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| Genitourinary toxicity after pelvic radiation: Prospective review of complex urological presentations |
Rowan V. Davida,b,*( ),Asif Islama,John Millera,Michael E. O'Callaghana,b,Arman A. Kahokehra,b
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aDepartment of Urology, Lyell McEwin Hospital, Elizabeth Vale, Adelaide, Australia
bCollege of Medicine and Public Health, Flinders University, Bedford Park South Australia, Adelaide, Australia |
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Abstract Objective: Recent randomised controlled trials underestimated the incidence of genitourinary (GU) complications occurring more than 5 years following pelvic radiotherapy. This study aimed to determine the burden of treatment at a single institution from late GU complications after pelvic radiotherapy. Methods: A prospective study of all presentations for GU complications following pelvic radiotherapy at a tertiary urology department between November 2018 and November 2019 was performed. Subgroup analyses was performed on patients with prostate cancer (PCa) with late toxicity to compare patient demographics, radiotherapy, complications, and management factors. Results: There were 117 hospital encounters involving 46 patients with a 56.4% repeat encounter rate. Patients with PCa were the predominant group (n=39, 84.8%). External beam radiotherapy was the most common treatment modality (n=41, 89.1%). The median time from radiotherapy to encounter was 8 (range 0-23) years. Radiation-induced haemorrhagic cystitis was the most common presentation (n=70, 59.8%). Forty-four (42.7%) encounters for GU toxicity were managed operatively and 33 (32.0%) involved a non-operative procedure. Nine patients required packed red cell transfusion, with a total of 154 units transfused. Patients with PCa who presented with late GU toxicity had higher median Radiotherapy Oncology Group grades (p=0.020), proportion of emergency admissions (p=0.047), and frequency of clot urinary retention (p<0.001). Conclusion: There is a high burden of elective and emergency urology workload attributed to late pelvic radiation toxicity. Late GU toxicity occurring ≥5 years after radiotherapy is common and often more severe.
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Received: 21 July 2022
Available online: 20 October 2024
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Corresponding Authors:
* College of Medicine and Public Health, Flinders University, Bedford Park South Australia, Adelaide, Australia E-mail address: rowanvictordavid@gmail.com (R.V. David).
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| Characteristic | Overall, n=46 | Time from radiotherapy | | <5 years, n=15 | ≥5 years, n=31 | p-Valuea | | Toxicityb | | | | 0.72c | | Fistula | 1 (2.2) | 0 (0) | 1 (3.2) | | | Haematuria | 34 (73.9) | 11 (73.3) | 23 (74.2) | | | Incontinence | 1 (2.2) | 1 (6.7) | 0 (0) | | | RASM | 2 (4.3) | 1 (6.7) | 1 (3.2) | | | Retention | 2 (4.3) | 0 (0) | 2 (6.5) | | | Stricture | 6 (13.0) | 2 (13.3) | 4 (12.9) | | | Age, year | | | | <0.01d | | Median (IQR) | 71 (65-76) | 76 (72-80) | 68 (64-72) | | | Range | 49-85 | 55-85 | 49-82 | | | CCIb | | | | 0.61e | | ≤7 | 27 (58.7) | 8 (53.3) | 19 (61.3) | | | >7 | 19 (41.3) | 7 (46.7) | 12 (38.7) | | | Antiplateletb | | | | 0.33c | | Yes | 20 (43.5) | 5 (33.3) | 15 (48.4) | | | No | 26 (56.5) | 10 (66.7) | 16 (51.6) | | | Anticoagulantb | | | | >0.99e | | Yes | 12 (26.1) | 4 (26.7) | 8 (25.8) | | | No | 34 (73.9) | 11 (73.3) | 23 (74.2) | | | Primary cancerb | | | | 0.01e | | Bladder | 4 (8.7) | 4 (26.7) | 0 (0) | | | Colorectal | 2 (4.3) | 0 (0) | 2 (6.5) | | | Prostate | 39 (84.8) | 11 (73.3) | 28 (90.3) | | | Vulval | 1 (2.2) | 0 (0) | 1 (3.2) | | | Stage | | | | 0.08c | | ≤2b | 26 (76.5) | 6 (54.5) | 20 (87.0) | | | >2b | 8 (23.5) | 5 (45.5) | 3 (13.0) | | | Missing, n | 12 | 4 | 8 | | | Treatment modalityb | | | | >0.99c | | BT | 2 (4.3) | 0 (0) | 2 (6.5) | | | EBRT | 41 (89.1) | 14 (93.3) | 27 (87.1) | | | EBRT and BT | 3 (6.5) | 1 (6.7) | 2 (6.5) | | | Treatment technique | | | | 0.03c | | IMRTb | 12 (63.2) | 9 (90.0) | 3 (33.3) | | | LDRb | 1 (5.3) | 0 (0) | 1 (11.1) | | | VMATb | 6 (31.6) | 1 (10.0) | 5 (55.6) | | | Missing, n | 27 | 5 | 22 | | | Treatment intent | | | | 0.71c | | Adjuvantb | 2 (4.9) | 0 (0) | 2 (7.4) | | | Curativeb | 32 (78.0) | 12 (85.7) | 20 (74.1) | | | Palliativeb | 2 (4.9) | 0 (0) | 2 (7.4) | | | Salvageb | 5 (12.2) | 2 (14.3) | 3 (11.1) | | | Missing, n | 5 | 1 | 4 | | | Dose, Gy | | | | 0.57e | | ≤70b | 24 (85.7) | 7 (77.8) | 17 (89.5) | | | >70b | 4 (14.3) | 2 (22.2) | 2 (10.5) | | | Missing, n | 18 | 6 | 12 | | | Fraction | | | | 0.84d | | Median (IQR) | 33 (28-35) | 32 (32-33) | 33 (26-35) | | | Range | 20-40 | 23-40 | 20-37 | | | Dose, Gy per fractionb | | | | >0.99c | | <2 | 9 (32.1) | 3 (33.3) | 6 (31.6) | | | ≥2 | 19 (67.9) | 6 (66.7) | 13 (68.4) | |
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Patient demographic and treatment characteristics.
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| Characteristic | Overall, n=39 | Haematuria | | Yes, n=30 | No, n=9 | p-Valuea | | Antiplatelet, n (%) | | | | >0.99 | | Yes | 18 (46.2) | 14 (46.7) | 4 (44.4) | | | No | 21 (53.8) | 16 (53.3) | 5 (55.6) | | | Antiplatelet name, n (%) | | | | >0.99 | | Aspirin | 13 (33.3) | 10 (33.3) | 3 (33.3) | | | Aspirin and clopidogrel | 1 (2.6) | 1 (3.3) | 0 (0) | | | Clopidogrel | 4 (10.3) | 3 (10.0) | 1 (11.1) | | | None | 21 (53.8) | 16 (53.3) | 5 (55.6) | | | Anticoagulant, n (%) | | | | 0.40 | | Yes | 11 (28.2) | 10 (33.3) | 1 (11.1) | | | No | 28 (71.8) | 20 (66.7) | 8 (88.9) | | | Anticoagulant name, n (%) | | | | 0.44 | | Apixaban | 7 (17.9) | 7 (23.3) | 0 (0) | | | Rivaroxaban | 1 (2.6) | 1 (3.3) | 0 (0) | | | Warfarin | 3 (7.7) | 2 (6.7) | 1 (11.1) | | | None | 28 (71.8) | 20 (66.7) | 8 (88.9) | | | Indication, n (%) | | | | 0.24 | | AF | 8 (27.6) | 6 (25.0) | 2 (40.0) | | | CVA | 2 (6.9) | 2 (8.3) | 0 (0) | | | IHD | 9 (31.0) | 9 (37.5) | 0 (0) | | | PE | 2 (6.9) | 2 (8.3) | 0 (0) | | | Primary prevention | 7 (24.1) | 4 (16.7) | 3 (60.0) | | | VTE | 1 (3.4) | 1 (4.2) | 0 (0) | |
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Antiplatelet and Anticoagulant medication details in patients with prostate cancer presenting with radiation-induced haemorrhagic cystitis.
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RTOG grades of genitourinary toxicity events related to urological encounters. RTOG, Radiotherapy Oncology Group.
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Specific genitourinary toxicity events related to urological encounters. RASM, radiation-associated secondary malignancy; BNC, bladder neck contracture.
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| Characteristic | Time from radiotherapy | | <5 years, n=5 | ≥5 years, n=3 | | Post RT UC, n (%) | | CIS | 1 (20.0) | 0 (0) | | HG pTa | 1 (20.0) | 0 (0) | | LG pTa | 2 (40.0) | 2 (66.7) | | HG pT2 | 1 (20.0) | 1 (33.3) | | Age, year | | Median (IQR) | 74 (69-84) | 69 (68-77) | | Range | 67-85 | 67-84 | | CCI, n (%) | | ≤7 | 4 (80.0) | 2 (66.7) | | >7 | 1 (20.0) | 1 (33.3) | | Primary cancer, n (%) | | Bladder | 0 (0) | 0 (0) | | Colorectal | 0 (0) | 0 (0) | | Prostate | 4 (80.0) | 2 (66.7) | | Vulval | 1 (20.0) | 1 (33.3) | | Treatment modality, n (%) | | BT | 2 (40.0) | 2 (66.7) | | EBRT | 2 (40.0) | 1 (33.3) | | EBRT and BT | 1 (20.0) | 0 (0) | | Treatment intent, n (%) | | Adjuvant | 1 (20.0) | 1 (33.3) | | Curative | 4 (80.0) | 2 (66.7) |
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Patients with urothelial carcinoma of the bladder diagnosis following pelvic radiotherapy.
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| Characteristic | Overall, n=103 | Delayed late toxicity | | <5 years, n=33 | ≥5 years, n=70 | p-Valuea | | RTOG grade | | | | 0.020b | | Median (IQR) | 3 (3-4) | 3 (3-3.25) | 4 (3-4) | | | Range | 1-4 | 2-4 | 1-4 | | | Encounter, n (%) | 103 (100) | 33 (100) | 70 (100) | | | Admission, n (%) | 42 (40.8) | 11 (33.3) | 31 (44.3) | 0.29c | | Representation, n (%) | 60 (58.3) | 23 (69.7) | 37 (52.9) | 0.11c | | Unplanned representation, n (%) | 26 (25.2) | 7 (21.2) | 19 (27.1) | 0.52c | | Readmission, n (%) | | | | 0.55d | | Single admission | 84 (81.6) | 28 (84.8) | 56 (80.0) | | | Readmission | 19 (18.4) | 5 (15.2) | 14 (20.0) | | | Unplanned readmission, n (%) | 13 (12.6) | 3 (9.1) | 10 (14.3) | 0.54c | | Encounter category, n (%) | | | | 0.047d | | Elective | 54 (52.4) | 22 (66.7) | 32 (45.7) | | | Emergency | 49 (47.6) | 11 (33.3) | 38 (54.3) | | | Location, n (%) | | | | 0.070d | | ED | 48 (46.6) | 10 (30.3) | 38 (54.3) | | | Flexible cystoscopy clinic | 22 (21.4) | 7 (21.2) | 15 (21.4) | | | OPD | 23 (22.3) | 11 (33.3) | 12 (17.1) | | | OR | 10 (9.7) | 5 (15.2) | 5 (7.1) | | | Length of stay, day | | | | 0.27b | | Median (IQR) | 3 (2-4) | 2 (1-4.5) | 3 (2-4) | | | Range | 1-20 | 1-20 | 1-12 | | | Toxicity type, n (%) | | | | <0.001d | | Necrotic bladder neck contracture | 2 (1.9) | 0 (0) | 2 (2.9) | | | Clot retention | 31 (30.1) | 2 (6.1) | 29 (41.4) | | | High pressure retention | 1 (1.0) | 1 (3.0) | 0 (0) | | | Overactive bladder | 6 (5.8) | 6 (18.2) | 0 (0) | | | Painless haematuria | 34 (33.0) | 15 (45.5) | 19 (27.1) | | | RASM | 4 (3.9) | 1 (3.0) | 3 (4.3) | | | Rectoprostatic fistula | 9 (8.7) | 3 (9.1) | 6 (8.6) | | | Rectovesical fistula | 2 (1.9) | 0 (0) | 2 (2.9) | | | Ureteric stricture | 3 (2.9) | 2 (6.1) | 1 (1.4) | | | Urethral stricture | 11 (10.7) | 3 (9.1) | 8 (11.4) | | | Procedure category, n (%) | | | | 0.51d | | No procedure | 26 (25.2) | 11 (33.3) | 15 (21.4) | | | Non-operative | 33 (32.0) | 8 (24.2) | 25 (35.7) | | | Operative major | 4 (3.9) | 1 (3.0) | 3 (4.3) | | | Operative minor | 40 (38.8) | 13 (39.4) | 27 (38.6) | | | Procedure type, n (%) | | | | 0.09d | | BNI | 1 (1.3) | 0 (0) | 1 (1.8) | | | Continuous bladder irrigation | 27 (35.1) | 5 (22.7) | 22 (40.0) | | | Cystoscopy biopsy | 5 (6.5) | 3 (13.6) | 2 (3.6) | | | Cystoscopy washout diathermy | 3 (3.9) | 0 (0) | 3 (5.5) | | | Defunctioning colostomy | 1 (1.3) | 0 (0) | 1 (1.8) | | | Flexible cystoscopy | 20 (26.0) | 7 (31.8) | 13 (23.6) | | | IDC procedure | 7 (9.1) | 1 (4.5) | 6 (10.9) | | | Nephrostomy exchange | 1 (1.3) | 0 (0) | 1 (1.8) | | | Stent procedure | 2 (2.6) | 2 (9.1) | 0 (0) | | | TOV | 2 (2.6) | 2 (9.1) | 0 (0) | | | TURBT | 3 (3.9) | 1 (4.5) | 2 (3.6) | | | Urethral dilation | 5 (6.5) | 1 (4.5) | 4 (7.3) | |
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Volume of hospital encounters, admissions, and procedures for radiation treatment-related GU toxicity amongst patients with prostate cancer.
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