2. UroToday Home
  3. Library Resources
  4. Kidney Cancer Today

Library Resources

Habits That Can Affect Your Bladder

Common Bladder Irritants Found in Foods and Drinks

Certain foods, liquids and beverages, medications and even herbs can “trigger” your bladder symptoms. Their effect on the bladder is not always understood and the same food or liquid may affect different people and their bladders in different ways. Check the lists found here to see if any of them are adding to your symptoms. If you find one, stop them for a few days to see if your bladder symptoms improve. Then introduce it back and see if you notice any changes.

Artificial Intelligence and Prostate Cancer: Diagnosis and Grading, mpMRI, and Active Surveillance

Across all aspects of daily life, artificial intelligence more than ever is harnessing the power of machine learning to automate and improve the efficiency of tasks. This is also true in medicine and, in particular, in the field of prostate cancer. The concept of artificial intelligence began in the 1950s with the prime objective of emulating the cognitive capabilities of human beings in machines. More specifically, artificial intelligence is the ability of a machine to independently replicate intellectual processes typical of human cognition. Machine learning comprises algorithms that parse data, learn from that data, and then apply what they have learned to make informed decisions. Deep learning is a form of machine learning that is inspired by the structure of the human brain and is particularly effective in feature detection:1

Written by: Zachary Klaassen, MD MSc & Rashid K. Sayyid, MD MSc
References:
  1. George RS, Htoo A, Cheng M, et al. Artificial intelligence in prostate cancer: Definitions, current research, and future directions. Urol Oncol. 2022;40: 262-270.
  2. Marginean F, Arvidsson I, Simoulis A, et al. An Artificial Intelligence-based Support Tool for Automation and Standardisation of Gleason Grading in Prostate Biopsies. Eur Urol Focus. 2021;7: 995-1001.
  3. Huang W, Randhawa R, Jain P, et al. Development and Validation of an Artificial Intelligence-Powered Platform for Prostate Cancer Grading and Quantification. JAMA Netw Open. 2021;4: e2132554.
  4. Bulten W, Kartasalo K, Chen PC, et al. Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge. Nat Med. 2022;28: 154-163.
  5. Paulson N, Zeevi T, Papademetris M, et al. Prediction of Adverse Pathology at Radical Prostatectomy in Grade Group 2 and 3 Prostate Biopsies Using Machine Learning. JCO Clin Cancer Inform. 2022;6: e2200016.
  6. Kartasalo K, Bulten W, Delahunt B, et al. Artificial Intelligence for Diagnosis and Gleason Grading of Prostate Cancer in Biopsies-Current Status and Next Steps. Eur Urol Focus. 2021;7: 687-691.
  7. Jung M, Jin MS, Kim C, et al. Artificial intelligence system shows performance at the level of uropathologists for the detection and grading of prostate cancer in core needle biopsy: an independent external validation study. Mod Pathol. 2022;35: 1449-1457.
  8. Suarez-Ibarrola R, Sigle A, Eklund M, et al. Artificial Intelligence in Magnetic Resonance Imaging-based Prostate Cancer Diagnosis: Where Do We Stand in 2021? Eur Urol Focus. 2022;8: 409-417.
  9. Mehralivand S, Harmon SA, Shih JH, et al. Multicenter Multireader Evaluation of an Artificial Intelligence-Based Attention Mapping System for the Detection of Prostate Cancer With Multiparametric MRI. AJR Am J Roentgenol. 2020;215: 903-912.
  10. Hiremath A, Shiradkar R, Fu P, et al. An integrated nomogram combining deep learning, Prostate Imaging-Reporting and Data System (PI-RADS) scoring, and clinical variables for identification of clinically significant prostate cancer on biparametric MRI: a retrospective multicentre study. Lancet Digit Health. 2021;3: e445-e454.
  11. Hosseinzadeh M, Saha A, Brand P, Slootweg I, de Rooij M, Huisman H. Deep learning-assisted prostate cancer detection on bi-parametric MRI: minimum training data size requirements and effect of prior knowledge. Eur Radiol. 2022;32: 2224-2234.
  12. Lee C, Light A, Saveliev ES, van der Schaar M, Gnanapragasam VJ. Developing machine learning algorithms for dynamic estimation of progression during active surveillance for prostate cancer. NPJ Digit Med. 2022;5: 110.
  13. Nayan M, Salari K, Bozzo A, et al. A machine learning approach to predict progression on active surveillance for prostate cancer. Urol Oncol. 2022;40: 161 e161-161 e167.

How to Do Pelvic Floor Muscle Exercises

WHAT ARE THE PELVIC FLOOR MUSCLES?
Your pelvic floor muscles provide support to your bladder, and rectum and, in women, the vagina and the uterus. These muscles are like a sling or hammock in the bottom of your pelvis which is why they are called pelvic floor muscles. If they weaken or are damaged, they do not support pelvic organs and may cause bladder control problems. Keeping the muscles strong by training them, can help prevent urine leakage. You can make these muscles stronger by doing exercises (often called Kegel exercises).

The Impact of Surgeon Experience and Volume on Patient Outcomes in Radical Prostatectomy Patients

Introduction

The last decade has seen an increased uptake of the robotic-assisted laparoscopic approach for radical prostatectomies. Despite the negative results of the only published phase III randomized clinical trial comparing robotic-assisted laparoscopic to open radical prostatectomy, which demonstrated no significant differences in short- and medium-term functional outcomes between the two approaches,1 it is currently estimated that more than 70% of radical prostatectomy surgeries performed since 2012 in the United States have been with robotic assistance.2 In 2018, it was estimated that 92.6% of all radical prostatectomies in England were performed using this minimally invasive technique.3
Written by: Rashid K. Sayyid, MD MSc and Zachary Klaassen, MD,MSc
References:
  1. Coughlin GD, Yaxley JW, Chambers SK, et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study. Lancet Oncol 2018;19(8):1051-1060.
  2. Schroeck FR, Jacobs BL, Bhayani  SB, et al.  J.  Cost of new technologies in prostate cancer treatment: systematic review of costs and cost effectiveness of robotic-assisted laparoscopic prostatectomy, intensity-modulated radiotherapy, and proton beam therapy. Eur Urol 2017;72(5):712-735.
  3. Gray WK, Day J, Briggs TWR, Harrison S. An observational study of volume–outcome effects for robot-assisted radical prostatectomy in England. BJU International 2021;12(1):93-103.
  4. Begg CB, Riedel ER, Bach PB, et al. Variations in Morbidity after Radical Prostatectomy. N Engl J Med 2002;346:1138-1144.
  5. Hu JC, Gold KF, Pashos CL, et al. Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol 2003;21(3):401-405.
  6. Almatar A, Wallis CJD, Hrrschorn S, et al. Effect of radical prostatectomy surgeon volume on complication rates from a large population-based cohort. Can Urol Assoc J 2016;10(1-2):45-49.
  7. Godtman RA, Persson E, Cazzaniga W, et al. Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study. PLoS One 2021;16(6):e0253081.
  8. Gray WK, Day J, Briggs TWR, Harrison S. An observational study of volume–outcome effects for robot-assisted radical prostatectomy in England. BJU International 2021;129(1):93-103.
  9. Van den Broeck T, Oprea-Lager D, Moris L, et al. A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer. Eur Urol 2021;80(5):531-545.
  10. Porcaro AB, Tafuri A, Sebben M, et al. Linear extent of positive surgical margin impacts biochemical recurrence after robotassisted radical prostatectomy in a high-volume centre. J Robot Surg 2020;14:663–675.
  11. Steinsvik EAS, Axcrona K, Angelsen A, et al. Does a surgeon’s annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up?—Findings from a prospective national study. Scand J Urol 2013;47:92–100.
  12. Williams SB, Gu X, Lipsitz SR, Nguyen PL, Choueiri TK, Hu JC. Utilization and expense of adjuvant cancer therapies following radical prostatectomy. Cancer 2011;117:4846–54.
  13. Hu JC, Wang Q, Pashos CL, Lipsitz SR, Keating NL. Utilization and outcomes of minimally invasive radical prostatectomy. J Clin Oncol 2008;26:2278–84.
  14. Bolton DM, Papa N, Ta AD, et al. Predictors of prostate cancer specific mortality after radical prostatectomy: 10 year oncologic outcomes from the Victorian Radical Prostatectomy Registry. BJU Int 2015;116:66–72.
  15. Schmitges J, Trinh QD, Sun M, et al. Annual prostatectomy volume is related to rectal laceration rate after radical prostatectomy. Urology 2012;79:796–803.
  16. Sharma V, Meeks JJ. Open conversion during minimally invasive radical prostatectomy: impact on perioperative complications and predictors from national data. J Urol 2014;192:1657–1662.
  17. Begg CB, Riedel ER, Bach PB, et al. Variations in morbidity after radical prostatectomy. N Engl J Med 2002;346:1138–1144.
  18. Leow JJ, Leong EK, Serrell EC, et al. Systematic Review of the Volume-Outcome Relationship for Radical Prostatectomy. Eur Urol Focus 2018;4(6):775-89.
  19. Bravi CA, Tin A, Vertosick E, et al. The Impact of Experience on the Risk of Surgical Margins and Biochemical Recurrence after Robot-Assisted Radical Prostatectomy: A Learning Curve Study. J Urol 2019;202(1):108-113.
  20. Klein EA, Bianco FJ, Serio AM, et al. Surgeon Experience is Strongly Associated with Biochemical Recurrence after Radical Prostatectomy for all Preoperative Risk Categories. J Urol 2008;179(6):2212-2216.
  21. Alemozaffar M, Duclos A, Hevelone ND, et al. Technical Refinement and Learning Curve for Attenuating Neurapraxia During Robotic-Assisted Radical Prostatectomy to Improve Sexual Function. Eur Urol 2012;61(6):1222-12228.
  22. Ju IE, Trieu D, Chang SB, et al. Surgeon Experience and Erectile Function After Radical Prostatectomy: A Systematic Review. Sex Med Rev 2021;9(4):650-658.
  23. Fossati N, Di Trapani E, Gandaglia G, et al. Assessing the Impact of Surgeon Experience on Urinary Continence Recovery After Robot-Assisted Radical Prostatectomy: Results of Four High-Volume Surgeons. J Endourol 2017;31(9):872-877.
  24. Matulewicz RS, Tosoian JT, Stimson CJ, et al. Implementation of a Surgeon-Level Comparative Quality Performance Review to Improve Positive Surgical Margin Rates during Radical Prostatectomy. J Urol 2017;197(5):1245-1250.
  25. Kumar RV, Fergusson DA, Lavallee, et al. Performance Feedback May Not Improve Radical Prostatectomy Outcomes: The Surgical Report Card (SuRep) Study. J Urol 2021;206(2):346-353.

Controlling Your Bladder Urges With Bladder Training

Usually, the bladder can hold urine for 4 to 5 hours, then you feel the urge to pee (urinate) and you should be able to walk to the bathroom. But some people will have an overactive bladder and feel a sudden urge to pee that comes on quickly, they may have that “gotta-go” sensation. This is called bladder urgency.

The Current Landscape of Neoadjuvant Chemotherapy in Cisplatin Eligible Patients with Clinically Localized, Muscle Invasive Bladder Cancer

Introduction

Bladder cancer is currently the 10th most commonly diagnosed malignancy worldwide, with an estimated 110,500 men and 70,000 women diagnosed annually.1 While the majority of patients are diagnosed with non-muscle invasive disease (i.e. carcinoma in situ, Ta, and T1), approximately 25 to 33% of patients are initially diagnosed with muscle invasive bladder cancer and a meaningful proportion of patients initially diagnosed with non-muscle invasive disease will subsequently progress to MIBC.1

Written by: Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
References:
  1. Burger M, Catto JWF, Dalbagni G, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol 2013;63(2):234-41.
  2. Flaig TW, Speiss PE, Abern M, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw 2022;20(8):866-878.
  3. EAU Guidelines: Muscle-invasive and Metastatic Bladder Cancer. Accessed: December 27, 2022.
  4. ASCO Cancer.Net: Bladder Cancer – Statistics. Accessed: December 27, 2022.
  5. Martinez-Pineiro JA, Martin MG, Arovena F, et al. Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study. J Urol 1995;153(3 Pt 2):964-73.
  6. Rintala E, Hannisdahl E, Fossa SD, et al. Neoadjuvant chemotherapy in bladder cancer: a randomized study. Nordic Cystectomy Trial I. Scand J Urol Nephrol 1993;27(3):355-62.
  7. Malmstrom PU, Rintala E, Wahlqvist R, et al. Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group. J Urol 1996;155(6):1903-6.
  8. Sherif A, Rintala E, Mestad O, et al. Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2. Scand J Urol Nephrol 2022;36(6):419-25.
  9. International collaboration of trialists on behalf of the Medical Research Council Advanced Bladder Cancer Working Party, et al. Neoadjuvant cisplatin,methotrexate,and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet 1999;354(9178):533-40.
  10. International Collaboration of Trialists, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011;29(16):2171-7.
  11. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-66.
  12. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003;361(9373):1927-34.
  13. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48(2):202-5.
  14. Kitamura H, Tsukamoto T, Shibata T, et al. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol 2014;25(6):1192-8.
  15. Dash A, Pettus JA, Herr H, et al. A Role for Neoadjuvant Gemcitabine Plus Cisplatin in Muscle-Invasive Urothelial Carcinoma of the Bladder: A Retrospective Experience. Cancer 2008;113(9):2471-7.
  16. Goel S, Sinha EJ, Bhaskar V, et al. Role of gemcitabine and cisplatin as neoadjuvant chemotherapy in muscle invasive bladder cancer: Experience over the last decade. Asian J Urol 2019;6(3):222-9.
  17. Iyer G, Tully CM, Zabor EC, et al. Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience. Clin Genitourin Cancer 2020;18(5):387-94.
  18. Osman MA, Gabr AM, Elkady MS. Neoadjuvant chemotherapy versus cystectomy in management of stages II, and III urinary bladder cancer. Arch Ital Urol Androl 2014;86(4):278-83.
  19. Yafi FA, Aprikian AG, Chin JL, et al. Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience. BJU Int 2011;108(4):539-45.
  20. Pfister C, Gravis G, Flechon A, et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses. Eur Urol 2021;29(2):214-21.
  21. Pfister C, Gravis G, Flechon A, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol 2022;40(18):2013-22.

 

 

 

PARP Inhibitor Plus Androgen Receptor Signaling Inhibitor Combinations: Will This Be The Future of mCRPC First-Line Therapy?

Introduction: Despite the approval of numerous agents in this setting, patients with metastatic castrate-resistant prostate cancer (mCRPC) have a poor prognosis, with an estimated median overall survival (OS) of approximately three years with currently approved first-line agents.1-3

Written by: Rashid K. Sayyid, MD MSc & Zachary Klaassen, MD MSc
References:
  1. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368(2):138-48.
  2. Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur Urol 2017; 71(2):1 51-4.
  3. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351(15):1502-12.
  4. George DJ, Sartor O, Miller K, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clin Genitourin Cancer 2020; 18(4):284-94.
  5. De Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 382(22): 2091-102.
  6. Abida W, Patnaik A, Campbell D, et al. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol 2020; 38(32): 3763-72.
  7. Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or Physician’s Choice in Metastatic Prostate Cancer. N Engl J Med 2023; 388: 719-32.
  8. Asim M, Tarish F, Zecchini HI, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun 2017; 8: 374.
  9. Schiewer MJ, Goodwin JF, Han S, et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov 2012; 2: 1134-49.
  10. Li L, Karanika S, Yang G, et al. Androgen receptor inhibitor-induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer. Sci Signal 2017; 10: eaam7479.
  11. Clarke N, Wiechno P, Alekseev B, et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 2018; 19: 975-86.
  12. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2022; 1(9).
  13. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Final overall survival (OS) in PROpel: abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 2023; 41(Suppl 6; abstr LBA16).
  14. Chi KN, Rathkopf DE, Smith MR, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 2023; JCO2201649.
  15. Agarwal N, Azad A, Carles J, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 2023; 41 (Suppl 6; abstr LBA17).

The Current Landscape of Neoadjuvant Chemotherapy/Immunotherapy Combinations in Patients with Clinically Localized, Muscle Invasive Bladder Cancer

Introduction

Bladder cancer is currently the 10th most commonly diagnosed malignancy worldwide. It is estimated that approximately 110,500 men and 70,000 women are annually diagnosed with bladder cancer worldwide.1 While the majority of patients are initially diagnosed with non-muscle invasive disease (i.e. carcinoma in situ, Ta, and T1), approximately 25 to 33% of patients are diagnosed with muscle invasive bladder cancer and a meaningful proportion of patients initially diagnosed with non-muscle invasive disease will subsequently progress to MIBC.1

Written by: Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
References:

References

  1. Burger M, Catto JWF, Dalbagni G, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol 2013;63(2):234-41.
  2. Flaig TW, Speiss PE, Abern M, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw 2022;20(8):866-878.
  3. EAU Guidelines: Muscle-invasive and Metastatic Bladder Cancer.  Accessed: December 27, 2022.
  4. ASCO Cancer.Net: Bladder Cancer – Statistics. Accessed: December 27, 2022.
  5. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48(2):202-5.
  6. Pfister C, Gravis G, Flechon A, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol 2022;40(18):2013-22.
  7. Rhea LP, Mendez-Marti S, Kim D, Aragon-Chin JB. Role of immunotherapy in bladder cancer. Cancer Treat Res Commun 2021;26:100296.
  8. Rose TL, Harrison MR, Deal AM, et al. Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol 2021;39(28):3140-8.
  9. Funt SA, Lattanzi M, Whiting K, et al. Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial. J Clin Oncol 2022;40(12):1312-22.

Suprapubic (SP) Urinary Catheter (SPC or SP Tube [SPT])

Background: Suprapubic catheterization (SPC) is placement of a hollow tube, a urinary catheter, into the bladder through a small incision in the avascular midline of the rectus sheath in the lower abdominal wall just above (3 cm) the symphysis of the pubic bone and below the naval. These 2 Figures show an SPC inserted in a female and a male. Like an indwelling urethral catheter (IUC), the catheter is there to drain the bladder and is secured in the bladder by a balloon inflated with fluid.
Written by: Diane K. Newman, DNP, ANP-BC, FAAN

Radiotherapy in Prostate Cancer: Utilization of Adjuvant and Salvage Radiotherapy

Introduction

While external beam radiotherapy is a standard treatment option as first-line therapy for men with localized prostate cancer, it is also an important component of care for patients following radical prostatectomy. For approximately two-thirds of patients undergoing radical prostatectomy for prostate cancer, surgery is curative, and patients remain disease-free (without biochemical or radiographic evidence of recurrence).1 However, patients with adverse pathologic findings (defined as seminal vesicle invasion, extraprostatic extension, and positive surgical margins (residual tumor at the surgical site) experience up to a 60% risk of recurrence at 10 years.2
Written by: Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
References:
  1. Bianco Jr FJ, Scardino PT, Eastham JA. Radical prostatectomy: long-term cancer control and recovery of sexual and urinary function ("trifecta"). Urology. 2005;66(5 Suppl):83-94.
  2. Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol. 2013;190(2):441-9.
  3. Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020;396(10260):1413-1421.
  4. Kneebone A, Fraser-Browne C, Duchesne GM, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020;21(10):1331-1340.
  5. Sargos P, Chabaud S, Latorzeff I, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1341-1352.
  6. Vale CL, Fisher D, Kneebone A, et al. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020;396(10260):1422-1431.
  7. Pollack A, Karrison TG, Balogh A, et al. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet.2022;399(10338):1886-1901.
  8. Feng FY, Huang H, Spratt DE, et al. Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial. JAMA Oncol. 2021;7(4):544-552.
  9. Dal Pra A, Ghadjar P, Hayoz S, et al. Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial. Ann Oncol. 2022;33(9):950-958.
  10. Jani AB, Schreibmann E, Goyal S, et al. 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial. 2021;397(10288):1895-1904.

Urinary Catheter Valves

Description: A urinary catheter valve, sometimes referred to as a “catheter plug” is a tap-like device fitted into the end of an indwelling urethral catheter (IUC) or suprapubic catheter (SPC). It allows the bladder to fill and then be emptied into a toilet or container at regular intervals during the day (e.g. 4-5 times/day). This mimics the physiologic function of the bladder. A catheter valve may be used in those patients who may have other options for future bladder management,
Written by: Diane K. Newman, DNP, ANP-BC, FAAN

The Current Landscape of Neoadjuvant Immunotherapy Agent Combinations in Patients with Clinically Localized, Muscle Invasive Bladder Cancer

Introduction

Bladder cancer is currently the 10th most commonly diagnosed malignancy worldwide. It is estimated that approximately 110,500 men and 70,000 women are annually diagnosed with bladder cancer worldwide.1 While the majority of patients are diagnosed with non-muscle invasive disease (i.e. carcinoma in situ, Ta, and T1), approximately 25 to 33% of patients are initially diagnosed with muscle-invasive bladder cancer and a meaningful proportion of patients initially diagnosed with non-muscle invasive disease will subsequently progress to MIBC.1

Written by: Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
References:
  1. Burger M, Catto JWF, Dalbagni G, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol 2013;63(2):234-41.
  2. Flaig TW, Speiss PE, Abern M, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw 2022;20(8):866-878.
  3. EAU Guidelines: Muscle-invasive and Metastatic Bladder Cancer. Accessed: December 27, 2022.
  4. ASCO Cancer.Net: Bladder Cancer – Statistics. Accessed: December 27, 2022.
  5. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48(2):202-5.
  6. Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011;12: 211–4.
  7. Rhea LP, Mendez-Marti S, Kim D, Aragon-Chin JB. Role of immunotherapy in bladder cancer. Cancer Treat Res Commun 2021;26:100296.
  8. Pfister C, Gravis G, Flechon A, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol 2022;40(18):2013-22.
  9. Van Dijk N, Gil-Jimenez A, Silina K, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med 2020;26(12):1839-44.
  10. Danaher P, Warren S, Lu R, et al. Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA).J Immunother Cancer 2018;6(1):63.a
  11. Gao J, Navai N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med 2020;26(12):1845-51.
  12. Li R, Steinberg GD, Uchio EM, et al. CORE1: Phase 2, single-arm study of CG0070 combined with pembrolizumab in patients with nonmuscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guerin (BCG). J Clin Oncol 2022; 2022 ASCO Annual Meeting I.

Suprapubic Urinary Catheter Indications

Suprapubic catheters are often placed for a short time following certain surgical procedures as they can contribute to patients’ improved recovery times, compared with urethral catheterization. They can provide stable bladder drainage before and after complex urethral reconstructions.
Written by: Diane K. Newman, DNP, ANP-BC, FAAN

The Current Landscape of Neoadjuvant Single Agent Therapy in Patients with Cisplatin Ineligible Clinically Localized, Muscle Invasive Bladder Cancer

Introduction

Bladder cancer is currently the 10th most commonly diagnosed malignancy worldwide. It is estimated that approximately 110,500 men and 70,000 women are annually diagnosed with bladder cancer globally.1 While the majority of patients are diagnosed with non-muscle invasive disease (i.e. carcinoma in situ, Ta, and T1), approximately 25 to 33% of patients are initially diagnosed with muscle invasive bladder cancer and a meaningful proportion of patients initially diagnosed with non-muscle invasive disease will subsequently progress to MIBC.1

Written by: Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
References:
  1. Burger M, Catto JWF, Dalbagni G, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol 2013;63(2):234-41.
  2. Flaig TW, Speiss PE, Abern M, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw 2022;20(8):866-878.
  3. EAU Guidelines: Muscle-invasive and Metastatic Bladder Cancer. Accessed: December 27, 2022.
  4. ASCO Cancer.Net: Bladder Cancer – Statistics. Accessed: December 27, 2022.
  5. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48(2):202-5.
  6. Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011;12: 211–4.
  7. Rhea LP, Mendez-Marti S, Kim D, Aragon-Chin JB. Role of immunotherapy in bladder cancer. Cancer Treat Res Commun 2021;26:100296.
  8. Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018;36(34):3353-60.
  9. Basile G, Banidin M, Gibb EA, et al. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res 2022;28(23):5107-14.
  10. Powles T, Kockx M, Rodriguez-Vida, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med 2019; 25(11):1706-14.
  11. Pfister C, Gravis G, Flechon A, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol 2022;40(18):2013-22.
  12. Yu EY, Petrylak DP, O’Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 May 12;S1470-2045(21)00094-2.
  13. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021 Mar 25;384(12):1125-35.

Suprapubic Catheterization (SPC)-Related Complications and Problems

The complication rate for cystostomy (surgical procedure for insertion of a suprapubic catheter (SPC)) ranges from 1.6% to 2.4%. The first few catheter changes after the initial SPC insertion should be performed using a guidewire as acute complications can occur.
Written by: Diane K. Newman, DNP, ANP-BC, FAAN

The Current Landscape of Neoadjuvant Therapy in Patients with Upper Tract Urothelial Carcinoma

Introduction

Urothelial carcinoma of the upper tract accounts for only five to ten percent of all urothelial carcinomas,1 with an estimated annual incidence in Western countries of almost two cases per 100,000 inhabitants.2 Approximately two-thirds of patients with de novo upper tract urothelial carcinoma present with invasive disease at diagnosis,3 likely owing to the absence of a muscularis propria layer in the upper tracts. Large series have reported five-year cancer-specific mortality rates of 30% for muscle-invasive, organ-confined tumors and 56% for locally advanced tumors.4

Written by: Rashid K. Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
References:
  1. Babjuk, M, Burger M, Capoun O, et al. EAU Guidelines on Non-muscle-invasive Bladder Cancer (T1, T1 and CIS), in EAU Guidelines, Edn. presented at the 37th EAU Annual Congress Amsterdam. 2022, EAU Guidelines Office, Arnhem, The Netherlands.
  2. Siegel, RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin 2021;71(1):7-33.
  3. Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer 2009;115(6):1224-33.
  4. van Doeveren T, van der Mark M, van Leeuwen PJ, et al. Rising incidence rates and unaltered survival rates for primary upper urinary tract urothelial carcinoma: a Dutch population-based study from 1993 to 2017. BJU Int 2021; 128(3): 343-51.
  5. Collà Ruvolo C, Nocera L, Stolzenbach LF, et al.. Tumor Size Predicts Muscle-invasive and Non-organ-confined Disease in Upper Tract Urothelial Carcinoma at Radical Nephroureterectomy. Eur Urol Focus 2022;8(2):498-505.
  6. Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet 2020;395(10232):1268-77.
  7. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48(2):202-5.
  8. Hoffman-Censits JH, Trabulsi EJ, Chen DYT, et al. Neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) in patients with high-grade upper-tract urothelial carcinoma. J Clin Oncol 2014;32(4):Suppl.
  9. Margulis V, Puligandla M, Trabulsi EJ, et al. Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients with High Grade Upper Tract Urothelial Carcinoma. J Urol 2020;203(4):690-8.
  10. Coleman JA, Yip W, Wong NC, et al. Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma. J Clin Oncol 2023;JCO2200763.
  11. Basile G, Banidin M, Gibb EA, et al. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res 2022;28(23):5107-14.

Procedure for Changing a Suprapubic Catheter (SPC or SPT)

The initial insertion of a suprapubic catheter (SPC), a procedure referred to as a suprapubic cystostomy, can be performed under local or general anesthesia with a trocar system, using cystoscopic or ultrasound guidance. SPC insertion is an aseptic procedure that can be performed in an outpatient or office setting
Written by: Diane K. Newman, DNP, ANP-BC, FAAN

Treatment Intensification in Metastatic Hormone Sensitive Prostate Cancer (mHSPC): Metachronous Low Volume mHSPC

Since 2015, multiple combination treatment strategies have emerged for the management of patients with metastatic hormone sensitive prostate cancer (mHSPC). The addition of docetaxel and/or androgen receptor-axis targeted (ARAT) agents to standard androgen deprivation therapy (ADT), in the form of doublet and triplet treatment strategies, has demonstrated overall survival benefits in this cohort of patients. As such, these drug combinations have changed the standard of care approaches in these men.1
Written by: Rashid K. Sayyid, MD MSc and Zachary Klaassen, MD MSc
References:
  1. Weiner AB, Siebert AL, Fenton SE, et al. First-line Systemic Treatment of Recurrent Prostate Cancer After Primary or Salvage Local Therapy: A Systematic Review of the Literature. Eur Urol Oncol. 2022.
  2. Cancer Stat Facts: Prostate Cancer. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/prost.html. Accessed: Nov 14, 2022
  3. Deek MP, Van der Eecken K, Phillips R, et al. The mutational landscape of metastatic castration-sensitive prostate cancer: the spectrum theory revisited. Eur Urol. 2021;80:632-640
  4. Stopsack KH, Nandakumar S, Wimber AG, et al. Oncogenic genomic alterations, clinical phenotypes, and outcomes in metastatic castration-sensitive prostate cancer. Clin Cancer Res. 2020;26:3230-3238.
  5. Sweeney CJ, Chen Y, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N ENgl J Med. 2015;373:737-746.
  6. Fizai K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2022;399(10336):1695-1707.
  7. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022;386(12):1132-1142.
  8. Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121-131.
  9. Hoyle AP, Ali A, James ND, et al. Abiraterone in “High-” and “Low-risk” Metastatic Hormone-sensitive Prostate Cancer. Eur Urol. 2018;76(6):719-728.
  10. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377:338-351.
  11. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021;39(2):2294-2303.
  12. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986.
  13. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366.
  14. Boeve LMS, Hulshof MCCM, Vis AN, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019;75(3):410-418.
  15. Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446-453.
  16. Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020;6(5):650-659.
  17. Deek MP, van der Eecken K, Sutera P, et al. Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials. J Clin Oncol. 2022;JCO2200644.
  18. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058.

Artificial Intelligence and Prostate Cancer: Risk Stratification After Primary Therapy, ADT Treatment Intensification, and Evaluation of Metastatic Disease

Artificial intelligence continues to transform the field of medicine, including the management of prostate cancer. In this Center of Excellence article, we discuss the contemporary literature evaluating artificial intelligence for risk stratification after primary therapy, ADT treatment intensification, and evaluation of metastatic disease.

Written by: Zachary Klaassen, MD, MSc and Rashid K. Sayyid, MD, MSc
References:
  1. Tan YG, Fang AHS, Lim JKS, et al. Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy. Prostate. 2022;82: 298-305.
  2. McIntosh C, Conroy L, Tjong MC, et al. Clinical integration of machine learning for curative-intent radiation treatment of patients with prostate cancer. Nat Med. 2021;27: 999-1005.
  3. Esteva A, Feng J, van der Wal D, et al. Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials. NPJ Digit Med. 2022;5: 71.
  4. Yang R, Zhu D, Howard LE, et al. Identification of Patients With Metastatic Prostate Cancer With Natural Language Processing and Machine Learning. JCO Clin Cancer Inform. 2022;6: e2100071.
  5. Elledge CR, LaVigne AW, Fiksel J, et al. External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases. JCO Clin Cancer Inform. 2021;5: 304-314.
  6. Kartasalo K, Bulten W, Delahunt B, et al. Artificial Intelligence for Diagnosis and Gleason Grading of Prostate Cancer in Biopsies-Current Status and Next Steps. Eur Urol Focus. 2021;7: 687-691.

Treatment Intensification in Metastatic Hormone Sensitive Prostate Cancer (mHSPC): Metachronous High Volume mHSPC

Since 2015, multiple combination treatment strategies have emerged for the management of patients with metastatic hormone sensitive prostate cancer (mHSPC). The addition of docetaxel and/or androgen receptor-axis targeted (ARAT) agents to standard androgen deprivation therapy (ADT), in the form of doublet and triplet treatment strategies, has demonstrated overall survival benefits in this cohort of patients. As such, these drug combinations have changed the standard of care approaches in these men.1
Written by: Rashid K. Sayyid, MD MSc and Zachary Klaassen, MD,MSc
References:
  1. Weiner AB, Siebert AL, Fenton SE, et al. First-line Systemic Treatment of Recurrent Prostate Cancer After Primary or Salvage Local Therapy: A Systematic Review of the Literature. Eur Urol Oncol. 2022.
  2. Cancer Stat Facts: Prostate Cancer. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/prost.html. Accessed: Nov 14, 2022
  3. Deek MP, Van der Eecken K, Phillips R, et al. The mutational landscape of metastatic castration-sensitive prostate cancer: the spectrum theory revisited. Eur Urol. 2021;80:632-640
  4. Stopsack KH, Nandakumar S, Wimber AG, et al. Oncogenic genomic alterations, clinical phenotypes, and outcomes in metastatic castration-sensitive prostate cancer. Clin Cancer Res. 2020;26:3230-3238.
  5. Sweeney CJ, Chen Y, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N ENgl J Med. 2015;373:737-746.
  6. Fizai K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2022;399(10336):1695-1707.
  7. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022;386(12):1132-1142.
  8. Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121-131.
  9. Hoyle AP, Ali A, James ND, et al. Abiraterone in “High-” and “Low-risk” Metastatic Hormone-sensitive Prostate Cancer. Eur Urol. 2018;76(6):719-728.
  10. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377:338-351.
  11. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021;39(2):2294-2303.
  12. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986.
  13. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366.
  14. Boeve LMS, Hulshof MCCM, Vis AN, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019;75(3):410-418.
  15. Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446-453.
  16. Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020;6(5):650-659.
  17. Deek MP, van der Eecken K, Sutera P, et al. Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials. J Clin Oncol. 2022;JCO2200644.
  18. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058.
Page 3 of 10