from other diseases and/or an artifactual increase caused by increased cancer detection rates in the (very) elderly. Cancer 2000;89:1121–33. © 2000 American Cancer Society.

Cancer in the very elderly Dutch population.

Cancer incidence and mortality rates rarely are studied in people age > 85 years. Usually, patients ages 65 years, 75 years, and 85 years of age are combined into 1 group because of small numbers. The number of people age > or = 85 years in the Netherlands increased from 99,000 in 1976 to 203,000 in 1995 (an increase of 105%). The growth of the total population in this period was only 13%. This study addressed cancer incidence and mortality rates among the very elderly in the Netherlands. Cancer mortality data (1976-1995) and population data were obtained from Statistics Netherlands, whereas cancer incidence data (1989-1995) were provided by the Netherlands Cancer Registry. Cancer incidence and mortality rates were calculated and trends in cancer mortality were studied. Total cancer incidence rates were highest in the age group 85-94 years, in men and women (3466/100,000 person-years and 1604/100,000 person-years, respectively). Prostate carcinoma was the most frequent cancer in men ages 85-94 years, followed by colorectal carcinoma. In women ages 85-94 years, colorectal carcinoma was most frequent, closely followed by breast carcinoma. In the 95+ years age group squamous cell skin carcinoma was the most frequent cancer in both men and women, followed by prostate carcinoma in men and breast carcinoma in women. Cancer mortality rates increased with increasing age to nearly 3700/100,000 person-years in men age 95+ years and 2500/100,000 person-years in women age 95+ years. In men, lung carcinoma was the most frequent cancer-related cause of death in patients age < or = 85 years, whereas in older men this applied to prostate carcinoma. In women, breast carcinoma was the most frequent cancer-related cause of death in all age groups > 55 years. Cancer as a cause of death became less prominent with increasing age. Over the period 1991-1995, 42% of deaths in men ages 55-64 years were attributed to cancer versus 52% of deaths in women (total population); these proportions in the 95+ years age group were 11% and 7%, respectively. Peak incidence rates of major cancers were found in the very elderly population in the Netherlands. Different trends in age specific mortality rates of individual cancer sites were found, with stable rates in the middle age groups and increasing rates in the oldest age groups. This may reflect a real increase caused for instance by changes in mortality from other diseases and/or an artifactual increase caused by increased cancer detection rates in the (very) elderly.

Evaluation of needle biopsy in the diagnosis of prostatic carcinoma in men with prostatic intraepithelial neoplasia

Correspondence to Mr Christopher R. Chapple, Urology Research Department, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. Tel: +44 114 271 2791; fax: +44 114 279 8318 Royal Hallamshire Hospital, Sheffield, UK

Evaluation of needle biopsy in the diagnosis of prostatic carcinoma in men with prostatic intraepithelial neoplasia.

Prostatic intraepithelial neoplasia (PIN) is considered a premalignant lesion of the prostate. It is often encountered in prostate needle biopsy in cases where no cancer is identified. In order to evaluate its importance 25 patients with PIN in a former prostate needle biopsy underwent a second ultrasound guided needle biopsy. The first biopsy was performed in all patients as a result of positive DRE. In 13 patients (52%), prostate cancer was identified in the second specimen. All presented with high or intermediate grade PIN in the first biopsy. PSA values were compared with PIN grade and cancer presentation in the second biopsy, although no statistically significant difference was proven. In conclusion, when PIN is discovered in prostate needle biopsy in patients with positive DRE, a second biopsy has to be performed in order to exclude the possibility of a prostate carcinoma.