Correlations of biochemical and clinical outcomes with 10-year results after robotic stereotactic body radiotherapy for localized prostate cancer

Abstract

Background

Long-term data on the efficacy of robotic stereotactic body radiotherapy (SBRT) for localized prostate cancer (LPC) remain limited. This study aimed to evaluate the 10-year treatment outcomes of SBRT in LPC patients and identify key prognostic factors.

Methods

A total of 82 patients with LPC who underwent five-fraction SBRT (doses of 35–37.5 Gy) were included. The median follow-up duration was 11.0 years (range, 3.3–15.9 years). Clinical outcomes, including the biochemical failure-free survival (BCFFS), clinical failure-free survival (CFFS), and prostate-specific antigen (PSA) kinetics, were analyzed to evaluate the impact of various clinical and treatment factors on prognosis.

Results

The 10-year BCFFS and CFFS rates were 86.3% (95% confidence interval [CI], 78.6–94.8) and 86.7% (95% CI, 78.8–95.4), respectively. Nine cases of biochemical failure were observed, alongside local (n = 1), regional (n = 2), and distant (n = 5) metastases. The cancer-specific survival rate was 100%. The median PSA nadir was 0.09 ng/ml (range, 0.0–3.12 ng/ml) and the median interval to PSA nadir was 52.8 months (range, 0.4–170.2 months). There was a negative correlation between the time to the PSA nadir and the PSA nadir value (r = −0.233, p = 0.035). Daily SBRT was associated with improved BCFFS compared to every-other-day treatment (hazard ratio [HR], 0.220; 95% CI, 0.067–0.720; p = 0.012), while a longer interval to PSA nadir (≥ 5 years) was associated with better CFFS (HR, 0.120; 95% CI, 0.015–0.944; p = 0.044).

Conclusions

Robotic SBRT for LPC demonstrates durable long-term efficacy. Daily treatment schedules and interval to PSA nadir were identified as crucial prognostic indicators. These findings highlight the importance of PSA kinetics in predicting treatment success following robotic SBRT.

Background

Prostate cancer is the second most common malignancy, after lung cancer, among men aged ≥ 65 years in Korea, with an age-specific incidence rate of 375.4 per 100,000 in 2020 [1]. Despite an increasing trend in incidence, prostate cancer carries one of the highest cancer survival rates, with a 5-year survival rate of 95.2% [1]. Notably, localized prostate cancer (LPC) accounts for 53.0% of all prostate cancer cases [1]. Treatment options for managing LPC, such as active surveillance, surgery, and radiotherapy (RT), are tailored to the stage, prostate-specific antigen (PSA) level, life expectancy, and a patient’s specific needs [2]. Among them, stereotactic body radiotherapy (SBRT) is widely regarded for its precision, reduced treatment time, and ability to potentially lower toxicity [3]. In prostate cancer, the theoretical biological rationale for SBRT is based on the tumor’s characteristically low α/β ratio compared to that of surrounding normal tissues [4].

A recent phase III study compared five-fraction SBRT (36.25 Gy) to conventional RT regimens (78 Gy in 39 fractions or 62 Gy in 20 fractions) in patients with low-to-intermediate-risk LPC [5]. The 5-year rate of freedom from biochemical failure or clinical failure was 95.8% in the SBRT group compared to 94.6% in the control RT group [5]. However, for late grade 2 or higher toxicity, genitourinary (GU) toxicity was significantly more common in the SBRT group (26.9% vs. 18.4%, p < 0.001), although gastrointestinal (GI) toxicity rates were comparable between the groups (10.7% vs. 10.2%, p = 0.94) [5]. Further, in a meta-analysis of prospective studies of SBRT for LPC, the biochemical failure (BCF)-free survival (BCFFS) rates at 5 and 7 years were 95.3% and 93.7%, respectively [3]. The incidence of late grade 3 GU and GI toxicities was estimated at 2.0% and 1.1%, respectively [3].

While previous studies have demonstrated favorable short- and medium-term outcomes for SBRT in LPC, data on 10-year survival rates and other long-term metrics are limited. The median follow-up duration for the abovementioned phase III trial was 74.0 months and that for the meta-analysis was 39 months [3, 5]. Furthermore, the prognostic significance of PSA kinetics in this context warrants further investigation. Therefore, the present study was conducted to provide an update on the treatment outcomes and toxicity profiles of patients from the Korean Radiation Oncology Group 15−01 study, which analyzed SBRT outcomes for LPC [6]. This study aimed to evaluate the long-term efficacy of robotic SBRT for LPC over a median follow-up of 10 years. By analyzing key prognostic factors, including the PSA nadir and time to nadir, the research sought to provide insights to optimize LPC management and improve patient outcomes.

Methods

Study population

This was a multicenter, retrospective cohort study conducted across three institutions. The medical records of patients diagnosed with LPC who completed SBRT between January 1, 2008, and October 31, 2014, were retrospectively reviewed. The inclusion criteria were: (1) adult males aged ≥ 20 years, (2) histologically confirmed diagnosis of prostate cancer, (3) LPC without pelvic lymph node or distant metastasis, (4) definitive SBRT for LPC, (5) completion of the planned SBRT, and (6) a follow-up period of > 3 years. Patients with a history of other malignant tumors were not excluded. However, patients with a history of previous pelvic RT and those who received SBRT as a boost following whole-pelvis RT were excluded.

Treatment and data collection

SBRT was delivered using the CyberKnife system with gold fiducial markers for prostate motion tracking. Doses of 35–37.5 Gy, delivered in five fractions, were prescribed over consecutive days or every other day (EOD). Treatment planning was performed using computed tomography and magnetic resonance imaging, with the clinical target volume including the prostate and seminal vesicles, and a 3–5 mm margin to create the planning target volume. The dose was normalized to the 75–85% isodose line, with < 1 mL of the rectum receiving 36 Gy and ≤ 5 mL of the bladder receiving 37.5 Gy.

In addition to the patient’s medical records, blood test results, imaging records, and pathology reports, the patient’s risk group was classified based on the initial risk stratification from the National Comprehensive Cancer Network guidelines [7]. The probability of regional lymph node involvement in prostate cancer was calculated using the web-based nomogram from the Memorial Sloan Kettering Cancer Center (https://www.evidencio.com/models/show/440) [8]. BCF was defined according to the Phoenix definition as an increase of >2 ng/mL above the PSA nadir [9]. Clinical failure encompassed cases in which local, regional, or distant metastasis was identified through imaging or tissue biopsy. Acute and late toxicities were assessed using the Radiation Therapy Oncology Group criteria [10].

Statistical analysis

All time-to-event endpoints, including the BCFFS, clinical failure-free survival (CFFS), local control, regional control, distant control, and overall survival (OS), were analyzed using Kaplan-Meier curves. We analyzed the CFFS to examine the correlation between PSA kinetics and clinical outcomes, excluding BCF events. Kaplan–Meier curves for each group were compared using the log-rank test. Pearson’s correlation was used to examine the relationship between the time to the PSA nadir and the PSA nadir value. Univariate analysis of prognostic factors for BCFFS and CFFS were performed using the Cox proportional hazards model. As only a single variable showed statistical significance in the univariate analysis, a multivariate analysis was not conducted. Statistical analyses were carried out using R software (version 4.1.2, https://www.r-project.org/). A two-sided p-value of < 0.05 was considered statistically significant.

Results

A total of 82 patients with LPC were enrolled in this study. Their baseline and treatment characteristics are shown in Table 1. The median follow-up duration was 11.0 years (range, 3.3–15.9 years). The median patient age was 69.5 years (range, 47–81 years). The median initial PSA level was 6.96 ng/ml (range, 2.05–23.04 ng/ml) and the T stage varied: 25 (30.5%) patients were T1c, 17 (20.7%) were T2a, 13 (15.9%) were T2b, 26 (31.7%) were T2c, and 1 (1.2%) was T3a. The Gleason score was ≤ 6 in 53 (64.6%), 7 in 17 (20.7%), and ≥ 8 in 12 (14.6%) patients. Overall, 21 (25.6%) patients were categorized as ≤ low-risk, 47 (57.3%) as intermediate-risk, and 14 (17.1%) as ≥ high-risk. The median lymph node involvement risk was 2% (range, 1–47%).

Table 1.

Baseline characteristics

	n = 82
Follow-up duration (years)	11.0 (3.3–15.9)
Age (years)	69.5 (47–81)
Initial PSA (ng/ml)	6.96 (2.05–23.04)
PSA before SBRT (ng/ml)	6.65 (0.01–21.62)
T stage
1c	25 (30.5)
2a	17 (20.7)
2b	13 (15.9)
2c	26 (31.7)
3a	1 (1.2)
Gleason score
≤ 6	53 (64.6)
7(3 + 4)	12 (14.6)
7(4 + 3)	5 (6.1)
≥ 8	12 (14.6)
Risk group
≤ Low	21 (25.6)
Intermediate	47 (57.3)
≥ High	14 (17.1)
Risk of lymph node involvement (%)a, b	2 (1–47)
ADT before SBRT	11 (13.4)
Duration (months)	2.3 (0.03–3.7)
ADT after SBRT	11 (13.4)
Duration (months)	3.0 (0.03–20.4)
PTV volume (ml)b	92.0 (15.0-220.0)
PTV coverage (%)b	94.7 (82.9–98.5)
Total dose
35 Gy/5 fractions	2 (2.4)
36.25 Gy/5 fractions	20 (24.4)
36.5 Gy/5 fractions	1 (1.2)
37.5 Gy/5 fractions	59 (72.0)
Treatment schedule
Daily	51 (62.2)
Every-other-day	31 (37.8)

Values are indicated as either n (%) or median (range)

^aAccording to the Memorial Sloan Kettering Cancer Center nomogram (available at https://www.evidencio.com/models/show/440)

^bAvailable data only

Abbreviations: ADT, androgen deprivation therapy; PSA, prostate-specific antigen; PTV, planning target volume; SBRT, stereotactic body radiotherapy

Androgen deprivation therapy (ADT) was administered to 11 (13.4%) patients before SBRT and 11 (13.4%) after SBRT. The median duration of ADT was 2.3 months (range, 0.03–3.7) before SBRT and 3.0 months (range, 0.03–20.4) after SBRT. The majority of patients (n = 59, 72.0%) received a total dose of 37.5 Gy in five fractions. The treatment schedule was daily for 51 (62.2%) patients and EOD for 31 (37.8%) patients.

BCF occurred in nine (11.0%) patients, with local, regional, and distant metastases observed in one (1.2%), two (2.4%), and five (6.1%) cases, respectively (Table 2). Table 2 provides the data of patients who experienced treatment failure, and all patients were alive at the time of the last follow-up. Five patients who experienced BCF were observed without further treatment; Over the course of follow-up, three remained disease-free, whereas regional and distant failures occurred in one patient each. Among the 12 patients who experienced treatment failure, three experienced clinical failures without preceding BCF. Additionally, of the five patients who developed distant failure, only one had received ADT before or after SBRT.

Table 2.

Clinical and treatment characteristics of patients experiencing treatment failure after stereotactic body radiotherapy for prostate cancer

Patient	Age	Initial PSA (ng/ml)	T stage	GS	LN riska (%)	ADT	Total dose (Gy)	Treatment schedule	PSA nadir (ng/ml)	PSADT (months)	BCFb	LFb	RFb	DFb	F/U duration
3	67	11.36	1c	6(3 + 3)	-	No	37.5	EOD	0.26	8.2	4y 6 m (→ Mon.)	-	-	-	13y
6	70	3.01	1c	7(3 + 4)	2	No	37.5	EOD	0.01	2.4	3y 11 m (→ Mon.)	-	-	5y (→ ADT)	13y 1 m
13	66	10.32	1c	6(3 + 3)	4	No	37.5	EOD	0.21	29.2	11y 10 m (→ Mon.)	-	-	-	12y 6 m
15	72	16.46	2c	9(5 + 4)	47	No	37.5	EOD	0.63	6.3	2y 11 m (→ W/U)	-	-	3y 1 m (→ Mon.)	4y
26	74	7.19	1c	6(3 + 3)	NA	No	37.5	EOD	0.35	22.5	3y 6 m (→ Mon.)	-	5y (→ ADT)	-	11y 7 m
28	55	6.10	2a	2(1 + 1)	1	No	37.5	EOD	3.12	5.5	10 m (→ S)	-	-	-	11y 3 m
34	66	5.41	2b	6(3 + 3)	2	No	37.5	EOD	0.16	42.5	9y 10 m (→ Mon.)	-	-	-	10y 7 m
38	63	6.02	2b	7(4 + 3)	36	No	36.25	Daily	0.51	-	-	-	4y 3 m (→ S)	-	9y 11 m
60	66	11.07	2c	8(5 + 3)	14	Yesc	37.5	Daily	0.00	-	-	-	-	9y 8 m (→ ADT)	15y 10 m
61	61	9.30	2b	8(4 + 4)	35	Yesd	37.5	Daily	0.00	8.2	3y 6 m (→ ADT)	-	-	-	15y 10 m
65	67	5.78	2b	6(3 + 3)	2	No	37.5	Daily	0.33	24.1	11y 3 m (→ W/Ue)	12y 10 m (→ ADT)	-	12y 10 m (→ ADT)	14y 4 m
80	66	4.55	2a	6(3 + 3)	2	No	37.5	Daily	0.07	-	-	-	-	9y 11 m (→ ADT)	11y 8 m

^aAccording to the Memorial Sloan Kettering Cancer Center nomogram (available at https://www.evidencio.com/models/show/440)

^bDuration from last SBRT to failure and management after failure

^cADT was administered for 2.3 months before SBRT and continued for 2.1 months after SBRT

^dADT was administered for 2.7 months before SBRT and continued for 1.3 months after SBRT

^eFollow-up loss for 1 year and 3 months after biochemical failure

Abbreviations: ADT, androgen deprivation therapy; BCF, biochemical failure; DF, distant failure; EOD, every-other-day; GS, Gleason score; LF, local failure; LN, lymph node; m, months; Mon., monitoring; S, surgery; PSA, prostate-specific antigen; PSADT, prostate-specific antigen doubling time; RF, regional failure; SBRT, stereotactic body radiotherapy; W/U, work-up; y, years

Both the 5- and 10-year local control rates were 100%, and the regional control rates were 97.3% (95% confidence interval [CI], 93.6–100.0) at both time points. The 5-year distant control rate was 97.4% (95% CI, 93.9–100.0), which decreased to 93.3% (95% CI, 86.9–100.0) at 10 years: bone (n = 5) and lymph nodes (n = 1) metastases. The 5- and 10-year OS rates were 97.4% (95% CI, 93.9–100.0) and 95.9% (95% CI, 91.4–100.0), respectively. However, no patients died due to prostate cancer.

The BCFFS rates were 89.9% (95% CI, 83.4–96.8) at 5 years and 86.3% (95% CI, 78.6–94.8) at 10 years (Fig. 1A). The 5- and 10-year BCFFS rates were both 90.5% (95% CI, 78.8–100.0) for the ≤ low-risk group, 90.5% (95% CI, 82.1–99.8) and 83.4% (95% CI, 71.8–97.0) for the intermediate-risk group, and both 85.7% (95% CI, 69.2–100.0) for the ≥ high-risk group, respectively, with no significant difference among groups (p = 0.870, Fig. 1B). Compared to the EOD group (5-year, 80.2% [95% CI, 67.1–95.7]; 10-year, 70.9% [95% CI, 55.3–90.9]), the daily treatment group showed consistently higher BCFFS rates at both 5 and 10 years (95.8%; 95% CI, 90.3–100.0; p = 0.006, Fig. 1C).

Fig. 1.

Biochemical failure-free survival rates. (A) Entire patients. (B) Stratified by risk group. (C) Stratified by treatment schedule. EOD, every-other-day

The 5- and 10-year CFFS rates were 92.2% (95% CI, 86.4–98.4) and 86.7% (95% CI, 78.8–95.4, Fig. 2A), respectively, for the total population. CFFS rates at 5 and 10 years were 95.2% (95% CI, 86.6–100.0) and 88.9% (95% CI, 75.3–100.0) for the ≤ low-risk group, 90.3% (95% CI, 81.8–99.8) and 87.2% (95% CI, 77.3–98.5) for the intermediate-risk group, and 92.9% (95% CI, 80.3–100.0) and 82.5% (95% CI, 62.8–100.0) for the ≥ high-risk group, respectively, with overlapping confidence intervals and no significant intergroup difference (p = 0.990, Fig. 2B). The PSA nadir (< 0.15 vs. ≥ 0.15 ng/ml) did not affect the CFFS (10-year, 85.0% [95% CI, 74.3–97.2] vs. 89.6% [95% CI, 79.1–100.0]; p = 0.580, Fig. 2C). The time to reach the PSA nadir (< 5 vs. ≥ 5 years) were associated with the CFFS. The 10-year CFFS rates were 77.3% (95% CI, 64.9–92.1) and 100% for patients with a time to PSA nadir of < 5 years and ≥ 5 years, respectively (p = 0.016, Fig. 2D).

Fig. 2.

Clinical failure-free survival rates. (A) Entire patients. (B) Stratified by risk group. (C) Stratified by the value of the prostate-specific antigen (PSA) nadir. (D) Stratified by the time to the PSA nadir

The median PSA nadir was 0.09 ng/ml (range, 0.0–3.12 ng/ml), with a median interval to PSA nadir of 52.8 months (range, 0.4–170.2 months). A significant negative correlation was observed between the PSA nadir and interval to the PSA nadir (r = −0.233, p = 0.035), as shown in Fig. 3. When stratified by risk group, the correlations were −0.386 (p = 0.084) for the ≤ low-risk group, −0.265 (p = 0.071) for the intermediate-risk group, and 0.126 (p = 0.667) for the ≥ high-risk group. Among the ≥ high-risk patients, those who did not receive ADT (n = 8) showed a marginally significant negative correlation (r = −0.672, p = 0.068), whereas no meaningful correlation was observed in those who received ADT (n = 6, r = 0.107, p = 0.840).

Fig. 3.

Association between the value of and interval to prostate-specific antigen nadir. PSA, prostate-specific antigen

The multivariate analysis confirmed daily treatment compared to EOD (hazard ratio [HR], 0.220; 95% CI, 0.067–0.720; p = 0.012) and an interval to PSA nadir of ≥ 5 years (HR, 0.120; 95% CI, 0.015–0.944; p = 0.044) as significant predictors of BCFFS and CFFS, respectively (Table 3). No other variables were associated with the BCFFS and CFFS.

Table 3.

Univariate analysis of prognostic factors for biochemical failure- and clinical failure-free survival

Variables	Biochemical failure-free survival		Clinical failure-free survival
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age ≥ 70 years	1.483 (0.493–4.457)	0.483	2.328 (0.678–7.996)	0.179
Initial PSA ≥ 9 ng/ml	2.789 (0.933–8.343)	0.067	1.764 (0.513–6.068)	0.368
PSA before SBRT ≥ 7 ng/ml	1.249 (0.418–3.730)	0.691	0.836 (0.244–2.864)	0.775
T stage ≥ 2c	0.317 (0.070–1.445)	0.138	0.717 (0.189–2.719)	0.625
Gleason score ≥ 7(4 + 3)	0.711 (0.158–3.208)	0.657	1.451 (0.384–5.488)	0.583
Risk group ≥ intermediate	1.300 (0.356–4.746)	0.691	1.066 (0.281–4.038)	0.925
Lymph node involvement riska ≥ 5%	0.796 (0.169–3.758)	0.773	1.510 (0.376–6.062)	0.561
ADT before SBRT	0.422 (0.054–3.264)	0.408	0.446 (0.056–3.547)	0.445
ADT after SBRT	0.441 (0.057–3.421)	0.433	0.464 (0.058–3.707)	0.469
Total dose 37.5 Gy	294,442,198 (0-inf)	0.998	3.326 (0.422–26.190)	0.254
Daily treatment	0.220 (0.067–0.720)	0.012	0.593 (0.176–1.996)	0.399
PSA nadir of ≥ 0.15 ng/ml	-	-	1.401 (0.427-4.600)	0.578
Interval to PSA nadir of ≥ 5 years	-	-	0.120 (0.015–0.944)	0.044

^aAccording to the Memorial Sloan Kettering Cancer Center nomogram (available at https://www.evidencio.com/models/show/440)

Abbreviations: ADT, androgen deprivation therapy; CI, confidence interval; HR, hazard ratio; PSA, prostate-specific antigen; SBRT, stereotactic body radiotherapy

Since the last follow-up of the previous study, no additional late GU or GI toxicity has occurred during the extended follow-up period [6]. Grade ≥ 3 late GU toxicity was not observed up to the last follow-up. Two patients (2.4%) experienced grade ≥ 3 late GI toxicity, and it resolved after appropriate management.

Discussion

This study represents one of the longest and most comprehensive analyses of robotic SBRT for LPC, with a median follow-up of 11.0 years. By closely analyzing PSA kinetics, including the time to reach the PSA nadir, we thoroughly evaluated the long-term treatment efficacy and prognostic markers of SBRT. Of particular interest, daily SBRT schedules were associated with superior biochemical control compared to EOD schedules. Our findings demonstrate excellent outcomes, marked by low rates of biochemical and local failure while maintaining a favorable toxicity profile.

Although a few have presented long-term data exceeding 5 years, the majority of studies on the treatment outcomes of SBRT for LPC have a median follow-up period of < 5 years, leading to a lack of sufficient long-term data in this field [11–14]. The results of our study provide long-term follow-up data that can enhance the understanding of SBRT efficacy and safety in the treatment of LPC. Of the 82 patients, BCF was observed in nine (11.0%), local recurrence in one (1.2%), regional recurrence in two (2.4%), and distant metastasis in five (6.1%). The 10-year local, regional, and distant control rates were 100%, 97.3%, and 93.3%, respectively, which were comparable to but slightly poorer than the findings of a previous study [13]. This may be attributed to the inclusion of 14 patients categorized as ≥ high-risk in our study.

Distinct from previous reports, this study provides detailed data on patients who experienced failure (Table 2), revealing several key insights. First, a significant proportion of failures, including BCF, occurred after 5 years, indicating that long-term follow-up is necessary. Second, some patients with BCF were followed up without additional treatment and showed no further recurrence. This casts doubt on the necessity of ADT after BCF and warrants further validation. Guidelines for BCR treatment emphasize risk-based approaches, with active surveillance for low-risk cases and early salvage therapies for high-risk cases [15]. Third, the relatively high rate of distant failure compared to local or regional failures suggests that early systemic imaging workups, including prostate-specific membrane antigen positron emission tomography/computed tomography, and ADT may benefit these patients, particularly those categorized as high-risk.

The 10-year BCFFS rate for all patients was 86.3%, with rates of 90.5%, 83.4%, and 85.7% for patients categorized as ≤ low-, intermediate-, and ≥ high-risk, respectively. The majority of studies on SBRT for LPC have focused exclusively on patients categorized as low- or intermediate-risk; however, this study included 14 ≥ high-risk patients and found no significant difference in BCFFS across risk groups (p = 0.870). The overall 10-year CFFS rate in the study was 86.7%, with no significant difference observed among the risk groups (88.9% for ≤ low-risk, 87.2% for intermediate-risk, and 82.5% for ≥ high-risk; p = 0.990). These outcomes may reflect the small sample size of ≥ high-risk patients combined with a low number of treatment failures.

Meanwhile, the SBRT treatment schedule significantly influenced BCFFS outcomes, with the daily regimen demonstrating superior long-term biochemical control. Although there is currently no established consensus on the optimal interval between SBRT fractions, and clinical practices vary depending on institutional protocols or physician preference, the observed advantage of daily treatment in this study may have important implications for future clinical practice. Supporting this notion, a previous study on stage I non-small cell lung cancer reported inferior overall survival with an EOD regimen compared to daily treatment in patients receiving five-fraction SBRT [16]. Interestingly, in the three-fraction setting, the same study found the opposite trend, suggesting that the larger fraction size associated with daily treatment may lead to increased toxicity, thereby compromising overall survival [16].

In conventional RT, PSA nadir values ranging from 0.2 to 1.5 ng/ml are commonly used as a predictive cut-off for treatment outcomes [17–19]. However, several studies have reported that patients treated with SBRT often achieve significantly lower PSA nadir levels than those treated with conventional RT [20, 21]. Given the enhanced PSA suppression observed with SBRT, we adopted a lower cut-off value of 0.15 ng/ml to better align with the unique treatment dynamics of SBRT. However, in the present study, PSA nadir did not significantly affect CFFS. This finding may offer meaningful insight, as most previous studies on PSA kinetics have focused on BCF as the primary endpoint [22, 23]. This may suggest that PSA nadir is more predictive of biochemical recurrence than of overt clinical progression, possibly due to its greater sensitivity in detecting early biochemical changes rather than late-stage clinical events.

In earlier analyses, it was observed that patients who reached the PSA nadir more than 2 years after treatment had better prognoses than those who reached the nadir earlier [6]. The present updated analysis yielded similar results, wherein a longer time to reach PSA nadir (≥ 5 years) was associated with improved outcomes. This supports the notion that a slower, more sustained decline in PSA levels may indicate a more robust and lasting treatment response. While the PSA nadir is reached rapidly after SBRT in some cases, a longer interval to PSA nadir was generally associated with a lower PSA nadir. According to a meta-analysis, SBRT demonstrated a rapid initial drop in PSA levels, gradually decelerating over time, ultimately achieving a lower nadir than that achieved with conventional RT [22]. The initial rapid decline in PSA levels is likely driven by the elimination of malignant cells, with the subsequent slower and more prolonged decrease attributed to a reduction in PSA production by benign epithelial tissues [20].

This study corroborates our previous findings, demonstrating that SBRT is well-tolerated with low rates of severe adverse events [6]. Even with an additional median follow-up of 5 years, no new late toxicities were observed, further reinforcing the safety profile of SBRT in this patient population. The absence of significant long-term toxicity highlights one of the key advantages of SBRT, making it an appealing treatment option, particularly for elderly patients or those with comorbidities who may face challenges tolerating longer RT regimens.

Our investigation, while informative, carries inherent methodological limitations. The retrospective design, modest sample size, and very low number of failure events introduce potential constraints in generalizing our results across broader clinical contexts, especially in analyses stratified by risk group. Moreover, the population included low-, intermediate-, and high-risk cases, which may obscure the nuanced clinical implications for low- and intermediate-risk cases.

Conclusions

Based on the study’s extensive 11-year follow-up period, robotic SBRT demonstrates exceptional long-term efficacy in treating LPC, achieving excellent biochemical control and impressive local control rates with minimal toxicity. Daily treatment schedules were associated with superior biochemical control, suggesting a potential practice-changing implication. The findings emphasize the critical prognostic value of PSA kinetics, showing that a time to nadir of ≥ 5 years are associated with improved treatment outcomes. Additionally, our findings suggest the importance of regular systemic imaging workups for enhanced long-term management. Together, these favorable outcomes establish robotic SBRT as a highly effective treatment option for LPC.

Abbreviations

ADT

Androgen deprivation therapy

BCF

Biochemical failure

BCFFS

Biochemical failure-free survival

CFFS

Clinical failure-free survival

CI

Confidence interval

DF

Distant failure

EOD

Every-other-day

GI

Gastrointestinal

GS

Gleason score

GU

Genitourinary

HR

Hazard ratio

LF

Local failure

LN

Lymph node

LPC

Localized prostate cancer

m

Months

Mon

Monitoring

OS

Overall survival

PSA

Prostate-specific antigen

PSADT

Prostate-specific antigen doubling time

PTV

Planning target volume

RF

Regional failure

RT

Radiotherapy

S

Surgery

SBRT

Stereotactic body radiotherapy

W/U

Work-up

y

Years

Author contributions

Conceptualization – ARC; Supervision – ARC; Data curation – JSK, YP, HJP, WIJ, BKJ, and HJK; Methodology – JSK; Formal analysis and visualization – JSK and ARC; Writing-original draft – JSK; and Writing-review and editing – JSK, YP, HJP, WIJ, BKJ, HJK, and ARC. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Soonchunhyang University Research Fund. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data availability

The datasets generated and/or analyzed during the study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Institutional Review Board of all participant institutions and conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was not required as the study involved a retrospective review with minimal risk to the participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.