|Year : 2020 | Volume
| Issue : 1 | Page : 49-53
Lower urinary tract symptoms in patients with advanced prostate cancer: What are the outcomes of androgen deprivation therapy?
Idorenyin Cletus Akpayak, Samaila I Shuaibu, Chimaobi G Ofoha, Nuhu K Dakum, Venyir M Ramyil, Victor E Onowa, Christian A Agbo, Lemech E Nabasu, Zingur Z Galam
Department of Surgery, Division of Urology, Jos University Teaching Hospital, Jos, Nigeria
|Date of Submission||21-Sep-2019|
|Date of Acceptance||18-Dec-2019|
|Date of Web Publication||14-Jan-2020|
Dr. Idorenyin Cletus Akpayak
Department of Surgery, Division of Urology, Jos University Teaching Hospital, Jos
Source of Support: None, Conflict of Interest: None
Background: Androgen deprivation therapy (ADT) is accepted as the first-line treatment of advanced prostate cancer. This study sets out to determine the outcomes of ADT in reducing lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer and also to determine the quality of life (QoL) of the patients. Patients and Methods: This was a prospective study carried out at Jos University Teaching Hospital. All consecutive patients who had LUTS due to advanced prostate cancer were recruited into the study. All patients completed the international prostate symptom score (IPSS) questionnaire, including QoL assessment. Post-void residual (PVR) urine, maximum flow rate (Qmax), prostate specific antigen and total prostate volume (TPV) were assessed. The parameters before and at 12 months were compared. Results: Data from 65 patients were analysed. The mean age of the patients was 68.5 ± 8.67 years with an age range of 46–85 years. Four (6.2%) had mild LUTS before AD, and their symptoms remained mild at 12 months of ADT. Twenty-two (33.9%) patients had moderate urinary symptoms. Of this, 10 (18.5%) patients had symptomatic improvement at 12 months of ADT. Of 39 (60%) patients who presented with severe LUTS, 21 (32.3%) had improvement at 12 months of ADT. Before ADT and at 12 months of ADT, the mean IPSS score, mean TPV, Qmax, PVR and mean QoL score were 23 ± 8.8 and 15 ± 8.8 (P < 0.0001); 79.7 ± 51.4 and 73.4 ± 34.3 (P = 0.212); 8.0 ± 4.7 and 11.2 ± 4.4 (<0.001); 209.8 ± 127.8 and 163 ± 111.4 (<0.001); 4.23 ± 1.2 and 3.24 ± 1.2 (P < 0.001), respectively. Of the 39 patients (60%) with severe urinary symptoms, 18 (27.7%) of patients had urethral catheterization for either acute or chronic urinary retention before ADT. At 12 months on ADT, eight patients (12.3.7%) were still on catheter due to failed attempts at trial without catheter. Conclusion: ADT significantly improves urodynamic parameters, IPSS score and IPSS-related QoL. There remains a subset of patients, in whom LUTS persist with negative effects on QoL.
Keywords: Advanced prostate cancer, androgen deprivation therapy, international prostate symptom score, lower urinary tract symptoms
|How to cite this article:|
Akpayak IC, Shuaibu SI, Ofoha CG, Dakum NK, Ramyil VM, Onowa VE, Agbo CA, Nabasu LE, Galam ZZ. Lower urinary tract symptoms in patients with advanced prostate cancer: What are the outcomes of androgen deprivation therapy?. Niger Postgrad Med J 2020;27:49-53
|How to cite this URL:|
Akpayak IC, Shuaibu SI, Ofoha CG, Dakum NK, Ramyil VM, Onowa VE, Agbo CA, Nabasu LE, Galam ZZ. Lower urinary tract symptoms in patients with advanced prostate cancer: What are the outcomes of androgen deprivation therapy?. Niger Postgrad Med J [serial online] 2020 [cited 2020 Feb 23];27:49-53. Available from: http://www.npmj.org/text.asp?2020/27/1/49/275808
| Introduction|| |
Prostate cancer is the most commonly diagnosed cancer in men globally. It is commoner in blacks and is the most common cancer in Nigerian men., Furthermore, in Nigeria prostate cancer is the leading cause of cancer death in men. It could present without symptoms, discovered through screening or diagnosed incidentally following transurethral resection of the prostate (TURP). It could also present with symptoms of locally advanced disease such as lower urinary tract symptoms (LUTS), haematuria, pain, urinary retention, urinary incontinence, haematospermia, painful ejaculation, anejaculation, constipation and/or haematochezia. Patients could also present with the symptoms of metastasis. Most of our patients present with features of advanced prostate cancer and are usually treated with androgen deprivation therapy (ADT).,
LUTS are very common in aging men. In prostate cancer, LUTS is attributed mainly to the invasion of the proximal urethra and bladder neck, leading to bladder outlet obstruction (BOO).
ADT should improve LUTS remarkably and therefore the quality of life (QoL) in advanced prostate cancer patients. The therapy can reduce total prostate volume (TPV), reduce BOO, and therefore improves LUTS in patients with prostate cancer. However, in some patients LUTS, with associated poor QoL persists, adversely affecting functionality and productivity. Some patients progress to urinary retention, necessitating insertion of urethral catheter and may become catheter dependent leading to dissatisfaction with treatment outcome. Data on the outcomes of ADT on LUTS and QoL of the patients are lacking in our subregion.
This study sets out to determine the outcomes of ADT in reducing LUTS in patients with advanced prostate cancer and also QoL of the patients.
| Patients and Methods|| |
This was a hospital-based prospective descriptive study carried out at Jos University Teaching Hospital (JUTH) between 2nd January 2017 and 2nd July 2019. Patients with advanced prostate cancer presenting to the urology division at the surgical out-patient department of JUTH with LUTS who subsequently had ADT (orchidectomy or gonadotropin-releasing hormone [GnRH] analogue) were the partiipants of this study. For this study, patients with advanced prostate cancer were those who had clinical features of locally advanced or metastatic diseases.
Patients with LUTS due to neurogenic causes as well as LUTS from other causes and patients who developed castration-resistant prostate cancer during the period of follow-up were excluded from the study. Consent for the study was obtained from the Research and Ethical Committee of JUTH. Informed consent was obtained from patients who fulfilled the criteria for inclusion in the study.
Sample size calculation: Going through the urology record in JUTH for 2014–2016, the number of new patients who presented with urethral stricture was 46, 47 and 50 for 2014, 2015 and 2016, respectively. The annual mean of new patients presenting at the urology clinic with this condition within this period was 48. The proportion of new patients with advanced prostate cancer of the total number of new patients that present annually at the urology clinic at JUTH within this period was 18%.
The projected sample size required to answer the set objectives at 95% confidence level was calculated from the formula below.
- n = the desired sample size
- Z = the standard normal deviation corresponding to 95% level of confidence. The value obtained from the normal distribution is 1.96.
- p = the proportion of patients with urethral stricture that presents in the urology unit of JUTH, estimated at 18% (0.18).
q = 1 – p
q = 1 – 0.18
q = 0.82
∂2 = degree of accuracy desired (i.e. precision) is set at 10% (0.1)2
Therefore, the desired sample size n = 60.
We recruited 102 patients and a total of 37 patients were lost to follow-up. We, therefore obtained information from 65 patients and subjected the data to analysis. With respect to the margin of error this met our desired sample size.
Patients had full clinical evaluation and data entered into a pro forma. A full history was obtained and physical examination including digital rectal examination was carried out at first presentation and at follow-up visits.
All patients completed the international prostate symptom score (IPSS) questionnaire comprising the following questions: Q1 – incomplete emptying, Q2 – frequency, Q3 – intermittency, Q4 – urgency, Q5 – weak stream, Q6 – straining, Q7 – nocturia, (each question is scored 0–5, maximum total score is 35). Mild, moderate and severe LUTS were defined as an IPSS score of 1–7, 8–19 and 20–35, respectively. The QoL would be assessed by the degree of 'bother' as embedded in the IPSS-QoL questionnaire.
Patients who could not complete the questionnaires on their own were assisted by a senior registrar or a consultant in the division. The TPV was estimated with abdominal ultrasonography. The transabdominal ultrasound was carried out by a single experienced radiologist to reduce inter-observer error. The measurement was done by computing the ellipsoid formula which calculates the size by multiplying the largest anteroposterior height (H), transverse width (W), cephalocaudal length (L) by a constant (H × W × L × п/6). Maximum flow rate (Qmax), prostate-specific antigen (PSA) and post-void residual urine (PVR) were assessed. The parameters before and at 12 months of ADT were compared.
The data were analysed using SPSS® version 21 (IBM Corporation, Armonk, New York, US) statistical software with the assistance of a medical statistician. The mean, range and standard deviation for the age distribution of the patients with advanced prostate cancer were calculated. The mean prostate volume, the IPPS, Qmax, PVR; before and at 12 months of ADT were computed and compared, P < 0.05 was considered statistically significant. The percentage of patients with persistent LUTS was computed.
| Results|| |
One hundred and two patients who met the inclusion criteria for the study were recruited into the study and followed up for 12 months. A total of 27 patients were lost to follow-up, while 10 died from various causes. Data from 65 patients were analysed.
The mean age of the patients was 68.5 ± 8.67 years with an age range of 46–85 years. The majority of the patients were in the 61–70 (40%) year age group. The mean Gleason score was 7.1 ± 1.7. Fifty-two (80%) patients had orchidectomy, while 13 (20%) had GnRH analogue.
The patients had LUTS of varying severities. Four patients (6.2%) had mild LUTS before ADT and remain mild at 12 months of ADT. Twenty-two (33.9%) patients had moderate urinary symptoms. Of this, 10 (18.5%) patients had satisfactory symptomatic improvement at 12 months of ADT. Furthermore, of 39 (60%) patients who presented with severe LUTS, 21 (32.3%) had satisfactory improvement at 12 months of ADT [Table 1]. The mean IPSS score before and at 12 months of ADT was 23 ± 8.8 and 15 ± 8.8 (P < 0.0001). The effects of ADT on mean PSA, PVR, Qmax and TPV changes at 12 months following commencement of the ADT, and the mean IPSS score are in [Table 2].
|Table 1: Changes observed within the symptom groups (mild, moderate and severe lower urinary tract symptom) before and at 12 months of androgen deprivation therapy|
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|Table 2: Comparison of parameters before and after androgen deprivation therapy at 12 months|
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All patients reported the effect of the disease on QoL of variable grades. The mean QoL score before and after ADT was 4.23 ± 1.2 and 3.24 ± 1.2 (P < 0.001). Up to 50 patients reported QoL score of 3 and above after ADT.
Of the 39 patients (60%) with severe urinary symptoms, 18 (27.7%) of patients had urethral catheter inserted for either acute urinary retention or chronic urinary retention before ADT. At 12 months on ADT, 8 patients (12.3.7%) were still on catheter following failed attempts at trial without catheter (TWOC).
| Discussion|| |
Our study found that 6.2%, 33.9% and 60.0% of our patients (n = 65) presented with mild, moderate and severe LUTS, respectively. Hence, most of our patients presented with severe LUTS. Lehrer et al. in a study of a cohort of patients with prostate cancer found that most of their patients (55.6%) presented with mild LUTS, 37.1% had moderate LUTS, while 7.3% presented with severe symptoms. The difference in presentation could be explained by the fact that our patients presented in the later stages of the diseases than their patients.
We also found that 27.7% of the patients that presented with severe LUTS had significant improvements in their symptoms at 12 months of ADT. Washino et al. in a similar study found 35% of their patients (n = 42) experienced satisfactory LUTS relief after ADT.
Furthermore, our study found a significant mean reduction in IPSS score at 12 months of ADT with a mean IPSS score improvement by 8 (P < 0.001) which goes to support the significant reduction in LUTS. This finding is similar to that of Andersonet al. who recorded an improvement of 8.6 in the mean total IPSS score in their patients.
In addition, we found a mean maximum flow rate (Qmax) increased from 8.0 to 11.2 ml/s (P < 0.001) and PVR urine significantly reduced from 209.8 to 163.3 ml. Choiet al. also in their assessment of ADT prostate size and voiding symptoms in a cohort of prostate cancer patients in Korea recorded Qmax increase from 8.62 to 11.50 ml/s and a significant PVR reduction by 29.34 ml. The overall effects of ADT on these urodynamic parameters explain the improvement in LUTS in patients with advanced prostate cancer.
ADT is not only cytostatic but also cytotoxic to prostate cancer cells. This may lead to TPV. Our study recorded mean total reduction in TPV of 10.0% (P = 0.212). Carpentier and Schroder found a 57% reduction of TPV in the first 3 months of ADT in a cohort of patients followed up by transrectal ultrasonography. Other workers recorded a more variable mean reduction ranging from 18% to 43%.,,, Therefore, the effect of ADT on prostate volume varies and may be incomplete. This variation may be due to prostate volume before ADT. The initial prostate size before ADT has been found to correlate significantly with a percentage reduction of prostate size in patients with prostate cancer. It is reported that patients with larger prostate volumes have a greater reduction in TPV compared with patients with smaller glands. The variation may also be due to the use of complete androgen blockade (CAB) in some of the previous reports. CAB leads to a higher reduction in TPV compared to GnRH or bilateral orchidectomy monotherapy.,,
LUTS persist in some patients on ADT, become progressive and may lead to acute or chronic urinary retention affecting the QoL. We found in our study that of the 39 (60%) who started with severe LUTS 18 (27.7%) still had severe LUTS at 12 months on ADT with 10 of the patients failing TWOC Sun et al. in the evaluation of 42 patients with advanced prostate cancer on ADT also found persistence of LUTS varying in degrees of severities in some of their patients.
Our study showed that The QoL score (4.2 ± 1.2 vs. 3.2 ± 1.2, P < 0.001) before and following ADT at 12 months showed a statistically significant difference. That shows improvement in QoL score by 1. Andersonet al. and et al. their study recorded mean improvement in QoL by 0.6 which is similar to our finding. However, the mean score of 3.2 ± 1.2 at 12 months following ADT clinically denotes that some patients were still 'bothered' by their symptoms. In other words, the patients had 'mixed' feeling about their symptoms. Furthermore, the difference is not likely to apply to those whose symptoms progressed or failed TWOC. The negative impact on QoL by LUTS has been demonstrated using different QoL tools by many authors.,,
Patrikidou et al. in their work demonstrated that the presence of LUTS in patients with advanced prostate cancer necessitates frequent hospital admissions, require palliative procedures and lower QoL. Also, Sehgal et al. in their study assessed the need for palliative transurethral prostatic resection in patients with advanced carcinoma of the prostate. They found that of the 191 patients with advanced CAP and on ADT 42 (22%) of required channel TURP to relieved severe LUTS at a mean follow-up of 35.5 months.
Furthermore, Zhang et al. randomised patients with severe LUTS into two groups of 45 each. One group received ADT and the other received ADT plus tamsolusin for a duration of 24 weeks. They found that ADT plus tamsulosin had a greater impact on total IPSS, Qmax, QoL and PVR than ADT monotherapy.
We recommend that for the patients with unsatisfactory improvement in LUTS shout be offered additional treatment (Channel TURP or alpha-blocker) to improve their QoL.
Our study is not without limitations. This has to do with the choice of instrument for QoL assessment. There are different tools for the assessment of QoL in patients. However, none of the tools is universally accepted for this evaluation. Our study used the IPSS-QoL assessment and therefore only focussed on LUTS impact on QoL. Many more things like side effects of ADT, orchidectomy may have also impacted on QoL in this group of patients.
| Conclusion|| |
ADT significantly improves urodynamic parameters, IPSS score and IPSS-related QoL. However, there remain clinically significant subsets of patients, in whom LUTS persist with negative effects on QoL.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al
. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.
Ogunbiyi JO, Shittu OB. Increased incidence of prostate cancer in Nigerians. J Natl Med Assoc 1999;91:159-64.
Mohammed AZ, Edino ST, Ochicha O, Gwarzo AK, Samaila AA. Cancer in Nigeria: A 10-year analysis of the Kano cancer registry. Niger J Med 2008;17:280-4.
Osegbe DN. Prostate cancer in Nigerians: Facts and nonfacts. J Urol 1997;157:1340-3.
Ikuerowo SO, Omisanjo OA, Bioku MJ, Ajala MO, Mordi VP, Esho JO. Prevalence and characteristics of prostate cancer among participants of a community-based screening in Nigeria using serum prostate specific antigen and digital rectal examination. Pan Afr Med J 2013;15:129.
Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int 2011;108:1132-8.
Axcrona K, Aaltomaa S, da Silva CM, Ozen H, Damber JE, Tankó LB, et al
. Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: Degarelix vs. goserelin plus bicalutamide. BJU Int 2012;110:1721-8.
Annual Health Record Statistics, Health Records, Jos University Teaching Hospital;.2014-2016;6:9-15.
Araoye OM. Subject selection. In: Araoye OM. Research Methodology with Statistics for Health and Social Sciences, 1st
ed. Illorin: Nathan Publishers; 2003. p. 117-9.
Nunzio CD, Autorino R. Assessing LUTS/BPO: What is the evidence? In: Chapple CR, Tubaro A, editors. Male LUTS/BPH Made Easy. 1st
ed. New York. Springer; 2014. p. 33-54.
Lehrer S, Stone NN, Droller MJ, Stock RG. Association between American Urologic Association (AUA) urinary symptom score and disease stage in men with localized prostate cancer. Urol Oncol 2002;7:73-6.
Washino S, Hirai M, Saito K, Kobayashi Y, Arai Y, Miyagawa T. Impact of androgen deprivation therapy on volume reduction and lower urinary tract symptoms in patients with prostate cancer. Low Urin Tract Symptoms 2018;10:57-63.
Anderson J, Al-Ali G, Wirth M, Gual JB, Gomez Veiga F, Colli E, et al
. Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: Results from a phase IIIb study (NCT00831233). Urol Int 2013;90:321-8.
Choi H, Chung H, Park JY, Lee JG, Bae JH. The influence of androgen deprivation therapy on prostate size and voiding symptoms in prostate cancer patients in Korea. Int Neurourol J 2016;20:342-8.
Labref F, Belanger A, Luu-The V, Labrie C, Simard J, Cusan L, et al
. Gonadotropin releasing hormone agonists in the treatment of prostate cancer. Endocr Rev 2005;26:361-79.
Carpentier PJ, Schroder FH. Transrectal ultrasonography in the follow up of prostate carcinoma patients: A new prognostic parameter? J Urol 1984;131;903-5.
Hand JR. Conservative operations for carcinoma of the prostate: Analysis of 109 cases. J Urol 1950;64:123-48.
Hand JR. Analysis of factors influencing survival of 109 men with carcinoma of the prostate treated conservatively. Trans Am Assoc Genitourin Surg 1973;65:84-99.
Varenhorst E, Alund G. Urethral obstruction secondary to carcinoma of prostate: Response to endocrine treatment. Urology 1985;25:354-6.
Mommsen S, Petersen L. Transurethral catheter removal after bilateral orchiectomy for prostatic carcinoma associated with acute urinary retention. Scand J Urol Nephrol 1994;28:401-4.
Whittington R, Broderick GA, Arger P, Malkowicz SB, Epperson RD, Arjomandy B, et al
. The effect of androgen deprivation on the early changes in prostate volume following transperineal ultrasound guided interstitial therapy for localized carcinoma of the prostate. Int J Radiat Oncol Biol Phys 1999;44:1107-10.
Wilson S. Downsizing and prostate cancer. Rev Urol 2004;6 Suppl 7:S19-24.
Gleave ME, Goldenberg SL, Chin JL, Warner J, Saad F, Klotz LH, et al
. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: Biochemical and pathological effects. J Urol 2001;166:500-6.
Langenhuijsen JF, van Lin EN, Hoffmann AL, Spitters-Post I, Alfred Witjes J, Kaanders JH, et al
. Neoadjuvant androgen deprivation for prostate volume reduction: The optimal duration in prostate cancer radiotherapy. Urol Oncol 2011;29:52-7.
Sanghani MV, Schultz D, Tempany CM, Tiltebaum D, Renshaw AA, Loffredo M, et al
. Quantifying the change in endorectal magnetic resonance imaging-defined tumour volume during neoadjuvant androgen suppression therapy in patients with prostate cancer. Urology 2002;167:2443-7.
Sun S, Bai Y, Yang H, Yang HW. Investigation on lower urinary tract symptoms (LUTS) in elderly patients with prostate cancer (PC) received endocrine therapy. Arch Gerontol Geriatr 2015;60:535-7.
Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, et al
. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: Results of the EPIC study. Eur Urol 2006;50:1306-14.
Lee YS, Lee KS, Jung JH, Han DH, Oh SJ, Seo JT, et al
. Prevalence of overactive bladder, urinary incontinence, and lower urinary tract symptoms: Results of Korean EPIC study. World J Urol 2011;29:185-90.
Fitzpatrick JM. The national history of benign prostate hyperplasia. BJU Int 2006;97:3-6.
Patrikidou A, Brureau L, Casenave J, Albiges L, Di Palma M, Patard JJ, et al
. Locoregional symptoms in patients with de novo
metastatic prostate cancer: Morbidity, management, and disease outcome. Urol Oncol 2015;33:202.e9-17.
Sehgal A, Mandhani A, Gupta N, Dubey D, Srivastava A, Kapoor R, et al
. Can the need for palliative transurethral prostatic resection in patients with advanced carcinoma of the prostate be predicted? J Endourol 2005;19:546-9.
Zhang T, Wu H, Liu S, He W, Ding K. Clinical evaluation of tamsulosin in the relief of lower urinary tract symptoms in advanced prostate cancer patients. Int Urol Nephrol 2017;49:1111-7.
[Table 1], [Table 2]