VOLUME 3; ISSUE 3 2024 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE This publication is intended for registered healthcare professionals only.
UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
VOLUME 3; ISSUE 3 2024 Editor Prof Shingai Mutambirwa - Urologist MBChB, MMed (Urology) Medunsa Head of Urology - Sefako Makgatho Health Sciences University Chairman - The South African Urological Association Academic committee Chairman - Medical and Scientic Advisory Board of The Prostate Cancer Foundation Editorial Board Dr. Sheynaz Bassa - Clinical and Radiation Oncologist MBChB (Univ of Natal), FC Rad (Onc) SA Head of Department: Radiation Oncology Steve Biko Academic Hospital and The University of Pretoria Dr Jireh Serfontein - Medical Sexologist MBChB (Pret.), Dip HIV Management, MMed Sexual Health (Univ. Sydney) Clinical head: My Sexual Health Pretoria Editorial and Publishing Ofce Maria Philippou Randburg 2194 Enquiries 082 3355 444 Publisher Maria Philippou Andrew Oberholzer Disclaimer All rights reserved. No editorial matter published in Urology, Urooncology and Sexology Update may be reproduced in any form or language without written permission from the publishers. While every effort is made to ensure accurate reproduction, the Prostate Cancer Foundation, the authors, publishers and their employees or agents shall not be responsible or in any way liable for any errors, omissions or inaccuracies in the publication whether arising from negligence or for any consequences arising there from. The inclusion or exclusion of any product does not mean that the Prostate Cancer Foundation, the publisher or the editorial board advocates or rejects its use either generally or in any particular eld or elds. This publication is intended for registered healthcare professionals only. If you received this publication or a link to this publication in error, please do not directly or indirectly use, print, copy, forward, or disclose any part of this publication. Please delete the copy or link to the publication and notify the publisher. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE CONTENTS 1 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Supported by: SOUTH AFRICAN PROSTATE CANCER GUIDELINES Vs 04 OCTOBER 2024 METASTATIC HORMONE SENSITIVE PROSTATE CANCER (mHSPC) Suit Up Saturday at the September SAUA PAUSA Congress ADVERTORIAL ERLEADA® in mHSPC Evaluation of Usefulness of Propiverine Hydrochloride in Poor Responders to Previous Anticholinergics Thanks to Everyone Who Supported The Prostate Cancer Foundation's Suit Up September Campaign to Help Raise Awareness About Prostate Cancer Talking castrate resistant prostate cancer and PARP inhibitors with Prof Shingai Mutambirwa Thanks to our member companies for Suiting Up A quick take on the TRAVERSE trial ndings: Cardiovascular Safety of Testosterone-Replacement-Therapy Why the Cancer Alliance has launched a court case against the Gauteng Department of Health,for their failure to provide timeous radiation oncology services to cancer patients at Charlotte Maxeke Hospital The Prostate Cancer Foundation and Astellas team up to make prostate cancer screening more accessible for South African men Swisful Press Realease Closing the gaps in cancer prevention and control: is a national cancer act the solution for South Africa? 2 5 6 8 11 12 15 16 20 22 24 26
2 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Introduction The majority of males in South Africa present with locally advanced and/or metastatic disease at 1,2 presentation. . Data used for recommendations is based on the denition of M1 disease as determined by radiographic imaging and bone scintigraphy due to the lack of data from studies 3 utilising newer more accurate imaging. Disease classication Metastatic disease that occurs after radical local treatment of the primary tumour is classied as 3 metachronous metastatic prostate cancer. Metastatic disease that is rst diagnosed in the advanced stage is classied as de novo or 3 synchronous prostate cancer. Patients with metachronous metastatic disease generally have a better prognosis than patients 3 with synchronous disease. SOUTH AFRICAN PROSTATE CANCER GUIDELINES Vs 04 OCTOBER 2024 METASTATIC HORMONE SENSITIVE PROSTATE CANCER (mHSPC) A full version of the guidelines is available on the Healthcare Professionals Section at: https://prostate-ca.co.za/ Panel Members: Prof. Shingai Mutambirwa - MBChB, MMed (Urology) Medunsa. Head of Urology Sefako Makgatho Health Sciences University. Dr. Lance Coetzee - MBChB (Pret.), MMed (Urol.), F.C.S (Urol.) SA, Fellow in Uro-Oncology (Duke Univ. USA). Urologist in private practice at the Pretoria Urology Institute. Prof. Ahmed Adam - MBChB, Dip PEC (SA), MMed FCS(SA) Urol. Academic Head: Division of Urology (Wits University),Clinical Head (Urology): CMJAH and Cluster Hospitals. Dr Pieter Spies - MBChB (US) MMed (Urol).Consultant Urologist, Tygerberg Hospital, University of Stellenbosch. Dr Jeff John - MBChB (UCT), FC Urol (SA), MMED (Urol). Head of the Division of Urology at Frere Hospital, East London. Dr. Sheynaz Bassa - MBChB (Univ of Natal), FC Rad (Onc) SA. Head of Department: Radiation Oncology Steve Biko Academic Hospital. Dr. Ingo de Muelenare - MBChB (Pret.), Dip ATLS (1994), FC Rad (Onc). SA., MMed (Rad.Onc) Wits, Radiation Oncologist in private practice in Johannesburg and Pretoria. Prof. Mike Sathekge - MBChB, MMed (Nuclear Medicine), Phd, MASSAF. Head of Department: Nuclear Medicine University of Pretoria. Dr Anthony Levy - MBBCh (WITS), BComm (Hons), FCRaD (UCT). Radiologist in private practice in Cape Town. Dr Devon Moodley - MMBch (Wits), FCP (SA) Medical oncologist in private practice in Johannesburg Dr Jireh Serfontein - MBChB (Pret.), Dip HIV Management, MMed Sexual Health (Univ. Sydney), Clinical head: My Sexual Health Pretoria. Dr Chantelle Scott – BSc Hons Genetics (Stell). MSc Med Genetic Counselling (UCT). PhD Human Genetics (Stell). Genetic Counsellor in private practice in Cape Town. Helen Shaw - Dip. in Physiotherapy (Pretoria). Physiotherapist specialising in pelvic dysfunctions in private practice in Cape Town. Daniel Mark Botha - BSc (Hons) Biokinetics. Biokineticist in private practice in Johannesburg. Metastatic PCa is classied as high or low volume and/or high or low risk based 3 on the CHAARTED and LATITUDE studies. High Low CHAARTED (volume) > 4 Bone metastases including > 1 outside the vertebral column or pelvis AND/OR Visceral metastasis (lymph nodes are not classied as visceral metastases) Not high LATITUDE (risk) > 2 high-risk features of: > 3 Bone metastasis Visceral metastasis > ISUP grade 4 Not high
3 3 Prognostic groups based on PSA levels Based on a large SWOG 9346 cohort, the PSA level after 7 months of ADT was used to create 3 prognostic groups: PSA after 7 months after start of ADT Median survival on ADT monotherapy < 0.2 ng/mL 75 months 0.2 ≤ 4 ng/mL 44 months > 4 ng/mL 13 months Treatments for hormone sensitive metastatic prostate cancer Primary androgen deprivation therapy (ADT) has been the standard of care for over 50 years.3 However, the advent of the androgen receptor pathway inhibitors (ARPIs) and the introduction of chemotherapy earlier in the treatment pathway for high volume disease has improved patient survival and outcomes considerably, and ADT as monotherapy is now no longer considered 3 standard of care. First line Treatment Surgical castration with a bilateral orchiectomy or chemical castration with the use of a LHRH agonist or LHRH antagonist all achieve similar oncological 3 outcomes. For men who present with metastases at the time of diagnosis (synchronous disease) ADT monotherapy is no longer considered standard of care, and wherever possible ADT should be combined with a new androgen receptor pathway inhibitor (ARPI) 3 on initiation of ADT (doublet therapy). The addition of docetaxel to ADT plus an ARPI (triplet therapy), improves overall survival in patients with synchronous high-volume disease. This option should be based on tness for chemotherapy, patient preference, side effects, availability of 3 docetaxel and logistics. Recommended androgen deprivation therapy options Patient prole Preferred Treatment Option Recommended for men who require a rapid reduction of testosterone for complications such as spinal cord compression 3 and/or urinary retention Recommended for men who are unable to access a urology or oncology department or an appropriate healthcare professional at the required intervals for injectable ADT drugs 3 Bilateral orchiectomy Recommended for men with pre-existing cardio-vascular 3 disease or cardiovascular risk factors 3 LHRH antagonists 3 Recommended for all other men 3 LHRH agonists 3 Combine with bicalutamide for 2-4 weeks to prevent testosterone are when necessary Early versus deferred androgen deprivation therapy Early treatment before the onset of symptoms is recommended in the majority of patients with metastatic hormone-sensitive disease, as data indicates that early intervention probably extends time to death for any cause and time to death 3 from prostate cancer (Pca). Deferring treatment for patients with metastatic prostate cancer should only be considered in men who are asymptomatic and who express a strong 3 desire to avoid treatment-related side effects. Men should be counselled about the increased risks of developing symptoms and of dying from cancer by deferring treatment.3 However, this data is based on conventional imaging, and newer imaging technologies may identify patients with oligometastatic disease who could benet from metastases directed therapy in order to delay ADT. Patients who wish to delay the initiation of ADT must 3 be willing to commit to regular follow ups. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
4 Before commencing with ADT patients should undergo the following: • a comprehensive history and physical examination that includes falls risk and height 4 measurement prior to initiating ADT • a full baseline cardiometabolic health risk assessment and monitoring for cardiovascular 4 complications whilst receiving ADT • an evaluation of bone mineral density with a 4 DEXA scan • clinicians should obtain baseline calcium and 4 25-hydroxyvitamin D levels at the start of ADT Non-steroidal anti-androgen monotherapy with bicalutamide Bicalutamide is an oral non-steroidal antiandrogen. For patients with M1 disease it has been shown to be less effective in terms of overall survival, clinical progression, and treatment failure than ADT monotherapy and is therefore not 3 recommended as standard of care. Combined androgen blockade with bicalutamide This treatment offers a small survival advantage (< 5%) over ADT monotherapy with increased side effects. It is inferior to the newer combination therapies with ARPIs and should therefore only be 3 used if an ARPI is unavailable. Intermittent versus continuous androgen deprivation therapy This option should only be considered for men who are the best PSA responders and for whom survival is considered secondary to quality of life. Results from the SWOG 9346 trial did not show that intermittent ADT was inferior to continuous ADT in terms of overall survival, but continuous ADT in combination with an ARPI has become the 3 standard of care. Close monitoring of PSA and testosterone levels and possibly imaging is required when using intermittent ADT, especially during off-treatment periods, and patients may need to switch to continuous ADT if there are signs of disease 5 progression. Combination therapy with an androgen receptor pathway inhibitor (ARPI) - New standard of care Combination of ADT together with either abiraterone acetate plus prednisone, enzalutamide or apalutamide improves overall survival, time to radiographic progression, time to 3 pain, and time to chemotherapy. For optimal treatment outcomes this doublet therapy should be implemented on initiation of ADT in men who are t enough and is now regarded as standard of care 3 for the treatment of m(HSPC). Combination therapy with docetaxel for de novo high-volume m(HSPC) For de novo metastatic high-volume hormone sensitive prostate cancer, the use of ADT combined with docetaxel upfront improves survival. However, the overall survival benet is further improved by adding an ARPI to ADT and docetaxel (triple 3 therapy). Combining docetaxel alone with ADT should only be considered if no ARPI is available or all available ARPIs are contraindicated. Usage of docetaxel should be reserved for men who are t enough for 3 chemotherapy. Treatment of the primary tumour in newly diagnosed m(HSPCA) In men with newly diagnosed m(HSPCA) the addition of radiotherapy to the primary tumour increases overall survival in low volume disease 3 only. It is therefore recommended in this situation 3 and not for unselected patient groups. References: 1 Benedict MOA, Steinberg WJ, Claasen F, et al. The prole of Black South African men diagnosed with prostate cancer in the Free State, South Africa. S Afr Fam Pract (2004). 2023 Jan 10;65(1). 2 Le Roux HA, Urry RJ, Sartorius B et al. Prostate Cancer at a regional hospital in South Africa: we are only seeing the tip of the iceberg. South African Journal of surgery. 01 Dec 2015, 53(3 and 4):57-62 3 EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6. Available at: https://uroweb.org/guidelines/prostatecancer/summary-of-changes/2023 4 Kokorovic A, So AI, Serag H, et al. Canadian Urological Association Guideline on androgen deprivation therapy: Adverse events and management strategies. Can Urol Assoc J 2021;15(6).E307-22. http://dx.doi.org/10.5489/cuaj.7355. 5 NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 4.2023 — September 7, 2023. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
5 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Suit Up Saturday at the September SAUA PAUSA Congress Dr Pieter Spies from Tygerberg's Urology Department Dr Smit Van Zyl from Polokwane Dr Stephen Cornish from Sunninghill Thanks to Bionike and the organisers we were able to hold a Suit Up Saturday competition. Thanks to all who participated. PCF's CEO Andrew Oberholzer with Bionike's sales representative Zanele Bionike prizes for Suit Up Saturday Dr Hugo Van Der Merwe from The Urology Hospital with PCF's CEO Andrew Oberholzer Winner of the best suited up man award Dr James Urry receives his Bionike prize hamper from PCF's CEO Andrew Oberholzer Winner of the best suited up lady award Dr Fhatu Sikhitha from Sekako Makgatho Health Sciences University receives her Bionike prize hamper from PCF's CEO Andrew Oberholzer Groote schuur Urology Department doctors Thanks to Bionike and Dischem for providing the Suit Up Saturday prizes
6 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE ® ERLEADA (Apalutamide) in Metastatic Hormone-Sensitive Prostate Cancer Androgen deprivation therapy (ADT) has long been the standard of care for metastatic 1 hormone-sensitive prostate cancer (mHSPC). However, despite initial responses, many patients eventually develop resistance to ADT, 1 leading to disease progression. The introduction of androgen receptor pathway inhibitors (ARPIs) (abiraterone, apalutamide and enzalutamide) has changed the treatment landscape of mHSPC, demonstrating improved survival benets with additional androgen 1 receptor suppression when added to ADT. ® ERLEADA (apalutamide) is an orally administered, selective Androgen Receptor (AR) inhibitor indicated for the treatment of 2 mHSPC in combination with ADT. It binds directly to the ligand-binding domain of the AR, preventing AR nuclear translocation, inhibiting DNA binding and impeding AR-mediated 2 transcription. This mechanism underpins its efcacy in extending survival in patients with mHSPC, as demonstrated in the pivotal phase 3 3, randomised, multinational TITAN study. TITAN study ndings TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) enrolled over 1000 mHSPC patients, including those with highvolume or low-volume disease, previous docetaxel use, previous treatment for localised disease, and previously or newly diagnosed 3 disease. Patients were randomised to ® treatment with ERLEADA or placebo added to 3 ® ADT. ERLEADA plus ADT signicantly prolonged median radiographic progression-free survival (rPFS), median overall survival (OS) and the median time to cytotoxic chemotherapy relative to placebo plus ADT, with benecial effects on median rPFS and median OS 3 consistent across various subgroups. The safety prole did not differ notably between the two groups, and health-related quality of life was ® 3 preserved during ERLEADA treatment. TITAN ® underscores ERLEADA 's broad applicability in mHSPC and extends treatment options available for standard of care in this patient 1,3 population. Real-world evidence While clinical trials provide controlled environments to assess the efcacy and safety of new therapies, real-world evidence (RWE) offers valuable insights into how these 4 treatments perform in routine clinical practice. Recent RWE studies, such as the OASIS and ROME studies, have further solidied the role of ® ERLEADA in treating mHSPC, particularly in 5,6 comparison to enzalutamide. OASIS study ndings The OASIS study, a retrospective observational cohort study, evaluated clinical outcomes among patients with mHSPC using the 5 ConcertAI RWD 360 prostate cancer dataset. This comprehensive analysis included over 2 700 patients with newly diagnosed mHSPC, providing a robust dataset to evaluate the real5 world impact of various treatment regimens. The study revealed that patients initiating ® treatment with ERLEADA + ADT had signicantly better outcomes than those treated with other androgen receptor pathway inhibitors (ARPIs), docetaxel + ADT, or ADT ADVERTORIAL ERLEADA® in mHSPC
7 5 alone. Notably, the risk of developing castration resistance was signicantly reduced ® in patients starting with ERLEADA + ADT compared to ADT alone (adjusted hazard ratio 5 [aHR] 0.36, 95% CI 0.19-0.67; p=0.0016). Moreover, overall survival was longer in ® patients treated with ERLEADA + ADT compared to those receiving enzalutamide + ADT (aHR 0.48, 95% CI 0.23-0.99; p<0.05) or abiraterone acetate/prednisone + ADT (aHR 5 0.43, 95% CI 0.21-0.90; p<0.05). The OASIS study highlights the importance of ® starting treatment with ERLEADA + ADT in patients with mHSPC to maximise clinical 5 outcomes. ROME study insights Complementing the OASIS study, the ROME study provided additional RWE supporting the ® 6 use of ERLEADA over enzalutamide. This study focused on survival outcomes among men with mHSPC who initiated treatment with either ® 6 ERLEADA or enzalutamide. The ROME study utilised data from the Flatiron Metastatic Prostate Cancer Core Registry over a period of 6 10 years. The study reported that by 24 months post-initiation, a signicantly higher proportion ® of patients treated with ERLEADA survived compared to those treated with enzalutamide 6 (85.4% vs. 73.9%; p=0.030). This survival benet ® highlights ERLEADA 's efcacy in a real-world setting, supporting its use as a rst choice ARPI 6,7 in mHSPC. Conclusion The convergence of clinical trial data and ® real-world evidence underscores ERLEADA 's 3,5,6 efcacy in treating mHSPC. The TITAN trial, alongside real-world studies like OASIS and ® ROME, has established ERLEADA as a valuable addition to the treatment strategy for 3,5,6,7 mHSPC. With its demonstrated ability to extend survival, delay disease progression, and ® offer a manageable safety prole, ERLEADA stands out as a valuable tool in the oncologist's 3 armamentarium. References: 1. Hoy SM. Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Drugs 2020;80:1579-1585. DOI: https://doi.org/10.1007/s40265-020-01401-0. 2. ERLEADA® professional information, March 2023. 3. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019;381:13-24. DOI: 10.1056/NEJMoa1903307. 4. Dang A. Real-World Evidence: A Primer. Pharm Med 2023;37:25-36. DOI: https://doi.org/10.1007/s40290022-00456-6. 5. Maughan BL, Mundle S, Nematian-Samani M, et al. Survival Outcomes of APA as a Starting Treatment: Impact in Real-World Patients with mHSPC (OASIS). J Clin Oncol 2024;42(4 Suppl):65. DOI: https://doi.org/10.1200/JCO.2024.42.4_suppl.65. 6. Bilen MA, Du S, Khifeh I, et al. Real-world survival of men with metastatic castration-sensitive prostate cancer (mHSPC) initiated on apalutamide (APA) or enzalutamide (ENZ) in an oncology database: ROME Study. J Clin Oncol 2024;42(4 Suppl):57. DOI: https://doi.org/10.1200/JCO.2024.42.4_suppl.57. 7. Boukovala M, Spetsieris N, Efstathiou E. An evaluation of apalutamide for the treatment of prostate cancer, Exp Opin Pharmacother 2020;21(13):15371546, DOI: 10.1080/14656566.2020.1770726. ® S4 ERLEADA 60 mg lm-coated tablets. Each lm-coated tablet contains 60 mg of apalutamide. Reg. No.: 53/21.12/0453. For full prescribing information refer to the ® approved ERLEADA Professional Information (March 2023). Further information available on request from Market Authorisation Holder. JANSSEN PHARMACEUTICA (PTY) LTD (Reg. No. 1980/011122/07), 2 Medical Street, Halfway House, Midrand 1685. www.janssen.com. Medical Info Line: 0860 11 11 17. CP-475684 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
8 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE This article is a summary of the article: “Evaluation of usefulness of propiverine hydrochloride in poor responders to previous anticholinergics.” By Naoya Masumori, Yuya Funato, Yasunobu Yamaguchi and Kunio Itoh. Published in LUTS (2018) 10, 116–12. Anticholinergic therapy is a popular treatment option for pollakisuria/urinary incontinence. There are a number of anticholinergics available but not all patients respond well to treatment. Propiverine hydrochloride has anticholinergic activity and calcium antagonistic activity. It has proven efcacy and a good safety prole for overactive bladder when compared with placebo. It has also been shown to be effective in a randomized controlled trial to treat benign prostatic hyperplasia with overactive bladder using an alpha-blocker combined with propiverine hydrochloride. In a previous study evaluating the usefulness of propiverine hydrochloride in poor responders to other anticholinergics, the overactive bladder symptom score (OABSS) was signicantly improved. However, the study involved only 73 subjects, so the authors designed this survey to validate these results in a much larger sample size. Methods Eligibility criteria In this survey 3851 subjects at 680 institutions were enrolled. Patients had pollakisuria and urinary incontinence associated with neurogenic bladder, nervous pollakisuria, unstable bladder, and irritable bladder (chronic cystitis and chronic prostatitis) or with urgency pollakisuria, and urgency incontinence associated with overactive bladder. Patients had to have had at least 4 weeks of treatment with another anticholinergic, which was discontinued due to lack of efcacy as determined by the treating clinician. Administration method and follow-up Patients were given 20 mg of propiverine hydrochloride once daily after meals, but the dosage could be adjusted based on age and symptoms, and the dose could be increased to 20 mg twice daily if necessary. Adverse Events The table below shows the most common adverse drug reactions and numbers of subjects discontinued from treatment Evaluation of Usefulness of Propiverine Hydrochloride in Poor Responders to Previous Anticholinergics
9
10 These side effects are typical for all anticholinergics, and did not differ from those reported in previous surveys. Efcacy The overactive bladder symptom score (OABSS) data before treatment with propiverine hydrochloride and at weeks 4, 8, and 12 of treatment, are shown in the table below together with the effects of treatment on various symptom scores. Conclusion The mean OABSS was 8.92 before previous anticholinergic therapy, 7.92 before treatment with propiverine hydrochloride, and 5.48 at nal evaluation after 12 weeks of treatment on propiverine hydrochloride. This study showed that switching to propiverine hydrochloride is a viable option when patients receive an inadequate treatment response on solifenacin succinate, imidafenacin or tolterodine tartrate. Treatment with propiverine hydrochloride improved the OABSS more markedly than the previous anticholinergics and OABSS improved signicantly for all types of urinary incontinence (urge, mixed, and stress). This effect was observed at all time points and in all subgroups stratied by sex, age, symptoms, and previous anticholinergics. Patients who experienced adverse drug reactions on previous anticholinergic treatment are likely to experience the same adverse events when treated with propiverine hydrochloride. In patients with benign prostatic hyperplasia, propiverine hydrochloride should be used with caution, as voiding difculty may be exacerbated, and residual urine may be increased. Event (MedDRA patient preferred term) Total number of subjects Thirst Constipation Urinary retention Voiding difculty Residual urine volume increased Dry mouth Dizziness Overactive bladder symptom score (OABSS) OABSS in male participants OABSS in female participants Day-time frequency score Night-time frequency score Urgency score Urgency incontinence score Number of subjects with adverse drug reactions 480 184 151 44 38 31 17 12 Before treatment 2932 1610 1322 2932 2932 2932 2932 Incidence of adverse drug reactions (%) 13.25 5.08 4.17 1.21 1.05 0.86 0.47 0.33 Week 4 2668 1458 1210 2663 2667 2662 2665 Number of subjects who discontinued treatment 232 70 56 26 30 13 8 9 Week 8 2078 1165 913 2073 2077 2073 2072 Treatment discontinuation rate (%) 6.40 1.93 1.55 0.72 0.83 0.36 0.22 0.25 Week 12 1823 1001 822 1819 1822 1817 1818 Analysis set: subjects included in the safety evaluation (n = 3624) Analysis set: subjects included in efcacy evaluation (n = 2932) UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
11 Thanks to Everyone Who Supported The Prostate Cancer Foundation's Suit Up September Campaign to Help Raise Awareness About Prostate Cancer September is prostate cancer awareness month and every year The Prostate Cancer Foundation asks people to Suit Up for just one day to help us raise awareness about prostate cancer. Suit Up September badges are sold for R50 to help raise funds for the Prostate Cancer Foundation's activities and projects. Our KZN Patient Affairs Board Chairman Dumisani Pakkies suiting up for a 55km cycle at Virgin Active The team from Panorama Centre for Surgical Oncology suiting up Our Gauteng Patient Affairs Board Chairman Muzi Zulu suiting up at Chris Hani Baragwanath hospital Dr Michael Mol who is the voice behind our Suit Up September campaign Our nuclear medicine technologist volunteer, katlego Sekhwela at Klerksdorp Hospital at the Suit Up day he organised to raise awareness about prostate cancer Comedian Barry Hilton with our Patient Affairs Board Chairman Ian Johnston in Cape Town at one of Barry's shows UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
12 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE With the launch of the rst PARP inhibitor in South Africa there is a lot of discussion about genetics and the shift to precision medicine. Is this the domain of the medical oncologists or do urologists have a role to play here? I think it basically involves everybody. The most important thing is to get the information about the genetic makeup for the patient and that needs to probably be done much earlier in the disease as it can even affect decision making for patients with localised disease. So even before deciding whether a patient is a candidate for active surveillance or a radical prostatectomy or brachytherapy. Research has shown that patients with localised prostate cancer undergoing active surveillance in the United States with germline BRCA1/BRCA2 or ATM mutations were 1.96 times more likely to be upgraded on re-biopsy specimens than prostate cancer patients without pathogenic variants. Patients with a BRCA2 mutation who were on active surveillance (AS) were 2.74 times more likely to have an upgraded Gleason score. This just demonstrates how early genetic testing can inuence treatment decisions. Patients with BRCA1/BRCA2 or ATM are not suitable candidates for AS even if other clinical and pathological features are ne. There is currently no standardisation of the genomic reports from pathology laboratories, and they can be very difcult to interpret, particularly when it comes to BRCA 1 mutations and their relevance for treatment with PARP inhibitors. Do you have any recommendations? There are a lot of challenges. One of them is that there is a shortage of genetic counsellors, so I think everyone, be it medical oncologists, clinical oncologists, urologists and other specialties that are involved with prostate cancer need to actually have a reasonable understanding about genomics and the mutations involved in prostate cancer. I think the bigger issue is going to be about cost, because there are lots of commercial labs that offer different tests, and they all report slightly different information. The tests report on a number of variances and there are some that are clinically signicant and some that are unlikely to be involved. If you do, for example, next generation sequencing, which is basically looking at every gene in the body It can be very expensive, but for the purposes of prescribing PARP inhibitors, we're really just looking at the homologous recombination repair genes (HRR) and the most important ones are BRCA 2 and to a lesser extent BRCA 1. Although having said that, there are some other mutations like ATM and PALB2 which can have an impact. ESMO is currently in the process of drawing up standardised reporting guidelines for pathology labs which will hopefully improve the situation. In the meantime, it's a good idea to make friends with your local pathologist. Talking castrate resistant prostate cancer and PARP inhibitors with Prof Shingai Mutambirwa Prof Shingai Mutambirwa – Urologist MBChB, MMed (Urology) Medunsa Head of Urology - Sefako Makgatho Health Sciences University Chairman - The South African Urological Association Academic committee Chairman - Medical and scientic Advisory Board of The Prostate Cancer Foundation Shingai Mutambiwa is a urologist who is mostly in academic practise. He graduated from Godfrey Huggins School of Medicine in Harare, Zimbabwe and went on to study urology at Medunsa where he obtained a M Med (Urology) in 1996. He is involved in many projects and has a passion for men's health and the development of urology throughout Africa.
13 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
14 It's important to refer to a genetic counsellor before you send patients testing as germline testing can have major implications when applying for life insurance or even a medical aid plan, as there are currently no laws in South Africa to prevent these companies from discriminating against these patients. This is clearly an issue that needs to be taken up with the industry and I know that The Prostate Cancer Foundation is looking into this. In the UK there is a voluntary code on genetic testing agreed between HM Government and the Association of British Insurers that prevents discrimination of patients who have germline mutations.. All the major society guidelines recommend that the new standard of care for metastatic hormone sensitive prostate cancer (mHSPC) is ADT plus an ARPI. So, when these patients progress to the castrate resistant stage, is there a rationale for continuing with the ARPI or using a combination PARP and ARPI or should they have PARP monotherapy? We still have many patients who become castrate resistant and who have been on ADT monotherapy, so for these patients who have the relevant mutations it makes sense to give a combination of a PARP inhibitor and an ARPI. For example, niraparib combined with abiraterone in a single tablet. The research shows that these patients have better outcomes than patients on only an ARPI. However, for patients who have been on ADT plus an ARPI and have progressed to the castrate resistant stage we know that there is not much activity of one ARPI over another. So, if these patients have the relevant genetic mutations, then PARP monotherapy is an option. We're looking at whether there is any benet to continuing with ADT, but that data is not out yet. There doesn't seem to be a lot of data about sequencing with chemotherapy for patients who have progressed to the castrate resistant stage and have relevant genetic mutations that would make them candidates for treatment with a PARP inhibitor. There are no head-to-head trials comparing the sequence of a taxane followed by a PARP inhibitor, or a PARP inhibitor followed by taxane, so we only have some subgroup analysis that was done in the randomized Phase 3 trials. It seems as though there may be a benet to using the PARP inhibitor before chemotherapy but more trials are needed to conrm this. What other developments do you anticipate in the future? There are trials underway looking at PARP inhibitors in combination with ARPIs in the hormone sensitive setting so it's possible that these drugs will be used earlier in the treatment pathway in the future. We should also remember that there are a lot of other drugs in our armamentarium and there's a lot of sequencing required based on various factors. We have to consider a patient's performance status when deciding on the rst-line treatment for mCRPC, because it's going to change and could affect what options are available as the disease progresses. For example, if you want to use radium223 for mCRPC patients, the criteria is that they have symptomatic bone mets and no visceral mets and that they have had docetaxel or couldn't have chemotherapy. If you wait too long to initiate treatment with radium-223, then patients could progress and develop visceral mets, in which case they cannot use this treatment so you lose one option that could have been highly benecial. Also, we have to constantly be aware of the costs of many of these new treatment options. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
15 Thanks to our member companies for Suiting Up Key Oncologics suiting up at the SAUA/PAUSA congress Janssen suiting up at the SAUA/PAUSA congress Accord Healthcare suiting up at their ofces Ferring suiting up at the SAUA/PAUSA congress Astellas suiting up at the SAUA/PAUSA congress Thanks to Bionike and Dischem for providing the Suit Up Saturday prizes UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
16 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE The largest trial to date on testosterone replacement therapy and cardiovascular safety provides some answers and reassurance for clinicians and patients about an issue that lacked data to guide decision making. Background Prior to the publication of this study, the cardiovascular effects of testosterone replacement therapy in middle-aged and older men with hypogonadism was unclear, as previous studies provided conicting results or were too small or of an insufcient duration to provide high level evidence. This led to the FDA issuing a guidance statement which required manufacturers of approved testosterone products to conduct clinical trials to determine whether testosterone replacement therapy is associated with an increased risk of cardiovascular events. Study Design TRAVERSE is a phase 4, multicentre, double-blind, randomized, placebo-controlled, noninferiority trial that assessed the effects of testosterone replacement therapy on the incidence of cardiovascular events among men with hypogonadism and established cardiovascular disease or an elevated cardiovascular risk. The 5246 men, aged 45 to 80 years of age were given either transdermal 1.62% testosterone gel or matching placebo gel. The dose of the testosterone gel was adjusted to maintain testosterone levels between 12.14 and 26 nmol/L. Men had to have: • a preexisting cardiovascular disease or a high risk of cardiovascular disease • at least one symptom of hypogonadism • two fasting testosterone levels of less than 10.40 nmol/L - so these men had mild to moderate hypogonadism • Men with congenital or severe hypogonadism (testosterone < 3.45 nmol/L were excluded Results The mean duration of treatment was 22 months, and the duration of follow-up was 33 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% condence interval, 0.78 to 1.17; P <0.001 for noninferiority). Interestingly, the incidence of prostate cancer was similar in the two groups, however the increase in prostate-specic antigen levels from baseline was greater in patients in the testosterone group than in those in the placebo group. Conclusion In middle-aged and older men with hypogonadism and preexisting cardiovascular disease or an increased cardiovascular risk, treatment with transdermal testosterone on a daily basis for approximately 2 years was noninferior to placebo with respect to the incidence of major adverse cardiac events. A quick take on the TRAVERSE trial findings: Cardiovascular Safety of Testosterone-Replacement-Therapy Published in The New England Journal of Medicine June 16 2023, VOL 389 NO.2 107-117 By Lincoff AM, Bhasin S, Flevaris P, et al.
17 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
18 This is the rst large scale double-blind, randomized, placebo-controlled, noninferiority trial that provides robust evidence on the cardiovascular safety of topical testosterone replacement therapy. The results will enable clinicians to make a more informed evaluation of the potential benets and risks of testosterone therapy for this group of men. Availability of testosterone gel in South Africa Testosterone 1% gel (ANDROGEL®) is currently the only registered testosterone gel in South Africa. Useful Links to further information: https://www.urotoday.com/videolectures/journal-club/video/mediaitem/3579traverse-trial-insights-a-comprehensive-look-attestosterone-replacement-therapy-andcardiovascular-safety-journal-club-rashidsayyid-zachary-klaassen.html https://live.arealive.org/webinars/public/index. html#home Standardising Terminology What terminology should we be using for abiraterone, enzalutamide, apalutamide and darolutamide? These drugs are currently referred to as: • Androgen receptor pathway inhibitor (ARPI) • Androgen receptor signaling inhibitors (ARSI) • Androgen receptor-targeted agents (ARTA) • Second generation androgen receptor pathway inhibitors (SARPI) • New hormonal agents (NHA) • Novel hormonal therapies (NHT) Androgen receptor pathway inhibitor (ARPI) At a recent meeting of the Advanced Prostate Cancer Consensus Conference 58% of the participants voted for this term. This was endorsed by the SAUA. Conclusion This is an appeal to clinicians, presenters and the pharmaceutical industry to use one name for these drugs in South Africa to avoid confusion UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
19 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
20 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE The radiation cancer crisis at Charlotte Maxeke Hospital has been a pressing issue since 2018, when it was rst brought to the attention of the Human Rights Commission. Over the past ve years, the Cancer Alliance has consistently highlighted the inadequacy of radiation oncology services at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Key concerns include the hospital's failure to meet international standards for radiation equipment and stafng, leading to frequent equipment breakdowns and extended waiting times for cancer patients in need of treatment. In November 2021, the Cancer Alliance, in collaboration with the Treatment Action Campaign and SECTION27, marched to the Premier's ofce to demand the establishment of a Task Team to address this ongoing crisis. The neglect of equipment and stafng issues resulted in a signicant backlog of patients waiting for radiation treatment. A medical doctor was appointed by the Cancer Alliance to work alongside the CMJAH Radiation Oncology team, uncovering a backlog of nearly 3,000 patients - most of whom were prostate cancer patients. Some of these individuals have been waiting for treatment since 2016. Patients were categorized based on risk levels, from expedited services for high-risk cases to low-risk patients. Due to the crisis, most patients have been placed on androgen deprivation therapy without receiving further interventions, as CMJAH is unable to provide necessary treatments. In March 2022, the Gauteng Department of Health established a Task Team to develop a comprehensive plan to address the backlog, including the possibility of outsourcing radiation services. However, this initiative has yet to yield meaningful results, with promises of tenders for outsourcing remaining unfullled. In March 2023, the Gauteng Finance Department allocated R784 million from the province's equitable share, with R250 million earmarked for outsourcing radiation services to address the backlog. Despite this, no patients have beneted from this allocation, even though a planning tender for R17 million was awarded in May 2024. The remaining R534 million is designated for addressing equipment shortages related to radiation and surgical backlogs. Additionally, many prostate cancer patients are waiting for radical prostatectomies at either Chris Hani Baragwanath Academic Hospital or Charlotte Maxeke Academic Hospital, neither of which currently offers either open or robotic radical prostatectomy procedures. Training for healthcare professionals in this critical area requires motivation for the necessary equipment and expertise, utilizing both the National Treasury Services Grant (NTSG) and the Statutory Health Professionals Training Grant. Unfortunately, Gauteng's academic institutions and hospitals have not leveraged these funding opportunities or addressed the backlog issues in surgery and radiation. One recent positive development is that some brachytherapy is now available, which provides an opportunity for patients diagnosed with early-stage prostate cancer to have treatment. In response to the stagnation in government action, the Cancer Alliance led a court case against the Gauteng Department of Health (GDoH) in July 2024. CASE NO. 2024-071038. The aims of this case include: Why the Cancer Alliance has launched a court case against the Gauteng Department of Health,for their failure to provide timeous radiation oncology services to cancer patients at Charlotte Maxeke Hospital Salomé Meyer BA(SW) Pret. BA (Medical Social Work) Hons (US). M.Soc Sci (UCT). Salome is the chairperson of the Cancer Alliance EXCO Committee, has been actively involved in the organisation since its inception in 2011. As an independent cancer advocate, she was instrumental in the development of the breast cancer policy in 2017. She took on an activist role when she joined the Fix the Patent Law campaign in 2017 as the Access to Medicine Project Manager and successfully leveraged and advocated for trastuzumab and lenalidomide to be added to the Essential Medicines List of the National Department of Health. Salomé serves on the Unitaid NGO Delegation for Cervical Cancer, the Medicines Patent Pool Community Advisory Panel for Cancer, We CAN Africa (Women's Empowerment Cancer Advocacy Network) and the newly established African Cervical Health Alliance (ACHA) as a Steering Committee member.
21 Urgent Relief Sought (Part A): • An update and reassessment of the backlog list within 45 days. • Immediate initiation of radiation oncology treatments for patients. • A temporary restraint on the R250 million allocated for planning services pending a judicial review under Part B. • A declaration that the GDoH's failure to provide timely treatment is unlawful and infringes on constitutional rights. The Cancer Alliance is represented by SECTION27, with Khanyisa Mapipa, Head of the Health Rights Programme, serving as the attorney. Senior Counsel includes Advocate Lerato Zikalala and Advocate Faatima Mohamed. This case is scheduled to be heard on 21st November 2024, by Judge Janse Van Nieuwenhuizen. About the Cancer Alliance The Cancer Alliance is a collective group of cancer control non-prot organisations and cancer advocates brought together under a common mandate, to provide a platform of collaboration for cancer civil society to speak with one voice and be a powerful tool to affect change for all South African adults and children affected by cancer. www.canceralliance.org.za UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
22 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE In many rst world, high-income countries there is a problem with the overdiagnosis and overtreatment of prostate cancer.1 In South Africa, as with many low- and middle-income countries, the majority of men are reliant on public health facilities where the problem is one of underdiagnosis and under treatment.1 Inadequate availability of and insufcient access to screening have resulted in high rates of men presenting with locally advanced or advanced disease at public health facilities.2,3 The problem is further exacerbated by a lack of Department of Health guidelines or policies on prostate cancer for the public sector. The result is that many primary care public clinics will not screen men for prostate cancer unless they present with symptoms. Given that there are usually no symptoms of prostate cancer in the early stages, this in effect means that patients are expected to wait until they have incurable prostate cancer before they seek help. In an effort to address the underdiagnosis of prostate cancer, The Prostate Cancer Foundation has been partnering with its member companies to make screening more accessible to men. The rst initiative for the year was a PSA testing campaign run in collaboration with Astellas Pharma at various private healthcare facilities around South Africa. Additional campaigns funded by Accord Healthcare and RMB will be conducted in the coming months. “Making screening more accessible is the only way to decrease the number of men presenting with de nova metastatic prostate cancer at our public sector health facilities,” says Prostate Cancer Foundation CEO, Andrew Oberholzer. The Prostate Cancer Foundation and Astellas team up to make prostate cancer screening more accessible for South African men Astellas CEO Barnaby McKay with the oncology brand manager Nicola Scott (R) and sales representative Tanya Wielsma (L) at The Urology Hospital test site Prostate Cancer Foundation's professional nurse Sr Marilyn van der Berg making sure that patients understand the advantages and disadvantages of PSA screening before consenting to a PSA test
23 Lancet Laboratories did the PSA tests Prostate Cancer Foundation's Chairman Dr Lance Coetzee with Astellas sales representative Tanya Wielsma References 1 James ND, Tannock I, J N'Dow, The Lancet Commission on prostate cancer: planning for the surge in cases. www.thelancet.com. Published online April 4, 2024. https://doi.org/10.1016/S01406736(24)00651-21 2 Benedict MOA, Steinberg WJ, Claasen F, et al. The prole of Black South African men diagnosed with prostate cancer in the Free State, South Africa. S Afr Fam Pract (2004). 2023 Jan 10;65(1). 3 Le Roux HA, Urry RJ, Sartorius B et al. Prostate Cancer at a regional hospital in South Africa: we are only seeing the tip of the iceberg. South African Journal of surgery. 01 Dec 2015, 53(3 and 4):57-62 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
24 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Dear Healthcare Professional, ® Adcock Ingram is pleased to announce the launch of SWIFSUL , a combination of 0,5 mg dutasteride and 0,4 mg tamsulosin hydrochloride, indicated for the treatment of moderate to 1,2 severe symptoms of benign prostatic hyperplasia (BPH). ® SWIFSUL takes the pressure off BPH, offering patients: 3 • Rapid and durable symptom relief • A reduction in the long-term risk of BPH progression • A reduction in the risk of acute urinary retention • A reduction in BPH-related surgery vs. monotherapy • A convenient once-daily oral dose ® 1 SWIFSUL is the affordable Benign Prostatic Hyperplasia treatment choice. ® SWIFSUL an Adcock Ingram generic offering a R 265.87 saving# vs. the originator, providing greater 1 access to more affordable treatment for BPH. ® 4 SWIFSUL is available from leading pharmacies and wholesalers in packs of 30's. References: 1. Generics dictionary March 2024. Available from www.generic.co.za. Accessed July 2024. ® 2. SWIFSUL professional information, August 2023. 3. Roehrborn CG, Siami P, Barkin J, et al. The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study. Eur Eurol 2010;57:123–131. 4. Pricing File, March 2024. ® S4 SWIFSUL 0,5 mg/0,4 mg hard gelatine capsules. Each hard gelatine capsule contains 0,5 mg dutasteride and 0,4 mg tamsulosin hydrochloride (equivalent to 0,367 mg tamsulosin). Reg. No. 55/21.12/0032. For full prescribing information refer to professional information approved by SAHPRA (August 2023). Applicant & Marketed by: Adcock Ingram Limited. Co. Reg. No. 1949/034385/06, Private Bag X69, Bryanston, 2021, South Africa. Customer Care: 0860 ADCOCK / 232625. www.adcock.com. 202408161017736 August 2024 SWIFSUL® PRESS RELEASE
25 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
26 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Summary South Africa is facing an impending crisis as regards cancer prevention and control. The Percept Report predicts that with escalating cancer incidence in South Africa, an additional R50 billion will be needed by 2030 to mount an effective public health response. However, given inadequate state funding to meet these demands together with poor coordination of services, geographic disparities and public vs private inequities, it is highly unlikely that the country will be able to full its human rights obligations to cancer patients. It is against this backdrop of burgeoning need, that we investigated legal responses to similar challenges in six other countries with national cancer acts (NCAs). Although there are differences between these NCAs, the United Kingdom (UK), the United States of America (USA), Japan, Kenya, the Philippines and Chile share similar approaches to: developing a national cancer plan; establishing a national cancer prevention and control coordinating body; nancing cancer care and research; ensuring social protections; achieving equitable services; improving cancer surveillance; and instituting accountability mechanisms. Given the urgency to solve South Africa s current health policy decits regarding cancer, we suggest key lessons that could be leveraged to generate legislative reform. Policy conclusions • To address cancer prevention, control, care, palliation and research in a comprehensive manner, countries around the world have successfully implemented NCAs to coordinate resources and ensure accountability; • Options for South Africa would be to follow suit, and develop our own dedicated NCA, or to amend existing legislation to achieve more equitable outcomes for cancer diagnosis and treatment, as well as institute social protections for people living with cancer; • While a systematic review of gaps in existing legal frameworks is required, obvious legislation open to such amendments are: the National Health Insurance Bill [B11-2019] and the Conditions of Basic Employment Act [No 75 of 1997]. • Key stakeholders from government, health professionals, civil society and the private sector are called upon to initiate a national debate on how best to address the legislative and policy gaps in our current cancer frameworks. CLOSING THE GAPS IN CANCER PREVENTION AND CONTROL: IS A NATIONAL CANCER ACT THE SOLUTION FOR SOUTH AFRICA?
RkJQdWJsaXNoZXIy NTIyOTQ=