Genitourinary Toxicity, Function, and Quality of Life in Patients Undergoing Prostate Radiation Therapy—A Scoping Review

ABSTRACT

The effects of prostate radiotherapy (external beam radiation therapy (EBRT) and brachytherapy (BRT)) on urinary adverse events (UAEs), lower urinary tract function, and quality of life were examined in this scoping review. PubMed, Cochrane, and Embase (OVID) were used to identify relevant articles. We discuss the results of 23 studies. Included studies showed that UAEs are common after prostate radiation therapy. Across modalities, approximately one third experience acute events (Grade ≥ 2 median 36% for both EBRT and BRT), while one quarter experience late events (Grade ≥ 2 median 20% for EBRT and 26% for BRT). These estimates vary by UAE grading definitions and study designs. In the long term, patients with mild lower urinary tract symptoms (LUTS) report minimal improvement or worsening of urinary function after radiotherapy. Patients with moderate to severe baseline LUTS experience improvement in general but continue to experience bothersome LUTS. The limited urodynamic data show a similar pattern in which peak flow rate declines and post‐void residual increases in the short term but return to baseline after long‐term follow‐up. These findings underscore the need for additional research to improve patient management and selection, and thereby improve genitourinary toxicity, function, and quality of life with contemporary radiotherapy techniques.

1. Background

Prostate cancer (PCa) is the most frequently diagnosed cancer in men [1]. Concomitant lower urinary tract symptoms (LUTS) are common, with 40% of patients having LUTS at PCa diagnosis [2]. Treatment modalities for localized PCa, such as a radical prostatectomy, external beam radiation therapy (EBRT), and brachytherapy (BRT), have similar long‐term oncological outcomes [3]. Treatment choice and patient counseling should therefore be based upon other factors impacting genitourinary, bowel, and sexual function [4].

Well‐known urinary adverse events (UAE) associated with radiation therapy are hematuria, urgency, and acute urinary retention. Within 10 years, 20% of patients treated with BRT or EBRT for PCa undergo subsequent interventions for UAE. However, these risks are comparable to a 17% intervention rate in non‐cancer controls not receiving radiotherapy [5].

The effects of radiation therapy on lower urinary tract (LUT) function and subsequent quality of life (QoL) are less well studied. Radiation therapy can cause urgency, edema, stricture formation, and/or radiation cystitis, which impair LUT function [6]. However, the concomitant use of androgen deprivation therapy (ADT) and radiation itself causes a reduction of prostate volume, which can improve voiding LUTS [7, 8].

In this scoping review, the impact of radiation therapy for PCa on LUT function, QoL, and UAE is evaluated. This review does not include erectile dysfunction.

2. Methods

PubMed, Cochrane, and Embase (OVID) were used to identify relevant articles. Title and abstracts were screened for relevance by both the authors' C.V. and T.H. Studies were included in case they reported data on urinary adverse events, functional outcomes, and/or quality of life following radiotherapy. Only publications within the last 25 years were selected. Non‐English papers and reports without a full text were excluded. The following terms were combined: ‘Prostate cancer’, ‘Radiotherapy’, ‘Brachytherapy’, ‘External Beam Radiotherapy’, ‘Functional Outcomes’ and ‘International Prostate Symptom Score (IPSS)’. Only publications in English within the last 25 years were selected. References of relevant papers were screened to identify additional relevant papers.

To compare different EBRT and BRT dosages and fractions, equivalent dose in 2 Gy fractions (EQD2) calculations were performed using GEC‐ESTRO handbook of Brachytherapy [9], which are depicted in Table 1. For the calculations, α/β was set at 3, with a tissue half‐time repair of 1.5 h, and effective treatment for I‐125 implants was considered 12 months, calculating the effective dose range.

TABLE 1.

Urinary adverse events in patients undergoing radiation therapy for prostate cancer.

Study (year)	Design	N	Type of radiation therapy	Median prescribed dose in Gy (fractions)	EQD2 dose***	Concomitant ADT	Median age (years)	Follow‐up (months)	CTCAE acute (grade)	CTCAE late (grade)	RTOG acute (grade)	RTOG late (grade)
EBRT + SBRT
Van As et al. (2024)—EBRT	RCT	441	EBRT	62 (20)	73.4	0%	70	74	—	29% (Grade ≥ 2)	—	27% (Grade ≥ 2)
Van As et al. (2024)—SBRT	RCT	433	SBRT	36.25 (5)	78	0%	70	74	—	42% (Grade ≥ 2)	—	18% (Grade ≥ 2)
Tombolini et al. (2009)	Prospective	51	EBRT: IMRT	54 (15)	71.3	100%	75	34	—	—	—	—
Pastorello et al. (2017)	Prospective	60	EBRT: IMRT	76–78 (38–39)	76.0–78.0	—	74	60	—	—	—	—
Choo et al. (2002)	Prospective	17	EBRT	70 (35)	—	—	72	18	—	—	—	—
Zelefsky et al. (2006)	Prospective	367	EBRT: IMRT	81 (45)	77.8	35.0%*	N/A	63	44% (Grade ≥ 2)	23% (Grade ≥ 2)	—	—
Aghdam et al. (2020)	Prospective	53	SBRT	35–36 (5)	70.0–73.4	30.2%	71	60	—	9% (Grade > 3)	—	—
Jarosek et al. (2015)—EBRT	Matched	44.318	EBRT	—	—	—	> 65	50	—	20% (Grade > 3)	—	—
Chevli et al. (2016)	Retrospective	368	EBRT: IMRT	77–81 (43–45)	73.8–77.8	12.5%	68	12	—	3% (Grade ≥ 1)	—	—
Ghadjar et al. (2013)	Retrospective	268	EBRT: IMRT	86 (48)	82.4	50%	71	60	28% (Grade ≥ 2)	20% (Grade ≥ 2)	—	—
Takeda et al. (2021)	Retrospective	452	EBRT: IMRT	76–80 (38–40)	76–80	96%	69	83	—	6% (Grade 3)	—	—
Malik et al. (2011) (pre‐RT IPSS ≥ 15)	Retrospective	80	EBRT: 3D‐CRT (15%) & IMRT (85%)	69–76 (NA)	—	45%	69	40	—	9% (Grade ≥ 2)	64% (Grade ≥ 2)	62% (Grade ≥ 2)
Malik et al. (2011) (pre‐RT IPSS < 15)	Retrospective	288	EBRT: 3D‐CRT (15%) & IMRT (85%)	69–76 (NA)	—	50%	69	40	—	—	42% (Grade ≥ 2)	36% (Grade ≥ 2)
Salami et al. (2016)—Mild group	Retrospective	2092	EBRT: IMRT	81 (45)**	77.8**	46.7%**	71**	24**	—	—	—	—
Salami et al. (2016)—Moderate group	Retrospective	1276	EBRT: IMRT	81 (45)**	77.8**	46.7%**	71**	24**	—	—	—	—
Salami et al. (2016)—Severe group	Retrospective	233	EBRT: IMRT	81 (45)**	77.8**	46.7%**	71**	24**	—	—	—	—
Tomita et al. (2015)—Mild group	Retrospective	124	EBRT: IMRT	78	—	11	68	36	—	—	17% (Grade ≥ 2)	9% (Grade ≥ 2)
Tomita et al. (2015)—Moderate group	Retrospective	70	EBRT: IMRT	77	—	10	70	34	—	—	31% (Grade ≥ 2)	10% (Grade ≥ 2)
Tomita et al. (2015)—Severe group	Retrospective	22	EBRT: IMRT	77	—	11	69	35	—	—	36% (Grade ≥ 2)	9% (Grade ≥ 2)
Arscott et al. (2014)	Retrospective	269	SBRT	35 (5)	70	16%	69	36	40% (Grade ≥ 2)****	41% (Grade ≥ 2)****	—	—
BRT (+ EBRT boost):
Michalski et al. (2023)—LDR group	RCT	282	LDR 125I‐or 103Pd BRT	145	89.1	9%	67	144	22% (Grade ≥ 2)	—	—	45% (Grade ≥ 2)
Michalski et al. (2023)—LDR + EBRT group	RCT	287	LDR 125I‐or 103Pd BRT + EBRT	BRT + EBRT: 110 + 45 (25)	BRT + EBRT: 67.2 (I125) + 43.2	8%	67	144	21% (Grade ≥ 2)	—	—	28% (Grade ≥ 2)
Tanaka et al. (2009)	Prospective	110	LDR 125I‐BRT (74.5%) and LDR 125I‐BRT + EBRT (25.5%)	BRT: 145, BRT + EBRT: 110 + 45 (25)	BRT: 89.1, BRT + EBRT: 67.2 + 43.2	38.1%*	67	12	—	—	—	—
Tanaka et al. (2019)—LDR group	Prospective	1792	LDR 125I‐BRT	144	88.4	41*	68	60	67% (Grade ≥ 1)	24% (Grade ≥ 1)	—	—
Tanaka et al. (2019)—LDR + EBRT group	Prospective	547	LDR 125I‐BRT + EBRT	100–110 + 40–50 (20–28)	61.0–67.2 + 40.0–48.4	72*	69	60	50% (Grade ≥ 1)	22% (Grade ≥ 1)	—	—
Aaltoma et al. (2008)	Prospective	444	LDR 125I‐BRT	140	85.9	18%	65	24	—	—	—	—
Beekman et al. (2005)	Prospective	204	LDR 125I‐BRT + EBRT (60%)	—	—	40%	64	12	—	—	—	—
Chinenov et al. (2024)	Prospective	52	LDR 125I‐BRT	—	—	N/A	67	36	—	—	—	—
Ikeda et al. (2008)	Prospective	273	LDR 125I‐or 103Pd BRT + EBRT (22%)	—	—	21%	64	N/A	—	—	—	—
Jarosek et al. (2015)—BRT	Matched	14.259	BRT	—	—	—	> 65	50	—	20% (Grade ≥ 3)	—	—
Jarosek et al. (2015)—EBRT + BRT	Matched	11.835	BRT + EBRT	—	—	—	> 65	50	—	28% (Grade ≥ 3)	—	—
Martens et al. (2006)	Retrospective	207	LDR 125I‐BRT	—	—	11.8%*	64	—	—	—	—	—
Williams et al. (2004)	Retrospective	173	LDR 125I‐BRT	—	—	16.8%*	61	19	—	—	—	—

Note: *Neoadjuvant ADT instead of concomitant. **Mean/median values for the whole study. *** Calculated using α/β = 3, tissue half time repair 1.5 h, and effective treatment time = 12 months. ****Only urinary retention was scored.

3. Overview of Included Studies

In total, 23 studies were selected, of which 13 (50%) were prospectively conducted (Table 1). A flowchart depicting study selection is shown in Figure 1. Study descriptions, radiation therapy dose, use of androgen deprivation therapy (ADT), along with UAE are presented in Table 1. IPSS and uroflowmetry results are depicted in Table 2. Concurrent ADT was administered in 13% [10, 11] to 100% [12, 13] of participants. Early UAE was commonly defined as occurring within 3 months after the start of therapy. The Common Terminology for the Classification of Adverse Events (CTCAE) was most often used [5, 10, 13, 14, 15, 16, 17], while two studies utilized the Radiation Therapy and Oncology Group (RTOG) definitions [15, 18]. Whereas the CTCAE offers a broad classification system for adverse events, the RTOG scale focuses specifically on radiation‐induced toxicity. An overview of CTCAE and RTOG grades is depicted in Table 3; a lower score indicates milder UAE.

FIGURE 1.

Flowchart describing identification of included papers.

TABLE 2.

International prostate symptom score and uroflowmetry results in patients undergoing radiotherapy for prostate cancer.

Study (year)	N	Type of radiation therapy	Follow‐up in (months)	Total IPSS baseline	Total IPSS last follow‐up	Post voiding residual baseline	Post voiding residual last follow‐up	Peak flow‐rate baseline	Peak flow‐rate last follow‐up
EBRT + SBRT
Tombolini et al. (2009)	51	EBRT: IMRT	34	—	—	61 mL	84 mL	14 ml/s	14 ml/s
Pastorello et al. (2017)	60	EBRT: IMRT	60	7	9	40 mL	81 mL	15 ml/s	12 ml/s
Choo et al. (2002)	17	EBRT	18	7	7	—	—	—	—
Aghdam et al. (2020)	53	SBRT	60	20	14	—	—	—	—
Chevli et al. (2016)	368	EBRT: IMRT	12	7	6	—	—	—	—
Ghadjar et al. (2013)	268	EBRT: IMRT	60	7	7	—	—	—	—
Malik et al. (2011) (pre‐RT IPSS ≥ 15)	80	EBRT: 3D‐CRT (15%) & IMRT (85%)	40	18	13	—	—	—	—
Malik et al. (2011) (pre‐RT IPSS ≥ 15)	288	EBRT: 3D‐CRT (15%) & IMRT (85%)	40	6	5	—	—	—	—
Salami et al. (2016)—Mild group	2092	EBRT: IMRT	24**	4	5	—	—	—	—
Salami et al. (2016)—Moderate group	1276	EBRT: IMRT	24**	12	10	—	—	—	—
Salami et al. (2016)—Severe group	233	EBRT: IMRT	24**	24	13	—	—	—	—
Tomita et al. (2015)—Mild group	124	EBRT: IMRT	36	6	5	—	—	—	—
Tomita et al. (2015)—Moderate group	70	EBRT: IMRT	34	13	10	—	—	—	—
Tomita et al. (2015)—Severe group	22	EBRT: IMRT	35	24	14	—	—	—	—
BRT (+ EBRT boost)
Tanaka et al. (2009)	110	LDR 125I‐BRT (74.5%) and LDR 125I‐BRT + EBRT (25.5%)	12	9	10	17 ml	24 mL	13 ml/s	12 ml/s
Aaltoma et al. (2008)	444	LDR 125I‐BRT	24	8	9	40 ml	—	15 ml/s	14 ml/s
Beekman et al. (2005)	204	LDR 125I‐BRT + EBRT (60%)	12	7	5	13 ml	—	—	—
Chinenov et al. (2024)	52	LDR 125I‐BRT	36	8	8	—	—	14 ml/s	13 ml/s
Ikeda et al. (2008)	273	LDR 125I‐or 103Pd BRT + EBRT (22%)	N/A	7	—	44 mL	—	15 ml/s	—
Martens et al. (2006)	207	LDR 125I‐BRT	NA	9	—	29 mL	—	17 ml/s	—
Williams et al. (2004)	173	LDR 125I‐BRT	19	4	8	—	—	19 mL/s	—

TABLE 3.

Definitions of common terminology for related adverse events (CTCAE) and radiation therapy oncology group (RTOG) grading of urinary adverse events.

Grade of toxicity	CTCAE	RTOG—early	RTOG—late
I	Mild symptoms without need for intervention	Frequency of urination. Nocturia twice pretreatment habit, dysuria and urgency not requiring medication	Slight epithelial atrophy, minor telangiectasia and microscopic hematuria
II	Symptoms requiring intervention and/or medical therapy without hospitalization	Frequency of urination or nocturia that is less frequent than every hour. Dysuria, urgency, bladder spasm requiring local anesthetic	Moderate frequency, generalized telangiectasia, intermittent macroscopic hematuria
III	Hospitalization, intravenous therapy, transfusion or elective invasive intervention	Frequency with urgency and nocturia hourly or more, dysuria, pelvic pain, bladder spasm requiring frequent narcotic, gross hematuria with or without clot passing	Severe frequency and dysuria, severe telangiectasia, frequent hematuria, reduction in bladder capacity (< 150 cc)
IV	Life‐threatening events requiring acute intervention	Hematuria requiring transfusion, acute bladder obstruction not secondary to clot passage, ulceration, or necrosis	Necrosis/contracted bladder, capacity < 100 cc, severe hemorrhagic cystitis
V	Death	—	—

4. Urinary Adverse Events

In a large, matched cohort by Jarosek et al., the most common causes of UAE in both the EBRT and BRT groups were radiation cystitis (10‐year propensity weighted cumulative incidence; EBRT: 5.0%; BRT: 4.8%), urethral stricture and/or bladder neck contracture (EBRT: 9.6%; BRT: 11.9%), and prostate obstruction (EBRT: 5.8%; BRT: 7.4%). Uncommon causes are fistula formation (EBRT: 0.1%; BRT: 0.1%) and incontinence (EBRT: 0.3%; BRT: 0.6%) [5]. A large prospective study by Tanaka et al. reported significantly higher rates of CTCAE acute grade ≥ 1 UAE (< 3 months) in patients receiving low‐dose rate (LDR)‐BRT (67%) compared to LDR‐BRT + EBRT (50%), although this was not significant after 12 months (24% vs. 22%). In multivariable analysis, older age, larger prostate size, higher pretreatment IPSS, and drinking status were independent predictors of acute grade ≥ 2 toxicity [13]. In a recent randomized controlled (PACE‐B) trial comparing EBRT versus stereotactic body radiation therapy (SBRT), 5‐year grade ≥ 2 RTOG rates were 7% and 5%, respectively [19]. In a recent randomized clinical trial comparing LDR‐BRT versus LDR‐BRT + EBRT, acute rates of RTOG UAE did not significantly differ (22% vs. 22%), but late grade 2 UAE were more common in the LDR + EBRT group (37% vs. 25%) [20]. Kim et al. reported a ≥ 2 UAE incidence of 26% in another population‐based cohort (n = 60 134) of patients receiving either EBRT, BRT, or both over a median follow‐up of 94 months [21]. In terms of retrospective studies, Ghadjar et al. described acute and late CTCAE grade ≥ 2 UAE rates of 28% and 21%, respectively, in 268 patients who underwent intensity‐modulated radiation therapy (IMRT) [14]. Takeda et al. reported CTCAE grade III UAE rates of 5% in a retrospective cohort receiving IMRT, where antiplatelet therapy and prior high‐intensity focal ultrasound ablation of the prostate were significant risk factors for UAE.

Malik et al. (n = 368) compared RTOG UAE rates for patients with pre‐EBRT baseline IPSS scores of ≥ 15 versus < 15. The acute/late ≥ grade 2 UAE incidence rates were significantly higher in the ≥ 15 IPSS group (64%/62%) versus the < 15 IPSS group (42%/36%) [15]. Tomita et al. reported late RTOG grade ≥ 2 UAE of 9% in patients similarly receiving IMRT [18]. Arscott (n = 269) and Williams et al. (n = 173) retrospectively reviewed the incidence of grade acute urinary retention (AUR) for patients who underwent SBRT and BRT, respectively. Acute and late urinary retention rates were 40% and 42% for patients receiving SBRT. However, urinary retention was defined as complaints of hesitancy and/or prescription of an alpha blocker [16] and compared to an overall reported urinary retention rate of 20% in the BRT study (follow‐up of 18.8 months) [16, 22].

5. Lower Urinary Tract Function

5.1. IPSS

IPSS was included in 16 studies [10, 11, 13, 14, 15, 17, 18, 22, 23, 24, 25, 26, 27, 28, 29, 30]. Baseline IPSS scores varied from 4 to 20 [17, 22], and follow‐up ranged from 12 to 60 months. No significant differences were reported between IPSS at baseline and last follow‐up [10, 11, 13, 14, 18, 23, 24, 26, 27, 28, 30]. Longitudinal data for patients with mild (IPSS ≤ 7) and moderate to severe LUTS (IPSS > 7) are depicted in Figure 2A,B, respectively.

FIGURE 2.

Serial assessment of IPSS in patients with none to mild (A) and moderate to severe (B) lower urinary tract symptoms undergoing radiotherapy for prostate cancer.

In a prospective cohort of LDR‐BRT (75%) vs. LDR‐BRT + EBRT (25%), mean IPSS scores increased from 9 at baseline to 17 after 3 months and decreased to 10 after 12 months [13]. In an RCT comparing SBRT with EBRT, IPSS did not significantly change in both groups after 24 months. Baseline IPSS was 6 in both groups and increased to 7 in the SBRT group but remained 6 in the EBRT group [24]. In another prospective study including patients undergoing SBRT with a baseline IPSS ≥ 15, median baseline IPSS declined from 20 to 13 after 3 months and was 14 after 36 months. Retrospectively, Ghadjar et al. found that changes in IPSS after IMRT were dependent on baseline LUT function. In patients with mild symptoms (IPSS 0‐7), a median increase of 4 points was seen, versus 2 and 0 in patients with moderate (IPSS 8‐19) and severe baseline symptoms (IPSS 20‐35) [14]. Using a similar stratification method, Tomita et al. reported a mean increase of 2 points (4 to 5) in the mild group, a decrease of 3 points (13 to 10) in the moderate group and a decrease of 9 points in the severe group (24 to 14) 24 months after receiving IMRT [18]. Additionally, Salami et al. reported that patients with severe baseline IPSS had the largest decrease in mean IPSS scores (from 24.0 to 13.4), compared to the moderate (12 to 10) and mild groups (4 to 5), 24 months after IMRT [23]. Williams et al. reported a mean baseline IPSS of 4, which rose to 16 after 3 months and decreased to 8 after 12 months in a retrospective cohort of BRT recipients [22]. In two larger prospective BRT cohorts (n = 204 and n = 273), baseline IPSS did not significantly differ between first (7 and 8, respectively) and last follow‐up (9 and 8, respectively) [27, 29].

5.2. Urodynamic Studies

We identified nine studies in which LUT function using uroflowmetry was measured. Tanaka et al. reported a mean baseline micturition volume (MV) of 236 mL, peak flow rate (PFR) of 13 mL/s, and post‐void residual (PVR) of 17 mL, which significantly worsened to respectively, 183 mL (MV), 12 mL/s (PFR), and 21 mL (PVR) after 6 months in 110 patients receiving BRT or BRT and EBRT. Uroflowmetry parameters returned to baseline after 12 months (MV 206 mL, PFR 12 mL/s, PVR 25 mL) in this prospective cohort [31]. Tombolini et al. observed no differences in PFR at 12 (13 mL/s) and 28 (14 mL/s) months after IMRT compared to baseline (14 mL/s) in their prospective cohort [11]. In two prospective BRT cohorts, baseline PFR (15 and 14 mL/s, respectively) declined in the first 6 months (11 and 12 mL/s) but steadily increased until last follow‐up (14 and 14 mL/s), after 24 and 36 months, respectively [26, 28]. Martens et al. found that lower baseline PFR was associated with post‐BRT urinary retention requiring catheterization (Odds ratio (OR): 0.85, p = 0.004) in a retrospective study [12]. Similarly, Ikeda et al. reported that lower PFR was multivariately associated as a risk factor for AUR after BRT (AUR group PFR = 9.84 (±3.6) vs. non‐AUR group 15.1 mL (±7), p = 0.030) [29].

Do et al. described the results of 17 patients undergoing multichannel video‐urodynamic studies at 3 and 18 months after EBRT. After 3 months, there was a decrease in bladder capacity of 70 mL (p = 0.028), and patients had a significantly earlier first bladder sensation (145 mL versus 230 mL, p = 0.033) [30, 32]. The reduced bladder capacity persisted after 18 months, with a mean reduction of bladder volume of 100 mL (p = 0.0002). There was no significant change in bladder compliance or bladder outlet obstruction after 18 months. Both at 3 and 18 months, there were no significant differences in self‐reported outcomes such as the IPSS or frequency assessed by voiding diaries [30, 32].

Pastorello et al. performed multiple urodynamic evaluations in 60 patients undergoing EBRT. They observed a decrease in cystometric capacity (380 mL baseline versus 288 mL) and a decrease in PFR (10 mL/s versus 8 mL/s) with a subsequent increase in bladder outlet obstruction index (16 versus 18), 2 months after EBRT. After 18 months, cystometric capacity improved again to 350 mL and remained stable up to 60 months (350 mL) [25].

6. Quality of Life

In a prospective cohort, IPSS‐QoL was 2 at baseline, rose to 3 at 3 months, and remained 3 at 1 year after radiotherapy. Aghdam et al. reported in their prospective cohort of patients with high baseline IPSS‐scores (mean 20) undergoing SBRT that obstructive and irritative complaints significantly improved over 3 years. The Extended Prostate Cancer Index Composite‐26 (EPIC‐26) scores for obstructive and irritative complaints rose from 64 to 77 (indicating improvement). The PACE‐B RCT indicated that IPSS‐QOL at baseline vs. 2 years was 2 vs. 1 for patients undergoing EBRT and 1 vs. 1 for patients undergoing SBRT, respectively [24]. Urinary incontinence‐related QOL did not significantly change (80 at baseline vs. 78 at 36 months) [17]. In several retrospective studies, including patients undergoing EBRT [14, 15] and BRT [13], IPSS‐QoL did not significantly differ between baseline and last follow‐up.

7. Discussion

This narrative review assessed the effects of radiation therapy on UAE, LUT function, and QoL in patients with PCa.

Included studies showed that UAEs are common after prostate radiation therapy. Across modalities, approximately one third experience acute events (Grade ≥ 2 median 36% for both EBRT and BRT), while one quarter experience late events (Grade ≥ 2 median 20% for EBRT and 26% for BRT). These estimates vary by UAE grading definitions and study designs. In a recent meta‐analysis, it was suggested that both acute UAE (n = 2 studies, risk ratio 2.32, confidence interval (CI): 1.29–4.15, p = 0.005) and late UAE (n = 3 studies, risk ratio 2.38; CI 1.27–4.44, p = 0.007) are more common in patients undergoing LDR‐BRT compared to EBRT alone [33]. However, these differences were not observed in our review. While the 10‐year incidence of radiation cystitis is roughly 5% in both EBRT and BRT, it is worthwhile to mention that these complications are often difficult to treat and resolve [34].

It is important to acknowledge that a large proportion of the included studies were conducted retrospectively. Furthermore, substantial heterogeneity was present in treatment regimens, including radiotherapy dose, fractionation schedules, and the use of neoadjuvant or adjuvant ADT. Additionally, for the reported outcome measures, different grading scales were used. These limitations restrict the ability to draw strong comparative conclusions.

Most studies serially assessing IPSS report a trend in which urinary function worsens in the first 3–6 months after radiation therapy but steadily improves afterwards [10, 13, 18, 22]. The improvement of IPSS can, at least in part, be attributed to the concomitant or neoadjuvant use of ADT, which generally causes a reduction in prostate volume and thereby improves LUTS over several months [35]. However, it should be noted that prostate volume reduction might be transient, with prostate volume increasing after testosterone recovery when ADT is completed or discontinued. Given that in patients undergoing radiation therapy alone, prostate volume also decreases due to the antiproliferative effect of radiotherapy on natural benign hypertrophic evolution [8], this forms an alternative explanation. Additional research on the effects of ADT is needed to better understand the combined and long‐term effects of prostate cancer treatment on urinary function.

Importantly, patients with moderate (8–19) to high IPSS scores (20–35) receiving EBRT show significantly more improvement than patients with mild symptoms (IPSS 0‐7), which also seems to translate into IPSS‐QOL [13, 15, 17]. It is of importance to note that patients with high baseline IPSS improve but still end up with IPSS scores equaling moderate to bothersome symptoms [15, 17, 18, 23]. Furthermore, IPSS is not a very specific tool to assess LUT function. This trend was not observed in studies with BRT, probably given the stricter exclusion of patients with bothersome LUTS or poor uroflowmetry [12]. Only a minority of studies reported the outcomes of urodynamic studies. For patients receiving BRT, a similar trend to the subjective assessment was described; urinary function worsened in the short term, with subsequent return to baseline after 1 year [26, 28, 29, 31]. In one study assessing uroflowmetry in patients receiving EBRT, PFR did not seem to change over time, while PVR significantly increased after 6 and 12 months [11], although the absolute difference is of no significant clinical impact. In the three studies reporting multichannel urodynamic findings, bladder capacity notably decreased during follow‐up, presumably due to radiotherapy induced fibrosis [25, 30, 32]. However, no significant changes in bladder outlet obstruction or bladder compliance were observed in the study by Do et al. [30, 32].

Although some studies have suggested that a history of prior deobstructive surgery is associated with an increased risk of UAE in patients undergoing prostate radiotherapy [36], some smaller studies have shown that neoadjuvant deobstruction might reduce LUTS at baseline and therefore reduce urinary toxicity in patients undergoing BRT [37, 38, 39].

The aim of this review was not to compare older and newer radiotherapy techniques, such as EBRT versus SBRT. However, no apparent differences were observed. Although cancer‐free survival seems to be similar between EBRT and SBRT [40], its effect on urinary adverse events and function is less known. Interestingly, the 5‐year outcomes of the HYPO‐RT‐PC trial suggested higher rates of acute urinary toxicity for SBRT compared to EBRT [41], while the recent PACE‐B trial found no difference between UAE rates for EBRT and SBRT. SBRT is patient‐friendly, given the less frequent visits to the hospital. Additionally, the increasing use of rectal spacer technologies reduces the rectal dose exposure, thereby limiting gastrointestinal and genitourinary side effects [42].

From a clinical perspective, this review emphasizes the importance of baseline urinary function assessment, as patients with moderate to severe LUTS can expect improvement when receiving EBRT in combination with ADT, while those with mild symptoms see little benefit or worsening of their urinary function, regardless of the radiotherapy modality. Although the improvement of LUTS can at least partially be explained by the use of ADT, its use should be weighed against the systemic side effects of ADT. It is currently unclear whether patients with moderate to severe LUTS might benefit from neoadjuvant deobstruction. Alternatively, when feasible, patients with significant LUTS can be counseled for robot‐assisted radical prostatectomy. Regardless of the radiotherapy modality, urinary adverse effects are common. About 1 in 4 patients experience short‐term UAE, while 1 in 3 experience long‐term UAE. Although radiation cystitis is relatively rare (5% for both EBRT and BRT) [5], it is difficult to treat. Data on the urodynamic impact of radiotherapy are scarce, underscoring the need for additional prospective studies assessing both subjective (such as the IPSS) and objective measures (uroflowmetry and ideally multichannel urodynamic studies) at baseline and during follow‐up. This might especially be of interest for newer techniques, such as magnetic resonance guided radiotherapy.

8. Conclusion

This review highlights the significant impact of radiotherapy on UAE, LUT function, and QoL in patients with PCa. For both EBRT and BRT, acute and late urinary toxicity is common. In the long term, patients with mild lower urinary tract symptoms see minimal improvement or worsening of their urinary function, while patients with moderate to severe baseline symptoms generally experience significant improvement as defined by the IPSS. The limited urodynamic data show a similar pattern in which peak flow rate declines and post‐void residual increases in the short term but return to baseline after long‐term follow‐up. These findings underscore the need for additional research to improve patient management and selection, and thereby improve genitourinary toxicity, function, and quality of life with contemporary radiotherapy techniques.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Vrij C., Heesakkers J., Van Limbergen E. J., et al., “Genitourinary Toxicity, Function, and Quality of Life in Patients Undergoing Prostate Radiation Therapy—A Scoping Review,” LUTS: Lower Urinary Tract Symptoms 18, no. 1 (2026): e70046, 10.1111/luts.70046.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.