4. Methodology
4.2. Transformation Method Experimentation
4.3.2. Landmarking System Functionality
From literature review, prostatic neoplasia have been observed to show geographical, racial, and ethnic differences in their pattern of incidence, clinical presentations, and histological features. The treatment modalities also vary.
The objectives of this study, therefore, are to determine the following in respect of BPH and CaP in this locality:
i) Incidence ( including the age range, mean age, and peak age of occurrence);
ii) BPH:CaP ratio;
iii) Pattern of clinical presentation;
iv) Histological pattern; and v) Treatment modalities.
JUSTIFICATION FOR THE STUDY
This study is of great clinical significance in surgical practice. This is because prostatic neoplasia have been observed to constitute the bulk of the cases seen in any adult urologic practice5. They also afflict a very important age bracket of any population, with significant morbidity and mortality.
With increasing life expectancy, these diseases (BPH and CaP) which are strongly related to ageing, are assuming greater prominence globally, and therefore understandably continue to attract the attention of clinicians.
The well known geographical, racial, and ethnic variations in the pattern of prostatic neoplasia further justify the need for this study in this locality (Abakaliki-Ebonyi State), to compare results with existing statistics in other localities. There is currently no known existing published study on this subject in this locality.
SCOPE, INCLUSION AND EXCLUSION CRITERIA
The study was a one year prospective hospital-based study. All the adult male patients presenting to the Urology units during the study period, with LUTS suggestive of prostatic disease, were recruited.
However, only patients diagnosed of BPH or CaP after necessary evaluation qualified to be included for analysis. Those with inconclusive diagnostic evaluation, and therefore inconclusive diagnosis, were excluded from analysis. So were those that defaulted before final diagnosis.
AUTHOR’S ROLE
The author designed the proforma for the data collection, assessed the patients clinically, did 80% of the prostate biopsies, and actively participated in the peri-operative management and follow up of the patients.
LIMITATIONS
1. Low patient turn-out: This constraint was significantly overcome by using the two largest health institutions in the study locality as the study centres.
2. The low level of literacy among majority of the patients hindered ready extraction of some relevant information, especially demographic data, from such patients.
3. Transrectal prostate biopsy was digitally-guided due to non-availability of transrectal ultrasound probe for the more sensitive ultrasound guidance.
4. Financial constraints: In the absence of a research grant, a number of the patients recruited for the study could not afford the cost of the relevant investigations and were therefore excluded. Cost to the patient was also a major consideration in the choice of the treatment modalities.
MATERIALS AND METHODS
This study was prospective, hospital-based, and carried out at the Ebonyi State University Teaching Hospital and the Federal Medical Centre, both in Abakaliki, Ebonyi State, between October 2nd, 2007 and September 30th, 2008.
Subjects for the study were all the adult males presenting with lower urinary tract symptoms (LUTS) and diagnosed and managed as cases of benign prostatic hyperplasia (BPH) or carcinoma of the prostate (CaP) by the Urology units of the study centres during the study period.
The minimum sample size was calculated using the formula104,105: n = z2pq, where (based on the assumptions that):
d2
n = desired minimum sample size when the study population is >10,000
z = standard normal deviate = 1.96 (at 95% confidence level)
p = prevalence rate of prostatic neoplasia (unknown in this study locality and therefore assumed to be 50% = 0.5)
q = 1.0 – p
d = degree of accuracy desired (maximum tolerable or allowable sampling error) = 0.10
therefore, n = (1.96)2 (0.5) (0.5) = 3.84 x 0.5 x 0.5 = 0.96 = 96 (0.10)2 0.01 0.01
Approval was obtained from the Ethics and Research Committee. The patients, on presentation at the Urology clinics or Accident and Emergency departments, were evaluated clinically by detailed clerking and thorough physical examination ( see proforma ), after relieving any acute urinary retention present. By DRE, the prostate was assessed for size, consistency, nodularity, obliteration of the median groove, and mobility or fixity of the rectal mucosa. From the above, a working diagnosis of BPH or CaP was made. The following investigations were then carried out: full blood count, urinalysis with urine culture and sensitivity, serum electrolytes, urea, and creatinine (SEUCr), serum PSA assay, and abdomino-pelvic ultrasound (to assess the kidneys, ureters, bladder, and prostate). X-rays of the chest, spine/pelvis, as well as intravenous urogram, were done only where indicated. Indications for prostate biopsy included DRE findings suggestive of CaP, elevated serum PSA, and clinical or radiological evidence of metastasis from suspected CaP. Following informed consent, transrectal prostate biopsies were done using Tru-cut biopsy needles (size 16 or 18), under caudal block anaesthesia and
prophylactic antibiotics ( IV ciprofloxacin 400mg and metronidazole 500mg stat, given just before the anaesthesia ). The biopsies were digitally-guided in all cases since transrectal ultrasound probe for ultrasound guidance was not available at the study centres. The author did most (80%) of these biopsies while the consultants did the rest. The tissue specimens were preserved in formalin for histological examination by the pathologist who was one of the author’s supervisors. Surgical specimens from enucleated adenomas were similarly handled.
Patients in whom the final diagnoses were neither BPH nor CaP after clinical, biochemical, radiological, and histological investigations, were excluded from the study. Those who could not complete their diagnostic investigations, or who defaulted before definitive diagnosis, were also excluded. One of the patients with an intra-operative change in diagnosis was similarly excluded from analysis.
The choice of definitive treatment modality depended on the final diagnosis, availability and affordability of such a modality, patient’s fitness and preference, as well as the consultant surgeon’s preference and expertise. Patients with BPH were managed by watchful waiting, medical therapy using alpha-adrenergic blockers ± 5alpha-reductase inhibitor (finasteride), or surgery. After adequate preoperative work-up to optimize the patient’s condition, and having obtained an informed consent, surgery was by elective open prostatetctomy via the transvesical approach. Postoperatively, the patients had continuous bladder irrigation with Normal saline infusion for 24-48 hours. Skin
sutures were removed on the 7th day, and the urethral catheter on the 9th or 10th day before discharging the patient. Patients not fit or not ready for surgery were managed medically or with indwelling urethral or suprapubic catheter changed periodically (2-3weekly).
There were no functioning TURP facilities in the study centres during the period of the study.
All the patients with CaP presented with features of the late stages of the disease. They were therefore all managed palliatively by androgen deprivation therapy (ADT), using bilateral simple orchiectomy (BSO), alone or in combination with anti-androgens or stilbesterol. BSO was either total or subcapsular. One patient however had monotherapy using an anti-androgen alone. The variations in approach depended on the discretion of the consultant in-charge of each patient.
A proforma designed by the author was used to record the patients’
biodata, clinical presentations, results of investigations, final diagnosis, and treatment modalities. Data were analyzed using the Epi-Info statistical package, version10. Results were presented with the aid of tables and figures.
RESULTS
One hundred and sixty consecutive adult male patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) or carcinoma of the prostate (CaP) were recruited. Fifty patients were excluded due to inconclusive or intraoperative change in diagnosis. The remaining one hundred and ten patients with clinical and histological diagnosis of BPH or CaP were then analyzed. Analysis was with respect to the final diagnosis, BPH:CaP ratio, incidence, age distribution, duration and prevalence of symptoms, prostate enlargement on digital rectal examination and ultrasound scan, PSA values, histological reports, and treatment modalities used.
FINAL DIAGNOSIS
Eighty five (77.3%) of the patients had BPH while twenty five (22.7%) had CaP, giving a BPH:CaP ratio of 3.4:1, and incidence rates of 212/100,000 for BPH, and 62/100,000 for CaP (Table 1). The incidence rates were determined based on the hospital attendance of
40,000 males aged above 40 years during the period of the study. The CaP incidence rate was compared with those reported in Portharcourt and Lagos, and the observed differences subjected to a test of statistical significance, using the test of proportion, at 95% confidence interval, and interpreted at P=0.05 as significnt.
TABLE 1. DISTRIBUTION OF THE FINAL DIAGNOSES OF PROSTATIC NEOPLASIA
Diagnosis Frequency Percentage (%) BPH 85 77.3
Ca Prostate 25 22.7 Total 110 100.0
AGE DISTRIBUTION
The patients with BPH were aged 42–80 years, with a mean of 65.61 ± 7.79 years, while the patients with CaP were aged 47–85 years, with a mean of 65.93 ± 9.95 years.
The peak age of occurrence was in the 7th decade for BPH and 6th decade for CaP . Figure 2.
FIGURE 2. GRAPH OF THE AGE DISTRIBUTION OF BPH AND CaP, SHOWING THE PEAK AGES OF OCCURRENCE
40
30
DURATION OF SYMPTOMS AT PRESENTATION
All the patients presented with lower urinary tract symptoms of varying durations. Of the patients with BPH, 43.5% (n=37) presented within 6 months of onset of symptoms, while 56.5% (n=48) presented after 6 months. 40.0% (n=10) of the patients with CaP presented within 6 months while 60.0% (n=15) presented after 6 months of onset of symptoms .Table 2.
TABLE 2: DURATION OF SYMPTOMS AT PRESENTATION IN BPH AND CARCINOMA OF THE PROSTATE
Duration of BPH CaP Total
Symptoms (months)
<1 13 (15.3%) 3 (12.0%) 16 (14.6%)
1 – 6 24 (28.2%) 7 (28.0%) 31 (28.2%) 7 – 12 21 (24.7%) 4 (16.0%) 25 (22.7%)
>12 27 (31.8%) 11 (44.0%) 38 (34.5%) Total 85 (100%) 25 (100%) 110 (100%)
PREVALENCE OF SYMPTOMS Frequency
The commonest irritative symptoms in patients with BPH were frequency (84.7%, n=72), urgency (63.5%, n=54), and nocturia (60.0%, n=51). The commonest obstructive symptoms were poor urinary stream (63.5%, n=54), terminal dribbling (44.7%, n=38), and feeling of incomplete voiding (43.5%, n=37). 52.9% (n=45) of the patients had urinary retention (acute in 50.6%, n=43; and chronic in 2.3%, n=2).
In patients with CaP, frequency was also the commonest irritative symptom (84.0%, n=20), followed by nocturia (64.0%, n=16) and urgency (60.0%, n=15). The most frequent obstructive symptoms were terminal dribbling (60.0%, n=15), poor urinary stream (52.0%, n=13), and feeling of incomplete voiding (40.0%, n=10). Urinary retention occurred in 72.0% (n=18) of the patients, with 64.0% (n=16) being acute and 8.0% (n=2) being chronic.
21.2% (n=18) of the patients with BPH, and 16.0% (n 4) of those with CaP presented with macroscopic haematuria. The haematuria was gross and persistent in three of the patients with BPH, necessitating emergency open (transvesical) prostatectomy .Table 3.
TABLE 3. PREVALENCE OF SYMPTOMS IN BPH AND CaP Symptom BPH CaP Total
Frequency 84.7%(n=72) 84.0%(n=21) 84.5%(n=93) Urgency 63.5%(n=54) 60.0%(n=15) 62.7%(n=69) Nocturia 60.0%(n=51) 64.0%(n=16) 60.9%(n=67) Urge incontinence 36.5%(n=31) 40.0%(n=10) 37.3%(n=41) Hesitancy 41.2%(n=35) 32.o%(n=8) 39.1%(n=43) Poor urinary stream 63.5%(n=54) 52.0%(n=13) 60.9%(n=67) Terminal dribbling 44.7%(n=38) 60.0%(n=15) 48.2%(n=53) Feeling of incomplete
voiding 43.5%(n=37) 40.0%(n=10) 42.7%(n=47)
Urinary Retention 52.9%(n=45) 72.0%(n=18) 69.3%(n=63) Acute 50.6%(n=43) 64.0%(n=16) 64.9%(n=59) Chronic 2.3%(n=2) 8.0%(n=2) 4.4%(n=4) Straining 40.0%(n=34) 16.0%(n=4) 34.5%(n=38) Intermittency 29.4%(n=25) 20.0%(n=5) 27.3%(n=30) Haematuria 21.2%(n=18) 16.0%(n=4) 20.0%(n=22)
Others
Low back pain 15.3%(n=13) 40.0%(n=10) 20.9%(n=23) Fractures(prox. femur)- 8.0%(n=2) 1.8%(n=2) Weight loss 4.7%(n=4) 24.0%(n=6) 9.1%(n=10) Neurological deficits - 8.0%(n=2) 1.8%(n=2)
TABLE 4. SEVERITY OF SYMPTOMS (IPSS) IN BPH PATIENTS AT PRESENTATION
SEVERITY FREQUENCY Mild (0–7) 5 (5.9%)
Moderate (8–19) 23 (27.0%) Severe (20-35) 57 (67.1%) Total 100% (n=85)
NOTE: IPSS = International Prostate Symptom Score
PROSTATE VOLUME ON ULTRASOUND SCAN
The prostate volume in patients with BPH ranged from 26.0cm3– 159.2cm3, with a mean of 76.3 ± 31.9cm3. 35.3% (n=30) measured ≤ 60cm3 while the rest (63.7%, n=55) measured >60cm3. Table 5.
TABLE 5. PROSTATE SIZE (VOLUME) ON ULTRASOUND SCAN Prostate Volume
(cm3) Frequency
21-40 9.4% (n=8)
41–60 25.9% (n=22) 61- 80 29.4% (n=25)
81 –100 14.1% (n=12) 101-120 8.2% (n=7)
121 –140 7.1% (n=6) 141 –160 5.9% (n=5)
Total 100% (n=85)
PSA VALUES
The total serum PSA in patients with BPH ranged from 0–87ng/ml, with a mean of 15.77 ± 20.08ng/ml. It was 0–4ng/ml in 41.2% (n=35), 5–10ng/ml in 16.5% (n=14), 11–20ng/ml in 17.6% (n=15), and
>20ng/ml in the rest of the patients (24.7%, n=21).
In the patients with CaP, the PSA values ranged from 0.6–100ng/ml, with a mean of 38.82 ± 27.14ng/ml. It was 0-4ng/ml in 4.0% (n=1), 5–
10ng/ml in 8.0% (n=2), 11–20ng/ml in 20.0% (n=5), and progressively
>20ng/ml in the rest of the patients (68.0%, n=17). Table 6.
TABLE 6. SERUM PSA VALUES IN BPH AND CaP
Serum PSA (ng/ml) BPH CaP Total
0 – 4 41.2%(n=35) 4.0%(n=1) 32.7%(n=36) 5 – 10 16.5%(n=14) 8.0%(n=2) 14.6%(n=16) 11 – 20 17.6%(n=15) 20.0%(n=5) 18.2%(n=20)
>20 24.7%(n=21) 68.0%(n=17) 34.5%(n=38) Total 100.0%(n=85) 100.0%(n=25) 100.0%(n=110)
UPPER URINARY TRACT DILATATION (ON USS)
In the patients with BPH, dilatation of the upper urinary tracts was present in 11.8% (n=10) and absent in 88.2% (n=75). In patients with CaP, it was found in 28.0% (n=7) but absent in 72.0% (n=18).
RENAL FUNCTION DERANGEMENT
The renal functional status, as assessed by the serum urea and creatinine levels, was deranged in 15.3% (n=13) of the patients with BPH, and in 32.0% (n=8) of those with CaP.
HISTOLOGY REPORTS
Prostate biopsy was indicated and performed in 63.6% (n=70) of the 110 patients after clinical and biochemical evaluation. Forty-five of those biopsied were histologically BPH while twenty-five were CaP. Of the patients with histological BPH, 22.2% (n=10) had co-existing chronic prostatitis. All the cases of CaP were adenocarcinoma, with Gleason’s score of 2–4 in 28.0% (n=7), 5-7 in 40.0% (n=10), and 8-10 in the remaining 32.0% (n=8) patients. Table 7.
TABLE 7. HISTOLOGICAL PATTERN OF PROSTATIC NEOPLASIA
Histology Report Frequency
BPH 40.9% (n=45)
With chronic prostatitis 22.2% (n=10) Without chronic prostatitis 77.8% (n=35)
CaP 22.7% (N=25)
Adenocarcinoma 100% (n=25) GS 2-4 28.0% (n=7) GS 5-7 40.0% (n=10) GS 8-10 32.0% (N=8) Total 63.6% (n=70) 100.0%(n=45) 100.0% (n=25)
Note : GS = Gleason’s score.
TREATMENT MODALITIES
5.9% (n=5) of the patients with BPH had mild LUTS (IPSS=0-7) and were managed by watchful waiting. Medical therapy with 1-adrenergic blockers ± -reductase inhibitor (finasteride) was the treatment modality in 27.0% (n=23) of the cases. Although prostatectomy was indicated in 67.1% (n=57) of the cases, only 31.8% (n=27) of these had the surgery (TVP) during the period of this study, while 35.3% (n=30) were on catheter drainage (urethral or suprapubic) awaiting surgery (Table 8). Three of the patients had emergency prostatectomy due to severe and persistently bleeding BPH.
84.0% (n=21) of the patients with CaP had bilateral orchiectomy (BSO). Bilateral orchiectomy was the only form of hormone (androgen) deprivation therapy in 60.0% (n=15) of the patients, but was combined with an anti-androgen (bicalutamide) in 8.0% (n=2), and with low dose
stilbesterol in 16.0% (n=4) of the patients. An anti-androgen (bicalutamide) was the only form of therapy in 4.0% (n=1) of the patients. Three (12.0%) of the patients absconded before any form of definitive treatment could be instituted after diagnosis. Table 9.
TABLE 8. TREATMENT MODALITIES FOR BPH
Treatment Modality No. of Cases Percentage(%)
Watchful waiting 5 5.9
1–blockers ± finasteride) 23 27.0
Transvesical prostatectomy 27 31.8
Catheter drainage 30 35.3
(awaiting surgery)
Total 85 100.0
TABLE 9. TREATMENT MODALITIES FOR CaP
Treatment Modality No. of cases Percentage(%) Bilateral orchiectomy 21 84.0
Alone 15 60.0
Plus stilbesterol 4 16.0
Plus anti-androgen 2 8.0
Anti-androgen alone 1 4.0
Defaulters (after diagnosis) 3 12.0
Total 25 100.0