To study postorchiectomy anaemia in black Nigerian patients who had bilateral orchiectomy for advanced carcinoma of the prostate. Anaemia has been observed in similar studies done on Caucasians and non-black patients in non-tropical environments : Consecutive patients with advanced carcinoma of the prostate who were managed by the authors over a four-year period, and who were treated with bilateral orchiectomy were prospectively studied.They also satisfied the set criteria for inclusion in the study.Thirty-six patients were studied. The mean age was 71 years (SD=7.6). Preoperative white blood cell count with blood film examination, and serum urea and creatinine were within normal limits and remained so for the duration of the study. The mean value of the haemoglobin concentration dropped significantly from 11.9g/dl to 10.1g/dl at sixmonths (p Keywords: Post-Orchiectomy Anaemia; Advanced Carcinoma of Prostate  Nigerian Journal of Clinical Practice Vol. 11 (1) 2008: pp. 1-

Chukwujama, NO

Egbunam, BE

Orakwe, JC

English

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INTRODUCTIONBilateral orchiectomy is a major therapeutic optionin the management of patients with advancedcarcinoma of the prostate and in our environmentand centres, it is the main modality available . Thecurrent therapeutic strategy of newly diagnosedprostate cancer is however dependent on the stage ofthe disease. While most organ-confined diseases aresubjected to radical prostatectomy or brachytherapy,the choice for advanced carcinoma of the prostate isbased on androgen manipulation .The effects of androgen on haematopoiesis havebeen studied extensively, and normocytic,normochromic anaemia has been found to beassociated with androgen deprivation . Variousstudies have also shown that haemoglobin levelsdeclined in parallel with serum testosterone fromnormal levels, rising again on return of the serumtestosterone to normal values. No associatedchanges were found in the levels of serumerythropoeitin . In our practice, we observed thatCorrespondence: Dr J C Orakwe12, 32, 4,52, 5, 6E-MAIL: jayceeorakwe @ yahoo.comanaemia developed in our patients after bilateralorchiectomy for advanced carcinoma of the prostate,such anaemia sometimes being of sufficient severityto warrant blood transfusions. We also noted from theavailable literature that studies have been done on theanaemia associated with bilateral orchiectomy .These studies were done on Caucasians and non-black races. Based on these earlier observations inother environments, clinical settings and racialgroups, we decided to study systematically ourpatients with carcinoma of the prostate who weretreated with bilateral orchiectomy. This is a report ofthe observations made on the anaemia associatedwith bilateral orchiectomy for advanced carcinoma ofthe prostate in tropical sub-SaharanAfrica.All patients who presented to the authors withadvanced carcinoma of the prostate and were treatedwith bilateral orchiectomy were studied. The patientspresented between July 1, 2000 and June 30, 2004 atthe Nnamdi Azikiwe University Teaching Hospital,Nnewi, Nigeria, and the Macbenson Hospital,4,5MATERIALSAND METHODSNigerian Journal of Clinical PracticeMarch 2008 Vol 11(1):1-4POST-ORCHIECTOMY ANAEMIA IN PATIENTS WITH ADVANCEDCARCINOMA OF THE PROSTATEJ.C Orakwe , N.O Chukwujama , B.E .EgbunamABSTRACTObjective:Materials And MethodsResultConclusion.Keywords:Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, NnewiAccepted 27 February 2007)To study postorchiectomy anaemia in black Nigerian patients who had bilateral orchiectomy foradvanced carcinoma of the prostate. Anaemia has been observed in similar studies done on Caucasians andnon-black patients in non-tropical environments: Consecutive patients with advanced carcinoma of the prostate who were managedby the authors over a four-year period, and who were treated with bilateral orchiectomy were prospectivelystudied. They also satisfied the set criteria for inclusion in the study.: Thirty-six patients were studied. The mean age was 71 years (SD=7.6). Preoperative white blood cellcount with blood film examination, and serum urea and creatinine were within normal limits and remained sofor the duration of the study. The mean value of the haemoglobin concentration dropped significantly from11.9g/dl to 10.1g/dl at six months (p<0.005). The prostate specific antigen decreased from a mean preoperativevalue of 62.2ng/ml (SD=58.6) to a mean postoperative nadir of 2.9ng/ml (SD=1.3) after three months.: In Nigerians, there is a statistically significant decrease in the heamoglobin concentration afterbilateral orchiectomy This should be closely monitored, and treated when indicated.Post-Orchiectomy Anaemia; Advanced Carcinoma of Prostate (1Onitsha, Nigeria. They were all of the Black Africanrace. Criteria for inclusion in the study were asfollows: -1. Histologically proven carcinoma of theprostate2. Normal pre-operative (baseline) haemoglobinconcentration and white blood cell countincluding blood film.3. Normal pre-operative renal function that alsoremained normal for the duration of the study.4. Adequate post-operative follow up period of atleast six months5. Evidence of complete response to orchiectomywith no evidence of disease progression duringthe period of study6. Absence of radiological evidence of skeletalmetastasis7. Absence of any other explanation for theanaemia e.g haematological disorders.Thus, the baseline evaluation included a full bloodcount with a blood film examination, serum urea andcreatinine, serum prostate specific antigen, chest x-ray, and x-ray of the lumbo-sacral spine and pelvis.For the purpose of this study, the evaluation of thefull blood count was repeated postoperatively everymonth for three months, and then at six months.Serum urea and creatinine and serum PSA wererepeated at least once within the duration of thestudy, usually between the third and the sixth month.Haemoglobin concentrations were estimatedmonthly within the preceding 3-6 months beforeoperation. If it was found that the haemoglobinconcentration had decreased through one or twosucceeding assessments during the period, thepatient was excluded from further evaluation for thepurpose of this study.Haemoglobin concentration2value below which anaemia is suggested for theordinary Nigerians is 11gm/dl and this value wasapplied in this study. Statistical analysis was doneusing simple descriptive statistics and the unpairedstudents 't'-test. Fisher's F-test of differences ofvariance was always applied before the use of the t-test, and the z-test used if it was significant. Acceptedlevel of significance was p<0.05.Forty-four patients presented during the period, 34 ofthem at the Nnamdi Azikiwe University TeachingHospital, and 10 at MacBenson Hospital. Of theseonly 36 patients satisfied the set criteria and werestudied. The mean age of the patients studied was71.1 (SD=7.6) years, with a median of 71years, and arange of 56-83 years.The clinical stage of the prostatec a n c e r i n c l u d e d 2 0 p a t i e n t s w i t h T 3(Stage C) and 16 patients with T4 (Stage D). Therewas no evidence of disease progression during theperiod of study.Pre-operative values of the white blood cell count,serum urea and creatinine (Table I) were within thenormal limits of 4 11000/mm , 2-6mmol/litre, and60-120umol/litre respectively, and they remainedwithin these normal limits for the duration of thestudy. Blood film studies were normal. The meanprostate specific antigen value decreased from 62.2(SD=58.6) ng/ml preoperatively to a mean nadir of2.9(SD=1.3) ng/ml after 3 months. The preoperativerange of values was 10.2-226ng/ml with a median of50ng/ml, and the postoperative range was 1.4-6.7ng/ml with a median of 2.7ng/ml.Table II shows the postorchiectomy haemoglobinconcentrations. From a mean preoperative value of73RESULTTable 1oPSA = Prostate SpecificAntigen, WBC = White Blood Cell Count, Prp = Preoperative,mt = Month> = More than: Preoperative White Blood Cell Count, Urea, Creatinine, And PSA Levels In 36 Patients WithAdvanced Carcinoma fThe Prostate.WBC UREAESTIMATIONS ng/ml mmPrpPSA CREATININE>3 mmol/l μmol3mt Prp >3mt Prp >3mt Prp >3mtMEAN VALUE 62.18 2.93 6410 6320 4.81 4.60 102.33 98.4STANDARD DEVIATION 54.58 1.26 2190 1820 0.92 0.83 13.51 9.8MEDIAN 50.00 2.70 5800 6100 4.95 4.72 107 103.2RANGE 10.20 1.40 4100- 4200 3.3 2.6 55 7 3-226 -6.70 10800 -10600 - 6.2 -5.3 118 -110KEY:Nigerian Journal of Clinical Practice March . 2008, Vol.11(1) Post- Orchiectomy Anaemia Orakwe et alHowever, in 21(58.3%) patients, the haemoglobinconcentration fell below 11.0gm/dl at some pointduring the postorchiectomy period. In 4 patients,either because of the severity of the anaemia alone(<7g/dl) or because of the development of anaemicsymptoms (fatigue, dyspnoea, dizziness, loss ofappetite inability to concentrate), blood transfusionshad to be given during the later course of the study. Inall our studied patients, the levels of the haemoglobinconcentrations estimated at monthly intervalspreoperatively were either stable, or were improvedunder our pre-operative care.11.9g/dl, the concentration fell to 11.3g/dl at 1month, 10.9g/dl at 2 months, 10.6g/dl at 3 monthsand 10.1g/dl at 6 months. The preoperative meanhaemoglobin concentration was compared with theunder our pre-operative care.postoperative values asshown in Table III.The preoperative value of the haemoglobinconcentration was statistically significantly differentfrom the mean values at each month of evaluation(P<0.005). The mean drop of haemoglobin from thebaseline to the end of the study at six monthspostoperatively was 1.8g/dl.3Table IITable III:: Postorchiectomy Haemoglobin ConcentrationsMONTHS NO OF MEAN HB STANDARD MEDIAN RANGEPOST-OP PATIENTS (g/d1) DEVIATIONO(Pre-op) 36 11.9 1.3 11.7 11.1-14.71 36 11.3 1.1 11.3 9-13.72 36 10.9 1.2 10.9 7.6-13.73 34 10.6 1.1 10.7 7.9-13.26 32 10.1 0.9 10.6 9.2-12.6Comparison of PreoperativeAnd Postoperative Haemoglobin ConcentrationsCOMPARED GROUPS MEAN DIFFERENCE “t” p valueIN HB CONC.(g/d1) (P<0.05)Preoperative vs .1 month 0.6 2.17 <0.005stPreoperative vs .2 month 1.0 3.32 <0.0005Preoperative vs .3 month 1.3 4.85 <0.0005Preoperative vs .6 month 1.8 4.07 <0.0005ndrdrdthat there was response to the orchiectomy with noevidence of disease progression during the period ofstudy. In all the cases, the PSA dropped to a nadir bythree months and remained so during the period of thestudy. Renal failure that could be a source of anaemiain such urological patients was excluded in all thepatients by the estimation of the serum urea andcreatinine levels. We tried to exclude anaemia ofchronic diseases and other factors that may cause acoincidental drop in haemoglobin concentration byensuring a normal preoperative haemoglobinconcentration and also proposing exclusion forpatients whose monthly preoperative haemoglobinconcentrations were observed to have had a declinewhatever the cause. However, none of our patientswas so excluded.Our study provides no pathophysiologicalexplanation for the decrease in haemoglobinDISCUSSIONThis study indicates that in our environment, andprobably in the Black (Negro) race too, there is astatistically significant decrease in haemoglobinconcentration in the patients after bilateralorchiectomy for advanced carcinoma of the prostate.In our centres, bilateral orchiectomy is the mainmodality available for the treatment of advancedcarcinoma of the prostate.Potential confounding factors for anaemia inadvanced carcinoma of the prostate include bonemarrow involvement and the anaemia caused by theburden of chronic diseases. It is to limit theseconfounders that the patients with evidence ofskeletal metastasis were excluded within thefacilities available to us. We also ensured that theperipheral blood films were not suggestive of anybone marrow depressing or replacing process, andNigerian Journal of Clinical Practice March . 2008, Vol.11(1) Post- Orchiectomy Anaemia Orakwe et alconcentration but we believe, as has been shown byother studies, that it was due to the androgendeprivation from the bilateral orchiectomy . Suchanaemia is usually normocytic and normochromicand this was our finding in this study. Similarnormocytic and normochromic anaemia have alsobeen demonstrated using monotherapy with LHRHanalogues, which achieve similar mode of androgendeprivation as bilateral orchiectomy. Anaemia hashowever not been found in patients treated withantiandrogen monotherapy, which has a differentmode of androgen deprivation .Though we have not evaluated the treatment of suchorchiectomy-induced anaemia in our study, wehowever ensured that before and during the study, allthe patients were on iron supplementation therapy.This was to ensure adequate iron stores in thepatients, a habit we had developed earlier in our pre-study postorchiectomy patients on observinganaemia in them.The anaemia observed in the patients with advancedcarcinoma of the prostate after bilateral orchiectomyin our environment is real and similar to thatobserved in other races and environments. We advisethat patients who have had bilateral orchiectomyshould be closely monitored for anaemia. Prompttreatment should be initiated in the patients whodevelop severe or symptomatic anaemia because ofthe effects of anaemia on the quality of lifeOccurrence of postorchiectomyhot flushes in Nigerians: a preliminary report.Nig. J. Surg Res. 2001; 3(2); 56-61Combined androgen blockade-inducedanaemia in prostate cancer patients withoutbone involvement. Anticancer Research, 2003;23; 1757-1762.How is androgen-dependent metastatic cancer best treated.Haematol Oncol Clin N.Am, 1996; 10: 727.Anaemia after orchiectomy.Am J. Haematol, 1998; 59: 230-233.2, 4,510CONCLUSIONREFERENCES1. Orakwe JC.2 Bogdanos J, Kammanolakis D, ConstantineM, Repousis P, Tsintavis A, Koutsilieris M.3. Robson M, Dawson M.4. Fonseca R, Rajkumar SV, White WL, TefferiA, Hoagland HC.5 Strum SB, McDermed JE, Sholz MC,Johnson H, Tisman G.6. Weber JP, Walsh PC, Peters CA, Spivac JL.7 Watson RS, Etta KM.8 Geller J, Albert J, Vik A.9. Eri LM, Tveter KJ.10. Decensi A, Torrisi R, Fontana V.Anaemia associatedwith androgen deprivation in patients withprostate cancer receiving combined hormoneblockade. Brit J Urol, 1997; 79: 933-941.Effect of reversible androgen deprivation onhaemoglobin and serum immunoreactiveerythropoietin in men. Am. J Hematol, 1991,36: 190.Some blood indices inthree groups of Nigerians and in very severe butambulatory cases of anaemia. J Trop Med Hyg.1975; 78(1): 13-18advantages of totalandrogen blockade in treatment of advancedprostate cancer. Semin Oncol. (Suppl. I), 1998;15: 53.Safety, side effects andpatient's acceptance of the luteinising hormonerelease agonist Leuprolide in the treatment ofbenign prostatic hyperplasia. J. Urol, 1994; 152:448-452.Stimulationof erythropoiesis by the non-steroidal anti-androgen nilutamide in men with prostatecancer. Evidence for an agonist effect. Br. JCancer, 1994; 69: 617-619.4Nigerian Journal of Clinical Practice March . 2008, Vol.11(1) Post- Orchiectomy Anaemia Orakwe et al

Post-Orchiectomyanaemia in patients with advanced carcinoma of the prostate

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Post-Orchiectomyanaemia in patients with advanced carcinoma of the prostate

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