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Too much
- Jean-Claude GRANGE (3 December 2007)
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Role of Prostate specific antigens(PSA) and PSA Kinetics in the screening, predictive outcome, & relapse in prostate carcinomas in community of Kolkata, W.B
- Professor pranab kumar Bhattacharya MD(cal) path, FIC Path(Ind), Bhattacharya RupakBsc(cal),Msc(JU)Purbapalli,Sodepur, kol-110, Bhattacharya Upasana DPSRubipark Kol,Bhattacharya Palash MD(PGT)Patho, Chakraborty Anindya MO Urosurg, Gyean Biplab MBBS Demon, Patho, Sinha S.K MD(chandigarh) Prof. Pathology, IPGMER Kol-20, (14 December 2007)
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Screening for prostate cancer in younger men
- NAZAR R DESSOUKI (15 December 2007)
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Jean-Claude GRANGE, General Practitioner Mantes-la-Jolie, France
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Sir, The paper by Lane and colleagues (1) confirm that urological community around the world thinks that men prostate is the personal property of urologists. Albeit a majority of governmental agencies -- and particularly in France (2) do not recommend screening for prostate cancer in the community by practising DRE and testing PSA urologists are persuaded that their ethics is to convince anybody that radical prostatectomy is better than epidemiological and interventional studies. Now, regarding these uninteresting data, and in the absence of evidence to guide clinicians about whether or not to screen men for prostate cancer I propose to test PSA in men aged 30 – 35 and to investigate the need for radical prostatectomy when PSA levels reach 1 ng/ml without any biopsies. The accumulation of false evidences and flaw data do not mean that it is mandatory to transform naive men in probably cancer patients. Yours, sincerely. JC GRANGE, MD 16, rue Blaise Pascal 78200 - Mantes-La-Jolie. FRANCE References : 1 - Lane J, Howson J, Donovan J, Goepel J, Dedman D, Down L, et al. Detection of prostate cancer in unselected young men: prospective cohort nested within a randomised controlled trial. BMJ 2007;335:1139-45 2 - Opportunité d’un dépistage systématique du cancer de la prostate par le dosage de l’antigène spécifique de prostate. ANAES, mai 1998, pp115. http://www.has- sante.fr/portail/upload/docs/application/pdf/psa3.pdf Competing interests: None declared |
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Professor pranab kumar Bhattacharya MD(cal) path, FIC Path(Ind), Professor of Pathology, incharge histopathology unit, incharge Blood Bank &VCTC, Cytogenetics IInstitute of Post Graduate Medical Education & Research,(IPGMER) 244a AJC Bose Road,Kol-20,W.BIndia, Bhattacharya RupakBsc(cal),Msc(JU)Purbapalli,Sodepur, kol-110, Bhattacharya Upasana DPSRubipark Kol,Bhattacharya Palash MD(PGT)Patho, Chakraborty Anindya MO Urosurg, Gyean Biplab MBBS Demon, Patho, Sinha S.K MD(chandigarh) Prof. Pathology, IPGMER Kol-20,
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With the ageing of global population, prostate cancer has becoming one of the most common malignancies amongst men. Prostate cancer is the major cause of death for cancer in men including also in India. The world standard age adjusted mortality rate in 1983 to 1992 was 2.8 per 105 people per year in Honkong to 20.8 per 105 in Sweden to 34.3 in USA black population [1]. Prostate cancer was the cause of death of more than 30,000 American men in the year 2001[3] In England 2725 newly diagnosed prostate cancer men were registered in cancer registry in 2000. Overall incidence of prostate cancer there is 98 per 105 men. In 2001 death from prostate cancer in England was 8396[2] Highest incidence of prostate cancer is found in Jamaican men. It is much higher then black American men. Greatest percentage of mortality from prostate cancer is usually seen in Asian Countries [2]. It is still the second most leading cause of mortality and morbidity amongst cancers diagnosed in men, after oral cancer, while lung cancer stands in 3rd position in men, in India including in West Bengal as per the tumor registry of India. In the USA, life time risk of a diagnosis of prostate cancer is 16% and risk of death is 3.4%. In India, in a 50 year old man with a further life expectancy of 25 years, there is 42% life time risk of having microscopic cancer of prostate. It is also a major burden of mortality in men through out world. The problem in the community appears as the patient’s age advances and as the aged people’s numbers gradually increasing in our society. Despite the complexities the evidence seems to indicate that mortality rates from prostate cancer are declining as a result of improved screening & treatment strategies. The successful management of prostate cancer requires so early detection systems, appropriate risk assessment and effective treatment responses. As a histopathologist the authors are related with screening & early diagnosis system of health services of West Bengal, India. Author’s experiences in prostate needle biopsies or in TRUP biopsies while working in histopathology section of IPGMER-Kolkata, the problem of prostate cancer comes before us usually at age group of 60-78years with a median age group of 65 years. However the Authors came across some times prostate cancer even at age group less than 50 years also in West Bengal. In 2 years [2006-07] TURP/TRUS biopsy of prostate chips sent to author’s unit only at pathology dept. of IPGMER, out of 64 cases, 4 cases were diagnosed as Prostatic intraepithelial Neoplasia[PIN] grade 1,(6.2 %) 5cases(7.8%) as PIN grade2 and 2 cases as PIN grade 3[3.1%] . Nodular hyperplasia of Prostate(NHP) with or without evidence of prostatities were diagnosed in 46 cases(71%), NHP with adenomatous hyperplasia in 1 case while adenocarcinoma in high Gleason’s scoring were found in 3(4.68%) cases only &were in range of 47-53 years. In USA also 30-40% of men aged< 50 years have prostate cancer but 8% of these men became clinically significant [3] Often the patient party, when receive our histopathological diagnosis of prostate cancer of their kin one, they are not often ready to accept such a diagnosis. Some times they come to us with a report of very low total PSA value, done from any private laboratory of the city of Kolkata or of district towns, which makes authors in a real dilemma to give the diagnosis of prostate cancer- Adenocarcinoma. A common question appears when the pre-operative total PSA value is within 2.6 ng/ml to 4 ng/ml, whether the patient has really prostate cancer or not? The author came across few cases of prostate cancer in with a total serum PSA value < 1ng/ml and were in real trouble to report positively that the patients had prostate cancer, though histopathology section showed either PIN grade3 or hypernephriod[ Gleason 7b] prostate adenocarcinoma. The other problem comes when the patients and patients party comes for follow up with serial total PSA value in post TRUP operation or post radiation period to comment for biochemical recurrence or metastasis happened or not? So a big question stands before the authors, how much total serum PSA value is specific and sensitive to diagnose a prostate cancer in the earliest stages and how much is its value in the predictive or prognostic out come of the followed up patients? Is there any other good markers then PSA? Or whether the sensitivity and specificity of PSA can be increased to detect an early cancer? PSA is a serum marker that is central to the diagnosis and management of prostate cancer amongst the uro-surgeons of West Bengal and of India. Serum total PSA measurement have been widely accepted amongst urologist and other General Physicians as a tool for use in screening for prostate cases and in the follow-up of disease after treatment in West Bengal as well as in India. However chemical significance of an elevated total serum PSA value especially in range of 4---10ng/ml is debatable and controversial, as per authors. Estimation of Total Serum PSA is bread and butter of Pathologists& of private laboratories. However increase of PSA can be due to nodular hyperplasia or a malignant disease and quest still continues for a more sensitive and specific marker. However successful decline in morbidity and mortality from prostate cancer results from improved screening and treatment strategies. Total PSA is commonly used for detecting prostate cancer and monitoring treatment responses. The wide spread use of PSA in USA was followed by a sharp increase of prostate cancer diagnosis and a steady decline in associated morbidity. This is due to earlier detection of prostate cancer. However it has been also documented and postulated that routine PSA screening can do more harm than good. PSA testing is the minimally invasive procedure with a positive test has a sensitivity [who has disease 70-80%, when a threshold level of 4ng/ml is reported [4]. The specificity of PSA [the number of men with a negative test among men without prostate cancer] is not as favorable as it’s sensitivity as per author’s experience. The best sensitivity rates reported in the literature are 60-70%[5]. The rate was now ever achieved, only when men with a history of surgery for nodular hyperplasia of prostate were excluded from the study . The positive predictive value (PPV) of PSA is the number of true positives among all positive tests and are around 30-42%[6] in men with a PSA value between 4.1ng/ml and 10ng/ml and is further lowered to 13%-27% in men with PSA value between 2.6ng/ml to 4 ng/ml. Some authors pointed out that there is no clinical useful relationship between preoperative serum PSA value in range 2ng/ml to 10 ng/ml and volume or grade of prostate cancer [7]. This is because that most PSA leakage from prostate from prostate into serum comes from the Transition Zone (TZ) of prostate [4]. So before the authors the validity of doing serum PSA as a prostate cancer marker appears strongly questionable. Pre operative PSA value is less significant in predicting the biochemical failure or a significant predictor of biochemical recurrence also. Rather doing complexed PSA[ the acinar cells of prostate release PSA into blood where a proportion becomes bound to prostate inhibitors forming CPSA] is useful as total PSA level are indicative of NPH& C PSA rises predominantly in patients with malignant glands as per authors and data from European prostate cancer detection study also suggest that in patients with elevated PSA level(4--10ng/ml) C PSA is more accurate than total serum PSA.[The authors think DRE still can be considered as most important in mass screening and C PSA may be an additive in the prostate cancer screening, if DRE appears abnormal.] However the Positive predictive value of PSA may be increased when a researcher targets in a specific & ethnic population. It may be so that in some states of India or in some country, when biopsy were taken in men over 50 years age with a PSA value>2.5ng/ml, the prevalence of prostate cancer may be in some states or in some country increasingly or decreasingly variable. The PPV of PSA may be important when one considers patients age. However the role of PSA kinetics to the diagnosis of prostate cancer also remains controversial to authors. Proponents of PSA testing have to so accept the fact that it is far from perfect as up to 40% of detectable cancer in men with a normal PSA level(<4.0ng/ml). Though PSAD[ Prostate specific antigen density] may be much more important value then total PSA alone, yet PSAD also fails to diagnose 20% of significant prostate cancer[8]. PSAD has also its fallacies. Seaman [8] determined the normal PSAD for men with PSA level 4-10ng/ml to be<0.15. Using a PSAD threshold>0.12 and in that 16-55% reduction in biopsies could be done. The limitation of PSAD is that it involves the data based on TRUS. So newer one came, PSADTZ which is PSAD of transition zone of prostate. Only PSA velocity[PSAV] can improve the PSA specificity and may improve up to 44--96%and may be used in screening procedure Another question as a histopathologist the authors often face” has PSA any role to predict the developing risk of Prostate cancer?” When large group of men screened and biopsied for a greater value then 2.5ng/ml, the relative risk for developing prostate cancer was shown 5 times greater in men with a PSA value between 2ng/ml to 3ng/ml than in men with a PSA value less than 1ng/ml. Research shows 82% of cancer in younger men and 65% of cancer in older men would have been missed when we used traditional PSA threshold 4ng/ml[9]. Even 15% of cancer prostate with Gleason’s scoring 7 or greater have PSA value 3 ng/ml. f/t PSA using total PSA to diagnose prostate cancer patient with low PSA value can lead to diagnostic inaccuracy. In such cases f/t PSA can be used as indicator. In patients with a total PSA value 4--10ng/ml a f/t PSA value of <10% indicate 56% possibility. A f/t PSA value of <10% can also be used to distinguish Prostate cancer from BPH with PSA level 2,6-4 ng/ml PSA velocity (PSAV) is the absolute rate of change in PSA over time. An analysis [2005] of Baltimore longitudinal studies of aging cohort reported that a PSAV of >0.16 ng/ml/year identified men at considerable higher risk of death from prostate cancer[10] Two studies further indicate the use of PSAV as a screening test tool in men with a PSA level of < 4ng/ml using a PSAV threshold of 0.1ng/ml/year and with PSAV 85% of cancer can be correctly diagnosed [10,11], The role of preoperative PSAV in detecting subsequent risk of death from prostate cancer has been analyzed by D Amico et al with clinically localized prostate cancer & they reported that a pre operative PSAV of >2ng/ml/year was associated with lymph node metastasis and advanced pathological Gleason’s staging. This threshold level in PSAV was also associated with significantly shorter time to recurrence, death from prostate cancer [12] however Freedland et al told that preoperative PSAV do not predict biochemical recurrence or advance pathological features after radical prostectomy[12] So as per authors, pre operative PSAV appears to be most important predictors of death in patients with localized prostate cancer. Patients now have smaller volume of cancer with lower PSA level and lower stage of disease as our findings suggests. PSAV can be also used to stratify high risk patients who might benefit from adjuvant therapy from good risk patients who are likely to require standard therapy only. PSAV are also useful in monitoring disease recurrence also. References_: 1)Hsing. A.W, Kao.L, DevesaS.S” International trends and patterns of Prostate cancer incidence and mortality”- Int. J. Cancer 85;60-67;2000 2)Melia. Jane” The burden of prostate cancer, its natural history, information on outcome of screening and estimates of ad hoc screening with particular reference to England & Wales” -BJU Int. 95(suppl)4-15;2005 3)Stamely T.A, Freiha.F.S,, Mc.Neal JE etal “ Localized Prostate cancer relationship of tumor volume to clinical significance for treatment of prostate”- Cancer 71(supp-3);933-38;1993 4) Wilson SS;Crawford DE” Screening for prostate cancer current Recommendation” Urol cl. North .America 31;219-226;2004 5) Brawer MK” Prostate Specific antigen: current Status” Can. Cancer. J.Clin.49(5);264-81;1999 6) Heizsour. KJ, Newby.J; Comstock GW et al “prostate specific antigen level and subsequent prostate canmcer potential for screening “Cancer Epidemiology Biomarker Rev 1;537-40;1992 7) Stampy TA, Johnstone JM, Macneal JE etal “ Preoperative Serum prostate specific antigen levels between 2 and 22ng/ml correlate poorly with post radical prostate morphology: Prostate specific antigen cure rates appear constant between 2 and 9 ng/ml” J. Urol 167(1); 103-11;2002 8) Seaman E, Whang.M,,Olsson CA, Katz A etal “ PSA density(PSAD) role in patient evaluation and Management” Urol.clin.North America 20;653-63;1993 and Mettlin CL, Lithrup PG, Karner A etal “ Relative sensitivity & specificity of Serum prostate specific antigen(PSA) level compared with age referenced PSA, PSA density & PSA change- Data from American Cancer society National prostate cancer detection Project” Cancer 74;1615;1994 9) Reissigl.A, Pointer J, Horinger W etal “Comparison of different Prostate specific antigen cut off points for early detection of prostate cancer results of a large screening study” Urology 46;662-65;1995 10). Semus.J. Teachan, Laurance H. Klotz “current role of Prostate specific antigens in managing patients with prostate cancer”- BJU 97;451- 55;2005 Fang. J , Miller EJ,Landis P, Carter HB “ PSA velocity for assessing Prostate cancer risk in men with PSA level between 2.0 and 4.0 ng/ml- Urology 59;889-93;2002 11.) Roobol MJ, Kranase R, de Konning HJ, Schroder FH” Prostate specific antigen velocity at low prostate specific antigen level as screening tool for prostate cancer: results of second screening of ERPC. Urol 63;309-15;2004 12) D’Amico AV,Chen MH, Roehl AK Calalona NJ “ Preoperative PSA velocity and risk of death from prostate cancer after radical prostectomy” New. Eng,.J. Med 351;125-35;2004 and Freedland SJ, Dorey F, Aronsol WJ “ Preoperative PSA velocity and doubling time do not predict adverse pathologic features or biochemical recurrence after prostectomy” Urology 57;476-80;2001 Corresponding Author’s Address-:Professor Pranab Kr Bhattacharya Professor Dept. of pathology, In charge of Histopathology Unit, in charge of Cytogenetics, Ex-In charge of 24 hours Ronald Ross Malaria clinic, Technical Supervisor In charge of Blood Bank, 3rd floor, Dept. Of Pathology,Institute of Post Graduate Medical Education& Research (IPGMER) 244A AJC Bose Road, K0lkata-700020, India Email= profpkb@yahoo.co.in pranab@unipathos.com Competing interests: None declared |
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NAZAR R DESSOUKI, CONSULTANT SURGEON St. BERNARDS HOSPITAL GIBRALTAR
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With the widespread use of the prostate-specific antigen (PSA) test, smaller cancers are being detected among younger men and 5-year, cancer- specific, survival rates are on the rise. Although this lead-time effect may not translate into long-term improvement, these changes are a necessary prerequisite to effective screening. For high-risk patients, i.e., men with a family history of the disease and African American men, a strategy consisting of annual PSA blood testing and digital rectal examination for men ¡Ý40 years of age appears prudent. Many low/average- risk men of age 40 to 49 also request testing, and it is reasonable to offer testing and risk assessment to them. The exact screening threshold for total PSA levels for these men is not known, but 95% have PSA levels of ¡Ü1.5 to 2.5 ng/mL. PSA velocity (<20% per year), percentage of free PSA (>18¨C25%), and complexed PSA levels may be used to help determine risk. More study of young men is needed. Competing interests: None declared |
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