• No results found

patients with hard or nodular prostates and 45 patients with serum PSA of 10ng/ml to 134ng/ml had prostate biopsy and of these 26

The mean PSA for patients treated with 0.5mg dutasteride was 22.9ng/ml while the mean PSA for those who had normal saline irrigation only was 29.3ng/ml and this was not statistically different (t- test = -0.903, p=0.370).

Pearson correlation was done to test the relationship between level of PSA and duration of haematuria while using dutasteride. The result

showed a negative correlation which was not statistically significant (N=36, r

= -0.060, p- value = 0.730).

All 19 patients with hard or nodular prostates and 45 patients with

Table 6: Diagnosis and type of treatment

Treatment

Diagnosis Normal Saline and Normal Saline Total Dutasteride Irrigation only

BPH 24 (49.0) 25 (51.0) 49

CaP 12 (46.2) 14 (53.8) 26 Total 36 (48.0) 39 (52.0) 75

Heamaturia stopped in all 24(100%) patients with BPH on the dustateride group and in 24 (96%) of the 25 patients on the normal saline control group.

The remaining 1(4%) patient had open prostatectomy and haematuria subsequently stopped. Also, haematuria stopped in all of the 12 (100%) patients with CaP who were on the dutasteride arm but on 12 (85.7%) of the 14 patients on the normal saline control arm. The 2 (14.3%) CaP patients

whose haematuria did not resolve had bilateral subcapsular orchidectomy and haematuria resolved subsequently.

In all, haematuria resolved in 36 patients who had dutasteride but in 36(92.3%) of the 39 patients on the normal saline control arm. Three (7.7%) of 39 patients on the normal saline control arm needed surgery (orchidectomy or prostatectomy depending on the diagnosis) to stop haematuria.

In patients with BPH on the control arm, haematuria lasted between 3 days and 38 days with a mean duration of 8.0 ± 6.8 days and between 2 days and 15 days with a mean duration of 4.9 ± 2.9 days in those treated with dutasteride (table 7). Kaplan Meier Survival Analysis procedure was used to examine the distribution of time it took haematuria to stop for the two different types of treatment. The comparison tests show that there was a statistically significant difference between them (fig. 3 ).

Table 7: The minimum and maximum duration (in days) of haematuria and mean duration (in days) of haematuria for each diagnosis and for each treatment type.

Diagnosis N Means±SD Minimum Maximum

Normal

Saline and 24 4.9 ± 2.9 2 15 Dutasteride

Benign

Prostatic Normal Saline

Hyperplasia Irrigation only 25 8.0 ± 6.8 3 38

Normal Saline

and Dutasteride 12 4.7 ± 1.9 1 8 Cancer of

Prostate

Normal Saline

Irrigation only 14 6.9 ± 2.3 3 10

Figure 3: Kaplan Meier analysis for duration of haematuria for the two arms of treatment.

The horizontal axis shows the time to effect (time of resolution of

haematuria). The vertical axis shows the probability of survival (probability of resolution of haematuria). Thus, any point on the survival curve shows the probability that a patient on a given treatment will have experienced relief at that time.

The plot for Normal Saline and dutasteride was below that of Normal Saline irrigation only (shorter time) throughout most of the trial, which suggests that normal saline and dutasteride may give a faster relief than normal saline irrigation only.

To determine whether the differences were due to chance, the means and medians for the survival time/ time to resolution of haematuria were

compared for the two treatment arms and this showed significant difference in the average time in favour of the dutasteride group(p= 0.009)( table 8 and table 10)

Table 8: Means and Medians for Survival Time Treatment

Mean Median

Estimate Std. Error 95% Confidence Interval

Estimate Std.

Error

95% Confidence Interval Lower

Bound

Upper Bound

Lower Bound

Upper Bound Normal Saline and

Dutasteride 6.492 0.819 4.885 8.098 5.000 0.458 4.102 5.898

Normal Saline Irrigation only 11.039 2.512 6.116 15.962 8.000 0.596 6.832 9.168

Overall 8.779 1.390 6.055 11.503 7.000 0.628 5.770 8.230

Table 9: Percentiles Table for the Survival Curve ( Probability of Resolution of Haematuria )

Treatment 25.0% 50.0% 75.0%

Estimate Std. Error Estimate Std. Error Estimate Std. Error

Normal Saline and Dutasteride 9.000 2.043 5.000 0.458 4.000 0.313

Normal Saline Irrigation only 11.000 2.521 8.000 0.596 6.000 0.770

Overall 11.000 1.044 7.000 0.628 4.000 0.398

The percentile table for the survival curve for the two arms of treatment was also compared and it showed significant difference in favour of the group treated with dutasteride. For instance, the 75th percentile is the time at which 75% of the patients are yet to have their haematuria resolved. For the group treated with dutasteride, this was at 4 days. At 50th percentile, 50% of patients still have symptoms and this corresponded to 5 Days. Similarly, 25%

of patients had symptoms at 25 percentile, corresponding to 9 days. The values for those treated with normal saline irrigation only were 6days, 8 days, and 11 days corresponding to 75, 50, and 25 percentiles respectively ( Table 9 ).

Table 10: Overall Comparisons of Log Rank, Wilcoxon, and Tarone Wares tests in relation to time to resolution of haematuria.

X2 df p-value

Log Rank 6.779 1 0.009

Breslow ( Generalized Wilcoxon)

10.207 1 0.001

Tarone-Ware 8.944 1 0.003

Table 10 provides overall tests of the equality of survival times (probability of resolution of haematuria) across groups. Since the significant values of the tests are all less than 0.05, it means there is a significant difference in the

survival curves.

BPH patients on the normal saline control arm required between 6 litres

and 55 litres of irrigation fluid with a mean volume of 21.0 ± 11.9 litres to stop haematuria while those that had 0.5mg dutasteride in addition required between 4 litres and 20 litres with a mean volume of 10.4 ± 5.2 litres before haematuria stopped. A two sample student t-test was used to test whether the volume of irrigant fluid used for the two groups were different. This was statistically significant in favour of those who received dutasteride (t= -2.885, p=0.008) (table 11).

The CaP patients on the control arm required between 4 litres and 48 litres of irrigation fluid with a mean volume of 17.4 ± 9.7 litres before haematuria stopped while those on the dutasteride arm required between 3 litres and 20 litres with a mean volume of 8.3 ± 4.6 litres. A two sample student t- test was used to test if the mean volume of irrigation fluid for the two groups were different. It was statistically significant in favour of those who used dutasteride ( t= -4.115, p= 0.000) (table 11).

Table 11: Cross tabulation of diagnosis and treatment showing mean volume of irrigation fluid used before haematuria stopped and two sample student t- test and p value.

Normal Saline Normal Saline

Diagnosis and Dutasteride Irrigation only t-test P-value Mean±SD Mean±SD

BPH 10.3±5.2 21.0±119 -2.885 0.008 CaP 8.3±4.6 17.4±9.7 -4.155 0.000

One (4%) of 25 BPH patients on normal saline control arm required emergency prostatectomy to stop bleeding while none of the 24 BPH patients on the dutasteride arm had prostatectomy. Fisher’s Exact was used to test if inclusion of dutasteride reduced need for prostatectomy and it was not significant (Fisher’s Exact; p=0.140) (table 12).

Similarly, 2(14.2%) of the CaP patients on the normal saline arm needed orchidectomy to stop bleeding while none of the 12 patients on the

dutasteride arm had orchidectomy. Fisher’s Exact was used to test if inclusion of dutasteride reduced need for orchidectomy to stop haematuria and it was not significant (Fisher’s Exact:p=0.280). In all, 3(7.7%) of 39 patients on the control arm had surgery (either prostatectomy or bilateral orchidectomy,

depending on the diagnosis) to stop haematuria while none of the 36 patients that took dutasteride had surgery. (Fisher’s exact test: p=0.420) (Table 12).

Table 12: Fisher’s Exact Test for need for surgery when dutasteride is included

Treatment

Diagnosis Normal Saline and Normal Saline P-Value Dutasteride Irrigation only

Surgery Surgery Yes No Yes No

BPH 0 24(100) 1(4.0) 24(96.0) 0.140

CaP 0 12(100.0) 2(14.3) 12(85.7) 0.280 TOTAL 0 26(100) 3(7.7) 36(92.3) 0.420

Fisher’s Exact Test was used for the statistics

A total of 7(9.3%) of the patients were transfused after initial stabilization at haemoglobin 10g/dl. Three of the patients had BPH. One (33.3%) of them received 0.5mg dutasteride while 2 (66.7%) were on the control arm. Fisher’s exact test was performed to test if there was a significant influence of

inclusion of dutasteride to reduce need for blood transfusion. The result showed that there was no significant influence (Fisher’s exact test = 0.516) (table 13). The remaining 4 patients had CaP. Two (50%) were on each side of the treatment. Fisher’s exact test was performed to test if there was a significant influence of the inclusion of dutasteride to reduce need for blood transfusion. The result showed that there was no significant influence (Fisher’s exact test =0.641) (table 13).

Table 13: Requirement for blood transfusion

Diagnosis

BLOOD TRANSFUSION

Fishers Exact Test Normal Saline

and Dutasteride

Normal Saline Irrigation only

No Yes No Yes

BPH 23 (95.8) 1 (4.2) 23 (92.0) 2 (8.0) 0.516

CaP 10 (83.3) 2 (16.7) 12 (85. 7) 2 (14.3) 0.641

Total 33 3 35 4

Fisher's Exact Test was used for test of significance where the samples are too small to use X2

Fifteen (60%) of 25 BPH patients on the control arm had recurrent haematuria after initial resolution while 4(16.7%) of 24 BPH patients on the dutasteride arm had recurrent haematuria. A chi-square test was used to test if inclusion of dutasteride reduced incidence of recurrent haematuria and it was found statistically significant (X2 = 9.685, p=0.003). Similarly, 7 (50.0%) of 14 CaP patients on the control arm had recurrent haematuria while 1 (8.3%) of 12 CaP patients who received dutasteride had recurrent haematuria. A chi-square test was used to test if inclusion of dutasteride reduced incidence of recurrent haematuria and it was found statistically significant (X2=5.266, p=0.036) (Table 14).

Table 14: Recurrent haematuria after treatment Treatment

Diagnosis Normal Saline and Normal Saline X2 P-value Dutasteride Irrigation only

Yes No Yes No

BPH 4(16.7) 20(83.3) 15(60.0) 10(40.0) 9.685 0.003 CaP 1(8.3) 11(91.7) 7(50.0) 7(50.0) 5.266 0.036 Total 5 31 22 17 14.691 0.000

CHAPTER 6