Efficacy and Safety Analyses of Cytoreductive Non-Regional Lymph Node Radiotherapy in Addition to Prostate-Directed Local Therapy in Low Metastatic Burden Prostate Cancer

doi:10.21203/rs.3.rs-2442620/v1

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Efficacy and Safety Analyses of Cytoreductive Non-Regional Lymph Node Radiotherapy in Addition to Prostate-Directed Local Therapy in Low Metastatic Burden Prostate Cancer

https://doi.org/10.21203/rs.3.rs-2442620/v1

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Background

To evaluate the efficacy and safety of cytoreductive non-regional lymph node radiotherapy (NRLNRT) in addition to prostate-directed local therapy (PDLT) in low metastatic burden prostate cancer (LMBPC).

Methods

From August 2009 to February 2021, 88 LMBPC patients with NRLN metastasis were identified. Patients receiving cytoreductive NRLN RT in addition to PDLT (NRLN RT group) were matched by one-to-one propensity score to patients without cytoreductive NRLN radiotherapy (control group). Kaplan-Meier method and Cox proportional hazards model were used for prognostic analyses.

Results

The median follow-up was 43.3 months. PSA response after NRLN RT was 70.6%, and the median PFS after NRLN RT was 29.5 months. The 4-year OS for NRLN RT group and control group was 62% and 46%, respectively (P = 0.037). NRLN RT (HR 0.22, P = 0.001), HSPC (HR 0.32, P = 0.003), bone metastases (HR 3.79, P = 0.000) and androgen-receptor-axis-targeted agents (HR 0.40, P=0.007) were independent prognostic factors of OS. Subgroup analyses showed HSPC at the time of NRLNM and patients with ＜5 NRLNM had greater magnitude of benefit than the counterpart (HR 0.28, 95% CI 0.08-0.94, P= 0.039; HR 0.16, 95% CI 0.04-0.69, P = 0.014). After PSM, NRLN RT was still associated with improved OS (HR 0.39, 95% CI 0.16-0.96, P = 0.040). NRLN RT related AEs were 11 cases (32.4%) of acute gastrointestinal AEs, 3 cases (8.8%) of acute skin AEs, 10 cases (29.4%) of acute bone marrow suppression (BMS) and 5 cases (14.7%) of chronic BMS. All were grade 1-2 AEs.

Conclusions

It was beneficial and safe to apply cytoreductive NRLN radiotherapy in addition to PDLT in LMBPC. HSPC at the time of NRLNM and patients with < 5 NRLNM may be the potential beneficiaries. Prospective studies were needed for verification.

non-regional lymph node

metastatic prostate cancer

cytoreductive radiotherapy

low metastatic volume

Cytoreductive radiotherapy has risen widespread concern in the realm of metastatic prostate cancer (mPC). Prostate-directed radiotherapy (PDRT) can improve the overall survival of low metastatic volume hormone-sensitive prostate cancer (mHSPC)[1–3]. Metastatic-directed radiotherapy (MDRT) is associated with improved androgen deprivation therapy (ADT)-free survival and progression-free survival (PFS)[4] for oligometastatic patients who had previously received curative local therapy. It seems more reasonable to adopt the CHAARTED criteria to assess the survival benefits associated with extent of cytoreductive therapy in mPC[5]. Recently, the latest analyses from the STAMPEDE study show PDRT also benefit low metastatic burden prostate cancer (LMBPC) patients with only non-regional lymph nodes metastases (NRLNM)[6]. However, benefits of greater extent cytoreduction is yet to be studied in LMBPC, and what’s more, it leaves us another practical question that how to identify the best beneficiaries in this scenario.

Hence, this study focuses on LMBPC patients with NRLNM, analyzing the survival outcomes and prognostic factors, for the purpose of exploring the efficacy and safety of non-regional lymph node radiotherapy (NRLN RT) and finding potential beneficiaries in clinics.

Patient selection and baseline evaluation

This study was approved by the ethics committee of on Scientific Research Sun Yat-Sen University Cancer Center (IRB number: B2022-181). The medical records of 202 mPC patients with non-regional lymph nodes metastases at Sun Yat-Sen University Cancer Center between August 2009 and September 2022 were retrospectively analyzed. Patients with high metastatic volume according to the CHAARTED criteria, or complicated with other malignancies, or follow-up time < 6 months, or those with missing key clinical data were excluded, leaving a total of 88 mPC patients in the analysis.

High metastatic burden was defined as 4 bone metastases with one or more outside the vertebral bodies/pelvis or with visceral metastases. Low metastatic burden was defined as the metastatic burden without the condition of high metastatic volume. CRPC was defined as biochemical or radiological progression in patients receiving ADT with castrate serum testosterone levels (< 50 ng/dL) according to the Prostate Cancer Working Group 3 (PCWG3) criteria[7].

Treatment Approaches

For the patients who had previously received prostate-directed local therapy (PDLT) (prostate radiotherapy or prostatectomy), those with regional lymph node metastasis, pelvic lymph node dissection and/or radiotherapy were also applied. All of the patients received lifelong ADT (either orchiectomy or gonadotropin-releasing hormone agonist/antagonist) immediately after the diagnosis of metastasis.

Patients receiving cytoreductive NRLN radiotherapy in addition to PDLT were categorized into the NRLN RT group, leaving others to the control group. In NRLN RT group, all of the patients were stimulated by supine or prone position with contrast-enhanced computed tomography scans for radiotherapy planning. Contouring and prescribed dose were based on the recommendations by the Radiation Therapy Oncology Group (RTOG). Gross tumor volume (GTV) was defined as positive lymph nodes detected by imaging. The clinical target volume (CTV) included the gross primary tumor volume (GTV) with a radial margin of 0.5 cm and also covered the elective nodal regions. The planning target volume (PTV) was the CTV plus a uniform margin of 0.5 cm expansion. The typical radiation dose was 60 Gy for PGTV and 45Gy for PCTV in 25 fractions, once daily, 5 days a week. Prescription dose was required to cover more than 95% of the target lesion. Normal tissue constraints were based on RTOG. Intensity-modulated radiotherapy (IMRT) or volumetric intensity-modulated arc therapy (VMAT) was used for planning, and 6MV X-ray beams were generated by Elekta or Varian linear accelerator.

The application of androgen-receptor-axis-targeted agents (ARATAs) and chemotherapy (CT) were according to the clinical guidelines, patients’ wishes and drug accessibility. In the study, drug history was recorded after the diagnosis of NRLNM.

Outcome Evaluations

Outcome evaluations

The duration of follow-up was calculated from the time of diagnosis of NRLNM. In most cases, patients were regularly followed up every 3 months with a prostate-specific antigen (PSA) assessment, and radiological evaluation was arranged when the physician considered it necessary. Acute and late adverse events were assessed according to the Common Terminology Criteria for Adverse Events Version 4.0.

Overall survival (OS) was calculated from the time of diagnosis of NRLNM to the death due to any cause or the last follow-up. Progression-free survival (PFS) after NRLN RT was measured from the beginning of NRLN RT until PSA or radiographic progression. PSA response after NRLN RT was defined as a > 50% decline in serum PSA levels from the baseline before NRLN RT, according to PCWG3[7].

Statistical analysis

Data were summarized by descriptive statistics (using frequency for categorical variables and median with interquartile range (IQR) for continuous variables). Chi-Square test was used for comparing categorical data. Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test. Multivariate analysis was performed using Cox proportional hazards regression. Propensity score matching (PSM) was used to balance confounding factors. One-to-one matching without replacement was utilized using nearest-neighbor matching, with a caliper value of 0.2, taking PSA when NRLNM, Gleason score, castration status, number of bone metastases as covariates. A P value < 0.05 was considered statistically significant. Statistical analyses were performed with SPSS version 26.0 (IBM Corp., NY, USA) and the R statistical software (version 4.2.1).

Patient and disease characteristics

The study flow diagram was illustrated as Fig. 1. The baseline characteristics of 88 LMBPC patients with NRLNM after PDLT for analysis are shown in Table 1. There were 34 patients in NRLN RT group, while there were 54 patients in control group. The percentage of patient with a PSA < 20mg/ml at the time of NRLNM in NRLN RT group was higher than that in the control group (50% vs 20.4%, P = 0.004). No other significant difference was observed between 2 groups. The percentage of patients with ≥ 5 NRLNM in bone metastases group was significantly lower than that in those without bone metastases (29.3% vs 57.4%, P = 0.008). The percentage of CRPC at the time of NRLNM was higher in patients with chemotherapy than that in those without chemotherapy (56.0% vs 22.2%, P = 0.002). Of the 34 patients in NRLN RT group, 13 cases underwent NRLN RT concurrent with PDLT at metastatic stage, 12 cases received NRLN RT after PDLT at local stage and 9 cases had NRLN RT after PDLT at metastatic stage respectively.

Table 1

Baseline characteristics of the patients (N = 88)
	NRLN RT group (N = 34)			Control group (N = 54)	P
Median age at diagnosis (year) (IQR)	66(53–87)			65(45–91)	0.680
PSA (ng/mL) when NRLNM					0.004
< 20	17 (50)			11 (20.4)
≥ 20	17 (50)			43 (79.6)
Gleason score					0.698
≤ 8	14(41.2)			20(37)
9–10	20(58.8)			34(63)
HSPC at the time of NRLNM					0.065
No		16 (47.1)	15 (27.8)
Yes		18 (52.9)	39 (72.2)
Bone metastases					0.944
No		18 (52.9)	29 (53.7)
Yes		16 (47.1)	25 (46.3)
Site of NRLNM
Retroperitoneal involved		32 (94.1)	50 (92.6)		1.000
Others		2 (5.9)	4 (7.4)
No. of NRLNM					0.681
< 5		18 (52.9)	31 (57.4)
≥ 5		16 (47.1)	23 (42.6)
ARATAs
No		14 (41.2)	24 (44.4)		0.763
Yes		20 (58.8)	30 (55.6)
CT
No		24 (70.6)	39 (72.2)		0.869
Yes		10 (29.4)	15 (27.8)
PSA: prostate specific-antigen; NRLNM: non-regional lymph node metastases; HSPC: hormone-sensitive prostate cancer; ARATAs: androgen-receptor-axis-targeted agents; CT: chemotherapy.

Analysis Of Survival Outcomes, Psa Response And Prognostic Factors

After median follow-up of 43.3 months, 38 patients (43.2%) died leaving a total of 50 patients (56.8%) alive. 4-year OS was 46% and 62% in control group and NRLN RT group (Fig. 2A). Median NRLN RT-PFS was 29.5months. Among NRLN RT group, 70.6% of patients showed PSA response after NRLN RT. The largest PSA change was depicted as a waterfall plot shown in Fig. 2B.

In both univariate and multivariate analyses, NRLN RT together with HSPC at the time of NRLNM, bone metastases, and application of androgen-receptor-axis-targeted agents (ARATAs) were evaluated to correlate closely with OS (Table 2). Patients who underwent NRLN RT for metachronous disease had a tendency of better OS than those received NRLN RT for synchronous disease (P = 0.054, Fig. 2C).

Table 2

Univariate and multivariate Cox hazard analyses of prognostic factors for the overall survival
	Univariate
	HR	95% CI	P	HR	95% CI	P
Age (year)
< 65	1
≥ 65	1.41	(0.68–2.90)	0.358
PSA (ng/mL) at the time of NRLNM
< 20	1
≥ 20	1.48	(0.71–3.06)	0.296
Gleason score
≤ 8	1
9–10	1.01	(0.49–2.10)	0.978
HSPC at the time of NRLNM
No	1			1
Yes	0.49	(0.25–0.96)	0.038	0.32	(0.15–0.68)	0.003
Bone metastases
No	1			1
Yes	3.11	(1.60–6.03)	0.001	3.79	(1.88–7.62)	0.000
Site of NRLNM
Retroperitoneal involved	1
Others	1.303	(0.31–5.51)	0.719
No. of NRLNM
< 5	1
≥ 5	0.98	(0.52, 1.85)	0.940
ARATAs
No	1			1
Yes	0.36	(0.17–0.76)	0.007	0.40	(0.21–0.78)	0.007
CT
No	1
Yes	1.19	(0.55–2.55)	0.659
NRLN RT
No	1			1
Yes	0.38	(0.15–0.92)	0.032	0.23	(0.10–0.54)	0.001
PSA: prostate specific-antigen; NRLNM: non-regional lymph node metastases; HSPC: hormone-sensitive prostate cancer; ARATAs: androgen-receptor-axis-targeted agents; CT: chemotherapy; NRLN RT: non-regional lymph node radiotherapy.

After matching, 29 patients in NRLN RT group were matched to 29 patients in control group, and the baseline characteristics were balanced as summarized in Table 3. The median OS of NRLN RT group was significantly longer than that of control group (not reached vs 39.6 months, P = 0.033) (Fig. 2D).

Table 3

Baseline characteristics of the patients (N = 58)
		NRLN RT group(N = 29)	Control group (N = 29)	P
Median Age at initial Dx (year) (IQR)		65 (59–74)	64 (61–69)	0.803
PSA (ng/mL) at the time of NRLNM				0.594
< 20		13 (54.2)	11 (45.8)
≥ 20		16 (47.1)	18 (52.9)
Gleason score				0.588
≤ 8		10(34.5)	12(41.4)
9–10		19(65.5)	17(58.6)
HSPC at the time of NRLNM				0.421
No	13 (44.8)		10 (34.5)
Yes	16 (55.2)		19 (65.5)
Bone metastases				0.793
No	15(51.7)		14 (48.3)
Yes	14 (48.3)		15 (51.7)
Site of NRLNM				0.300
Retroperitoneal involved	28 (96.6)		26 (89.7)
Others	1 (3.4)		3 (10.3)
No. of NRLNM				0.185
< 5	14 (48.3)		19 (65.5)
≥ 5	15 (51.7)		10 (34.5)
ARATAs				0.426
No	14 (48.3)		11 (37.9)
Yes	15 (51.7)		18 (62.1)
CT				1.000
No	20 (69.0)		20 (69.0)
Yes	9 (31.0)		9 (31.0)
PSA: prostate specific-antigen; NRLN: non-regional lymph node; HSPC: hormone-sensitive prostate cancer.

Figure 3 showed a representative patient who diagnosed as M1a at first, received NRLN RT at mCRPC stage and had a long-term tumor control thereafter.

Subgroup Analyses Of Os

The analysis results of the influence of NRLN RT on OS in different subgroups was demonstrated in Fig. 4. The NRLN RT group was associated with improved OS in the subgroups of HSPC at the time of NRLNM, bone metastases, < 5 NRLNM and no chemotherapy. The benefit of NRLN RT was not evaluated in patients other than retroperitoneal involved according to the prognostic index given that there were only nine patients in this subgroup. NRLN RT was associated with a reduction of death of 84% (HR 0.16, 95% CI 0.04–0.69, P = 0.014) in the subgroup of < 5 NRLNM, while this benefit was not observed in patients with ≥ 5 NRLNM. OS advantages of NRLN RT was not observed in different subgroups of the age, PSA, Gleason score, site of NRLNM (retroperitoneal involved) or application of ARATAs.

Adverse Events Related To Nrln Rt

NRLN RT was well tolerated, with no grade 3 or higher toxicities reported (Table 4). Acute adverse events (AEs) included gastrointestinal (GI) toxicity (Grade 1: 9 patients, Grade 2: 2 patients), skin toxicity (Grade1: one patient, Grade 2: 2 patients) and bone marrow suppression (Grade 1: 4 patients, Grade 2: 6 patients). In regard to the late AEs, grade 1 and grade 2 late bone marrow suppression were observed in 2 and 3 patients, respectively.

Table 4

NRLN RT related adverse events
N (%)	Acute GI AEs	Acute skin AEs	Acute BMS	Late BMS
Grade 0	23(67.6)	31(91.2)	24(70.6)	29(85.3)
Grade 1	9(26.5)	1(2.9)	4(11.8)	2(5.9)
Grade 2	2(5.9)	2(5.9)	6(17.6)	3(8.8)
PSA: prostate specific-antigen; NRLNM: non-regional lymph node metastases; HSPC: hormone-sensitive prostate cancer; ARATAs: androgen-receptor-axis-targeted agents; CT: chemotherapy; NRLN RT: non-regional lymph node radiotherapy.

The value of PDRT in LMBPC has been widely accepted and written into different international acknowledged guidelines. However, whether a greater extent of cytoreduction is beneficial to LMBPC is yet to be confirmed. In the study, we focused on LMBPC patients with NRLNM, innovatively reported the efficacy and safety of NRLN RT in addition to PDLT, and found that HSPC and patients with ༜5 NRLNM may potentially benefit from NRLN RT.

It is interesting to find in our study that NRLN RT was evaluated as an independent prognostic factor for OS in LMBPC. After propensity-score matching to balance confounding factors, NRLN RT was also associated with improved OS in LMBPC. According to the latest results from STAMPEDE, PDRT is most beneficial for LMBPC patients with NRLNM only or those with ≤ 3 bone metastases[6]. Since greater extent of cytoreduction in addition to PDLT may improve clinical outcomes in mPC[5, 8–11], we think it is reasonable to think about cytoreductive RT for NRLN in selective LMBPC patients. Recently, Chopade et al. reported that oligometastatic common iliac-M1a could be treated with curative radiotherapy plus long-term ADT and yielded a 5y OS of 90.1% as high as those with cN1. The result of our study also suggested that under the condition of primary tumor being controlled, NRLN RT could further decrease 54% of death risk in LMBPC with NRLNM. Similarly, in other malignancies, for example, in advanced cervical cancer, it has also been reported that retroperitoneal lymph nodes irradiation in addition to primary-site radiotherapy significantly decreased the recurrence of para-aortic lymph nodes as well as distant metastases compared to primary-site radiotherapy alone[12, 13]. Taking together, these data indicated that NRLN RT in addition to PDLT might delay disease progression and improve survival in selective cancer patients, including LMBPC patients with NRLNM.

When it comes to the question who would be most likely to benefit from NRLN RT, our results show that HSPC at the time of NRLNM and patients with ༜5 NRLNM may be the potential beneficiaries. It has been well accepted that cytoreductive RT is most helpful when mPC patients are still hormone sensitive. We found that applying cytoreductive NRLN radiotherapy in addition to PDLT in LMBPC resulted in a significant high death risk reduction for HSPC subgroup but not in CRPC patients. This indicates that a controllable disease stage is an important prerequisite for the benefit of cytoreductive RT. Secondary, tumor burden is another issue we should also concern about. It has been reported that nodal burden is a prognostic biomarker for patients with NRLNM[14]. In our study, we found NRLN RT significantly benefited LMBPC patients with ༜5 NRLNM but not the counterparts. It is also worth mentioning that the subgroup analyses seem to show patients with bone metastases obtained significant OS benefit from NRLN RT than those without bone metastases. We think it may at least partly attribute to less amount of NRLNM in patients with bone metastases in our study (70.7% vs 42.6%, P = 0.008). Additionally, we found that those patients who received cytoreductive NRLN RT for metachronous disease was more likely to gain survival benefit than other patients (P = 0.054), which was in line with the findings of Sweeney et al.[15] that metachronous disease had better prognosis than men with synchronous metastatic disease. But the P value in our study was marginal, further study with larger sample size are needed. In a word, our results suggested that NRLN RT may be beneficial to LMBPC patients who are hormone-sensitive and with a number of NRLNM less than 5.

Generally, it is safe to implement NRLN RT for LMBPC patients. AEs related to NRLN RT were relatively controllable and tolerable, mainly manifested as grade 1–2 toxic effects and without serious early or late side effects. Gastrointestinal (GI) toxicity is the most common side effect. It was reported that para-aortic lymph nodes irradiation regardless of prophylactically or therapeutic purpose, had only 3.9% incidence rate of grade 3 duodenal toxicity [16]. In another study, the incidence rate of grade 2 acute vomiting and nausea were only 13.3% and 6%, respectively [17], which was in accordance with our present results. Bone marrow suppression is another toxicity we are concerned about. Apart from NRLN RT, several other factors for instance, previous and concurrent medical prescription, history of pelvic radiotherapy, can also lead to bone marrow suppression. In our study, 29.4% of the patients presented with mild bone marrow suppression, half of which were recoverable.

We concede that our study has several limitations on its generalizability. Firstly, the retrospective study with a small amount of sample is an inherent shortcoming. However, given the lack of evidence on the role of further cytoreductive NRLN RT in addition to PDLT in LMBPC, our study still provides some valuable information for current practice. Secondly, our patients represent a heterogenous cohort of LMBPC patients who received different treatments at different time points. Thirdly, imaging modalities to assess the tumor burden could not be unified. Therefore, further studies are need to be validated our results. In current time, we could expect results from a trial (ISRCTN36344989) shedding light upon the value of para-aortic lymph nodes radiotherapy in mHSPC.

NRLN RT, together with HSPC, ARATAs and bone metastases were independent prognostic factors for LMBPC with NRLNM. It was beneficial and safe to apply cytoreductive NRLN RT in addition to PDLT in LMBPC. LMBPC patients who are hormone-sensitive and with a number of NRLNM less than 5 may be the potential beneficiaries. Further studies were needed to identify the precise indications.

ADT: androgen deprivation therapy

AEs: adverse events

ARATAs: androgen-receptor-axis-targeted agents

BMS: bone marrow suppression

CI: confidence interval

CT: chemotherapy

CTV: clinical target volume

GI: gastrointestinal

GTV: Gross tumor volume

HR: hazard ratio

IMRT: intensity-modulated radiotherapy

IQR: interquartile range

LMBPC: low metastatic burden prostate cancer

mCRPC: metastatic castration-resistant prostate cancer

MDRT: metastatic-directed radiotherapy

MDT: metastasis-directed therapy

mHSPC: metastatic hormone-sensitive prostate cancer

mPC: metastatic prostate cancer

NRLNM: non-regional lymph nodes metastases

NRLN RT: non-regional lymph node radiotherapy

PCWG3: Prostate Cancer Working Group 3

PDLT: prostate-directed local therapy

PDRT: prostate-directed radiotherapy

PET-CT: positron emission tomography-computed tomography

PFS: progression-free survival

PSA: prostate-specific antigen

PSM: propensity score matching

PSMA: prostate-specific membrane antigen

PTV: planning target volume

TURP: transurethral resection of prostate

VMAT: volumetric intensity-modulated arc therapy

Ethics approval and consent to participate

This manuscript was approved by the Ethics Committee on Scientific Research of Sun Yat-Sen University Cancer Center (IRB number: B2022-181).

Consent for publication

Written, informed consent was obtained for open access publication of this article from the patient described.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was supported by the National Natural Science Foundation of China (No. 82102988 and 81772483) and the Medical Research Foundation of Guangdong Province (No. A2022492).

Authors' contributions

LXM and RQL collected the patient’s information and drafted the manuscript. QWP and LLC participated in pathology review and performed the IHC staining of the biopsy. WFC, SJH, MSL collaborated in the treatment for this patient. YHL and FJZ collaborated in revision of the manuscript. LRH and LY conceived the study and participated in its coordination. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Author information

Lixin Mai, Ruiqi Liu, Qiwen Pan contributed equally to this work.

Affiliations

Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China

Lixin Mai, Ruiqi Liu, Qiwen Pan, Lingling Cai, Wufei Cao, Sijuan Huang, Maosheng Lin, Yang Liu, Liru He

Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Lixin Mai

Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China

Yonghong Li, Fangjian Zhou

Corresponding author

Correspondence to Liru He and Yang Liu.

Burdett S, Boeve LM, Ingleby FC, Fisher DJ, Rydzewska LH, Vale CL, et al. Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis. Eur Urol. 2019;76(1):115–24.
Boeve LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, 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):410–8.
Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. The Lancet. 2018;392(10162):2353–66.
Radwan N, Phillips R, Ross A, Rowe SP, Gorin MA, Antonarakis ES, et al. A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE). BMC Cancer. 2017;17(1):453.
Zhang Z, Wei M, Mai L, Li Y, Wu J, Huang H, et al. Survival Outcomes and Prognostic Analysis Following Greater Cytoreductive Radiotherapy in Patients With Metastatic Prostate Cancer. Front Oncol. 2020;10:549220.
Ali A, Hoyle A, Haran AM, Brawley CD, Cook A, Amos C, et al. Association of Bone Metastatic Burden With Survival Benefit From Prostate Radiotherapy in Patients With Newly Diagnosed Metastatic Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2021;7(4):555–63.
Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402–18.
Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, 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):650–9.
Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, 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):446–53.
Bravi CA, Fossati N, Gandaglia G, Suardi N, Mazzone E, Robesti D, et al. Long-term Outcomes of Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Not as Good as Previously Thought. Eur Urol. 2020;78(5):661–9.
Glicksman RM, Metser U, Vines D, Valliant J, Liu Z, Chung PW, et al. Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis. Eur Urol. 2021;80(3):374–82.
Sapienza LG, Gomes MJL, Calsavara VF, Leitao MM Jr, Baiocchi G. Does para-aortic irradiation reduce the risk of distant metastasis in advanced cervical cancer? A systematic review and meta-analysis of randomized clinical trials. Gynecol Oncol. 2017;144(2):312–7.
Jensen LG, Hasselle MD, Rose BS, Nath SK, Hasan Y, Scanderbeg DJ, et al. Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin. Int J Gynecol Cancer. 2013;23(1):119–25.
Haran ÁM, Jain Y, Hambrock T, Murphy LR, Cook A, Brown LC, et al. 1359MO Differential treatment response with nodal metastases in metastatic hormone-sensitive prostate cancer (mHSPC) and evaluation of nodal (N) burden as a prognostic biomarker: Ancillary studies of the docetaxel and abiraterone acetate and prednisolone (AAP) phase III trials from STAMPEDE. Ann Oncol. 2022;33:1161–S2.
Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy. Eur Urol. 2021;80(3):275–9.
Xu KM, Rajagopalan MS, Kim H, Beriwal S. Extended field intensity modulated radiation therapy for gynecologic cancers: Is the risk of duodenal toxicity high? Pract Radiat Oncol. 2015;5(4):e291–7.
Ballari N, Rai B, Bahl A, Mittal BR, Ghoshal S. Prospective observational study evaluating acute and delayed treatment related toxicities of prophylactic extended field volumetric modulated arc therapy with concurrent cisplatin in cervical cancer patients with pelvic lymph node metastasis. Tech Innov Patient Support Radiat Oncol. 2021;17:48–56.

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Efficacy and Safety Analyses of Cytoreductive Non-Regional Lymph Node Radiotherapy in Addition to Prostate-Directed Local Therapy in Low Metastatic Burden Prostate Cancer

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Abstract

Figures

Introduction

Methods

Patient selection and baseline evaluation

Treatment Approaches

Outcome Evaluations

Statistical analysis

Results

Patient and disease characteristics

Analysis Of Survival Outcomes, Psa Response And Prognostic Factors

Subgroup Analyses Of Os

Adverse Events Related To Nrln Rt

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1