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Review

SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer

by
Haitham Shaheen
1,2,*,
Mack Roach 3rd
3 and
Eman Essam Elsemary
1
1
Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
2
Swansea Bay University Health Board (SBUHB), Swansea SA12 7BR, UK
3
Radiation Oncology and Urology, Particle Therapy Research Program & Outreach, Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143-1708, USA
*
Author to whom correspondence should be addressed.
Soc. Int. Urol. J. 2025, 6(3), 46; https://doi.org/10.3390/siuj6030046
Submission received: 30 November 2024 / Revised: 23 February 2025 / Accepted: 25 February 2025 / Published: 13 June 2025
Browse Figure
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Abstract

:
Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents.

1. Introduction

With advancements in imaging modalities, localized prostate cancer with nodal involvement is increasingly treated now as a locoregional spread of prostate cancer rather than a systemic disease.
Uniquely, for prostate cancer, there are numerous nomograms based primarily on prostate-specific antigen (PSA) levels, Gleason score (GS), clinical stage, and sometimes the percentage of positive biopsies to predict the probability of pelvic nodal metastasis according to risk stratification, which physicians can use to select patients for prophylactic nodal treatment when their risk exceeds a certain level (e.g., ≥15%) [1,2].

The Definition of Positive Lymph Nodes

The definition of positive lymph nodes in prostate cancer is grouped into three categories:
  • Pathologically positive (pN+) lymph node metastasis, confirmed by pathology after Pelvic Lymph Node Dissection (PLND), which is considered the standard of care (SOC) for the diagnosis of positive lymph node disease in prostate cancer, or in rare cases, through nodal sampling;
  • Clinically positive (cN+) lymph node metastasis suggested by imaging, with the advent of new nuclear imaging techniques, improves identification in this category. Unfortunately, despite these advances, up to one-third of lymph node metastases are still missed;
  • Clinically negative (cN−) patients with high-risk features for lymph node involvement (LNI) can be readily identified using a host of validated formulas and nomograms.

2. Management of Pelvic Lymph Node Involvement

The selection of treatment modality for pelvic nodal involvement of prostate cancer is influenced by the management approach chosen for the primary tumors:
  • In patients undergoing radical prostatectomy (RP), surgical options include either PLND or Extended Pelvic Lymph Node Dissection (ePLND);
  • When radiation is the main treatment modality, whole pelvic radiotherapy (WPRT) with or without a nodal boost is considered the standard of care.
(a)
Surgical staging management

2.1. PLND vs. ePLND

The European Association of Urology (EAU) guidelines recommend ePLND for accurately staging the pelvis in patients with clinically confined prostate cancer (PCa) with a risk of nodal metastasis greater than 7% [3]. According to the American Urological Association (AUA) guidelines, PLND is advised for all patients at medium to high risk of nodal metastasis [4].
Fossati et al. [5] classified PLND into four types:
  • Limited PLND (LPLND): Involves the obturator nodes;
  • Standard PLND (SPLND): Involves the obturator and external iliac nodes; as shown in Figure 1
  • ePLND: Involves the obturator, external, and internal iliac nodes;
  • Super-extended PLND (SePLND): Encompasses ePLND plus common iliac, presacral, and/or other nodes.
The oncologic benefits of PLND for prostate cancer remain controversial, particularly due to the increased risks and complications associated with ePLND. While ePLND is more accurate in detecting metastatic lymph node involvement, it may not improve the oncologic outcomes and is associated with an increased risk of complications, particularly lymphocele.
Although in general, the surgical management of node-positive disease has been rather disappointing, it is now understood that in selected patients, more favorable outcomes have been reported, and surgical management appears to be feasible in reducing morbidity without compromising efficacy in patients undergoing unilateral resection of nodes, provided they have only unilateral disease as identified by prostate-specific antigen membrane positron-emission tomography (PSMA PET) [7,8,9].
An overview of the available guidelines for managing N1 disease is shown in Table 1.
(b)
Nonsurgical management: (radiation therapy + systemic treatment):
1.
Non-surgical management for patients with clinically node negative (cN0) at High Risk of lymph node metastasis (LNM) (i.e., Elective Nodal Irradiation)
For most solid tumors, prophylactic lymph node irradiation is considered a standard of care; however, in high-risk prostate cancer, it remains debatable practice with no universal consensus. Table 2 summarizes selected trials comparing prophylactic elective nodal irradiation (ENI) with prostate-only radiotherapy (PORT).
A significant part of this controversy comes from the misconception among many physicians that two randomized controlled trials (Radiation Therapy Oncology Group [RTOG] 9413 and French Genitourinary Study Group [GETUG] 01) yielded “negative” results in terms of both biochemical failure-free survival (BFFS) and overall survival (OS). In reality, no trials have demonstrated definitively “negative” results for “prophylactic pelvic nodal radiotherapy”. Notably, the GETUG—01 trial did not actually use “whole pelvic” radiotherapy (but rather treated only the “true pelvis”) as defined by the RTOG. Additionally, it included too many low-risk patients and was far too small a study to assess any clinically meaningful endpoints [13].

2.1.1. GETUG-01

Pommier et al. studied 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma randomized to receive either pelvic node and prostate or prostate-only radiation therapy. Patients were stratified into two groups: “low risk” (T1–T2, Gleason score 6, and PSA < 3× the upper limit of normal [ULN] of the laboratory) (92 patients) versus “high risk” (T3, Gleason score > 6, or PSA > 3× the ULN of the laboratory).
The investigators concluded that at a median follow-up of 11.4 years, the 10-year OS and event-free survival (EFS) were similar in the two treatment arms [14].

2.1.2. RTOG 9413

This study enrolled 1323 patients with a risk of LNI > 15% to evaluate the efficacy of WPRT versus PORT and to compare short-term neoadjuvant with adjuvant plus concurrent hormone therapy (HT), with the primary endpoint of progression-free survival [PFS] [18].
2.
Non-surgical management for patients with cN + ve disease in the primary setting: Radiotherapeutic options
Pelvic lymph node metastasis is a strong predictor of systemic spreading, and thus we typically recommend a combination of systemic and local-regional radiotherapy. This recommendation is partly supported by an early report by Granfors et al. and by the more recent Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) trial results [19,20].
The inadequacy of androgen deprivation therapy (ADT) alone has been evaluated in patients with locally advanced PCa in a randomized phase 3 trial conducted by the Scandinavian Prostate Cancer Group (SPCG). The SPCG-7 study showed that combining prostate radiotherapy with long-term hormone therapy was superior to long-term hormone therapy alone in terms of overall survival [21,22].
Table 3 summarizes the results of selected studies focusing on patients with N + M0 prostate cancer.

3. Nodal Irradiation: Simultaneous Integrated Boost (SIB) and Hypofractionation

Based on previous evidence, WPRT combined with ADT is now considered the standard of care in clinically positive nodal prostate cancer. With the advent of modern biological imaging techniques, such as prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT), it is likely that pelvic nodes will be detected earlier and more frequently. One efficient approach to treat node-positive disease with higher doses than uninvolved nodal areas is using a SIB to PSMA (prostate-specific membrane antigen)-positive nodes.
Onishi et al. [45] retrospectively analyzed 97 patients with clinically node-positive (cN1) prostate cancer who received intensity-modulated radiation therapy with SIB (SIB-IMRT). The investigators demonstrated favorable 5-year outcomes with low incidences of toxicity.
Recently, Basu et al. reported their findings on 22 patients with National Comprehensive Cancer Network (NCCN) high-risk (HR), N+, and oligometastatic (OM) PCa staged using prostate MRI and PSMA PET-CT who received SIB-SBRT (stereotactic body radiation therapy) [46]. The investigators found that SIB-SBRT for HR, N+, and OM prostate cancer achieved good biochemical control with minimal grade 3 toxicity.
Mizowaki et al. reported their experience with 52 patients with T2a-T4N1M0 prostate cancer, who were definitively treated with whole pelvis (WP) SIB-IMRT. The investigators reported very promising results, with excellent biochemical recurrence-free survival (bRFS), distant metastasis-free survival (MFS), OS, and prostate cancer-specific survival rates (PCCS) (69%, 78%, 88%, and 92%, respectively) at 5 years. In addition, the 5-year cumulative incidence rates for grade 2–3 late genitourinary (GU) and gastrointestinal (GI) toxicities were both 2%, with no grade 4 acute or late toxicity [47].

4. Patients with pN1 Disease in the Postoperative Setting

The EAU guidelines consider ePLND the standard of care and the most accurate staging procedure after RP, despite advancements in molecular imaging techniques [10]
Several retrospective studies recommend adding postoperative WPRT to ADT [40,48] especially for patients with between two and four positive nodes after nodal dissection [49]. These studies suggest that both PCSS and OS are improved when ADT is combined with WPRT compared with ADT alone [41,49,50]. However, to date, no randomized controlled study has explicitly tested the role of adjuvant radiotherapy (RT) in node-positive patients after RP and ePLND.

5. The Postoperative Salvage Setting: N + ve Disease

Salvage radiotherapy is the only curative treatment in the setting of biochemical recurrence after prostatectomy and no evidence of distant metastasis [51,52]. As pelvic nodes are among the most common sites of recurrence after RP, WPRT is almost a standard of care in the salvage setting and is supported by numerous prospective and retrospective trials [51,52,53].

6. The Case for Nodal Recurrence (rN + ve) Patients

ADT is generally considered a gold standard in patients with nodal recurrences after primary treatment for prostate cancer [24,54]. Emerging evidence supports the use of radiation therapy in oligorecurrent nodal disease, especially when combined with molecular imaging for localization of nodal recurrences.

7. SBRT in Oligometastatic Nodal Recurrence

Oligorecurrent (or “metachronous” oligometastatic) disease typically shows better outcomes than synchronous oligometastases, likely due to its more indolent biology and more lymphotropic pattern of recurrence [55].
Clinical evidence suggests that patients who develop metastases after 2 years or more of the treatment of the primary tumor tend to have better survival rates compared to those with early recurrence, indicating slower growing.
Although no level I evidence from phase 3 randomized trials exists specifically for oligometastatic prostate cancer, several prospective phase 1 and 2 clinical trials support the use of SBRT in this setting [56,57].
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) was the first phase 2 randomized trial to show a significant benefit in OS and PFS for SBRT combined with SOC compared with SOC alone, a benefit that persists with a long-term follow-up (8 yr OS, 27.2% vs. 13.6%; 8 yr PFS, 21.3% vs. 0.0%) [58]. This trial has been criticized for including only 16 patients with PCa, 14 of whom received SBRT.
Table 4 summarizes selected phase 2 clinical trials, Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP) and Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE), which provided the best “proof-of-principle” evidence supporting the use of SBRT in oligorecurrent disease.
The long-term outcomes of pooled data from both trials have been published [64]. With a median follow-up time of 52.5 months for the entire group, metastasis-directed therapy (MDT) remained associated with improved PFS compared to observation (pooled HR, 0.44; 95% CI, 0.29–0.66; p = 0.001). Interestingly, the PFS beyond 4 years was 15–20% with SBRT, suggesting that a good number of patients will benefit from a durable response with MDT. Although a further follow-up is needed, these encouraging results indicate that in appropriately selected patients, MDT (and specifically SBRT) without systemic therapy might be an alternative approach in well-informed patients wishing to avoid the side effects of ADT.
Also, it should be noted that despite the significant result of the ORIOLE trial, it had only four patients, emphasizing its potential impact on the generalizability of the study’s conclusions.
It seems reasonable to suggest that if the primary goals of SBRT in nodal oligorecurrent PCa are to achieve local control, prevent further metastasis, and delay subsequent systemic treatment escalation in selected patients, we should define our endpoints accordingly. A relevant issue that deserves further investigation is whether metastases-free survival, as measured by conventional imaging, can also act as a proxy for overall survival in patients with hormone-sensitive oligorecurrent PCa detected through molecular imaging.

8. Combined RT and Systemic Therapy

Some authors have investigated the use of MDT without ADT, despite being the current SOC for nodal oligorecurrence [65].
The results of these studies suggest that this approach could be a reasonable option in well-selected subgroups of patients in whom the main objective is to delay the effects of androgen suppression. However, the omission of ADT may compromise long-term survival [66].
Preclinical studies suggest that the synergistic effects and anti-neoangiogenic effects of ADT may contribute to normalizing irradiation and oxygenation of the tumor microenvironment, thereby enhancing the effectiveness of RT [67,68,69]. Deprivation therapy (DT) clearly plays a role in controlling distant micrometastasis and, consequently, reduces the risk of distant failure and improves outcomes in oligorecurrent disease [67,68,69].

9. Volume of Treatment and RT Scheme: SBRT vs. Elective Nodal Radiotherapy (ENRT)

It can be argued that using generous lymph node coverage, like ENRT with an additional SBRT boost, can reduce the likelihood of subsequent pelvic nodal recurrences and thus improve outcomes compared to SBRT alone. Although there is no prospective randomized trial conclusively defining the optimal radiotherapy strategy in oligo-nodal recurrence, available evidence for the use of ENRT is derived from retrospective and nonrandomized prospective studies, with wide variability in radiotherapy doses and schedules.
The Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) study, a randomized trial designed to compare both strategies, in addition to a 6-month regimen of ADT, has reported preliminary results indicating similar toxicity profiles, though the final results are awaited to assess differences in PFS [70]. Therefore, there remain unanswered questions regarding
  • Localized treatment (SBRT) or more extensive radiotherapy (ENRT);
  • The combination of these radiotherapies with ADT and/or androgen receptor pathway inhibitors (ARPIs);
  • The optimal timing and duration of such treatments.
The “standard of care” for these patients who experience a recurrence in non-regional nodes is the combination of ADT and ARPIs without local therapy. However, recent data have shown definitive radiotherapy in combination with limited ADT is likely to be a more effective strategy.

10. Ongoing Trials and Future Directions

The number of metastases detected on prostate-specific antigen membrane positron-emission tomography (PSMA-PET) currently serves as the selection criterion for the indication of MDT in PCa [71]. Some patients, particularly those who have not received systemic treatment, experience rapid widespread metastatic progression. Fortunately, there is increasing interest in investigating biomarkers that could help identify and select which patients would benefit from treatment intensification [72].
Ongoing trials are exploring the efficacy of MDT combined with ADT and/or androgen receptor signaling inhibitors (ARSIs), using an intermittent approach instead of a continuous one. This approach has the advantage of providing treatment breaks from hormonal manipulation, which positively impacts patient quality of life (QoL) while potentially preventing or delaying the development of widespread metastases [73].

11. Toxicity of Radiotherapy

  • Late GU toxicity: Theoretically, whole pelvic radiotherapy may increase toxicity compared with prostate-only radiotherapy [74]. There are discrepancies among studies regarding how much late GU toxicity there is, with some studies using advanced technologies reporting no significant difference in late GU toxicity with PORT versus WPRT at an intermediate dose [75,76,77,78]. In contrast, another study found a 40% increase in late GU toxicity with WPRT [16]
  • Late GI toxicity: Similar inconsistencies exist with late GI toxicity. Although the GETUG-01 trial [14] did not report any excess late GI toxicity, the RTOG 9413 trial [13] found significantly worse GI toxicity with WPRT versus PORT (5.1% vs. 1.9%). Tharmalingam and colleagues confirmed this significant increase in late GI toxicity (≥grade 2) [16]. However, both studies involved patients treated before the routine use of 3D conformal EBRT.
  • Hematological toxicity: Data on hematological toxicity are limited, and there were few ≥ grade 3 toxicities reported in the RTOG 9413 trial [13]. WPRT can result in lower absolute lymphocyte and white blood cell counts from baseline 1 year after treatment, particularly in smokers and in patients with low baseline lymphocyte counts. In such cases, the volume of ilium bone marrow receiving 40 Gray is a strong predictor of developing late lymphopenia [77]. WPRT increased late ≥grade 2 hematological toxicities, although absolute numbers remained low (29 [5%] of 570 patients) compared to prostate bed radiotherapy (27 [2%] of 1125 patients) [53]. Patient-reported toxicity scoring indicated more frequent bowel movements, loose stools, fecal urgency, and gas passage with WPRT [74].

12. Impact of Using Modern Radiotherapy Techniques on Toxicity

Advanced radiotherapy techniques appear to decrease both acute and late toxicity compared to traditional techniques. In general, trials using intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) report very low rates of severe toxicity, even when applying higher doses to the pelvis [16,74].
This is evident in the Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT) trial as it found a doubling of late GU toxicities, which is associated with the higher doses to the pelvis. However, no toxicities higher than grade 4 occurred, and grade 3 toxicities occurred in less than 2% of the patients (2 of 112), regardless of the treatment group [15] This low rate of ≥grade 3 toxicities has been confirmed by other studies.
Dosimetric studies showed that intensity-modulated proton therapy significantly reduces the dose to the bladder, small bowel, large bowel, and rectum compared with volumetric arc therapy [15]. However, it is still unclear whether these dosimetric advantages translate into meaningful clinical benefits in terms of reduced late toxicity. A registry study involving patients treated with pelvic proton therapy showed that intestinal and urinary toxicities were infrequent after a short follow-up of 14 months [75].

13. Additional Systemic Treatment

Combining ADT with docetaxel or second-generation hormone treatment is well established in the metastatic PCa setting [79,80]. Recently, these drugs have been studied in nonmetastatic PCa, demonstrating promising results [81].
Three trials—the STAMPEDE platform protocol, the NRG Oncology/RTOG 0512 trial, and the GETUG-12 trial—investigated the effect of adding adjuvant docetaxel to ADT. The studies found that adjuvant docetaxel combined with ADT prolonged time to relapse but not MFS or OS.

14. Conclusions

There are growing reasons for optimism about the management of node-positive prostate cancer. With advancements in therapeutic strategies, we are now better equipped to define patients at risk and balance the risks and benefits of aggressive treatment for this population of patients.

Author Contributions

Conceptualization, H.S. and M.R.3rd; methodology H.S. and M.R.3rd, software, H.S. and M.R.3rd; validation, H.S. and M.R.3rd; formal analysis, H.S. and M.R.3rd; investigation, H.S. and M.R.3rd; resources, H.S. and M.R.3rd; data curation H.S. and M.R.3rd; writing—original draft preparation, H.S. and M.R.3rd; writing—review and editing, H.S., M.R.3rd and E.E.E. visualization, H.S., M.R.3rd and E.E.E. supervision, M.R.3rd. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of this review.

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Siuj 06 00046 g001
Figure 1. (a) Anatomical extent of classical extended pelvic lymphadenectomy (PLND) encompassing the nodes along the major pelvic vessels including the internal iliac, external iliac and obturator regions to the iliac bifurcation (yellow and orange areas). (b) Anatomical extent of proposed (new) extended PLND by Matti and colleagues extending along the common iliac vessels to the ureteric crossing (pale red area). From Mattei et al. [6].
Figure 1. (a) Anatomical extent of classical extended pelvic lymphadenectomy (PLND) encompassing the nodes along the major pelvic vessels including the internal iliac, external iliac and obturator regions to the iliac bifurcation (yellow and orange areas). (b) Anatomical extent of proposed (new) extended PLND by Matti and colleagues extending along the common iliac vessels to the ureteric crossing (pale red area). From Mattei et al. [6].
Siuj 06 00046 g001
Table 1. Overview of available guidelines for management of N+ prostate cancer:
Table 1. Overview of available guidelines for management of N+ prostate cancer:
Guideline cN1M0 pN1M0
EAU [10]1. Offer local treatment (either RP or EBRT) and long-term ADT
2. Offer EBRT for prostate and pelvis in combination with long-term ADT and 2 years of abiraterone 		1. Offer adjuvant ADT
2. Offer ADT + EBRT
3. Offer observation (expectant management) after LND if ≤ 2 nodes and PSA < 0.1 ng/mL
FROGG [11]1. Pelvis and prostate EBRT and long-term ADT 1 Individualized discussion of observation, ADT, or EBRT + ADT
2 Patients should be referred to a radiation oncologist to discuss EBRT + ADT
NCCN [12]1. EBRT and ADT
2. EBRT, ADT, and abiraterone
3. ADT and abiraterone
4. If <5 years expected survival and asymptomatic: Observation or ADT 		1 ADT
2 EBRT + ADT 3 Observation
Abbreviations: cN1M0 patients: patients with clinically node-positive disease determined via any imaging modality; pN1M0 patients: patients with pathologically node-positive disease in postoperative setting either after initial treatment with radical prostatectomy (RP) and lymph node dissection (LND) or after staging LND; ADT: androgen deprivation therapy; EAU: European Association for Urology; EBRT: external beam radiotherapy; FROGG: Faculty of Radiation Oncology Genito-urinary Group; NCCN: National Comprehensive Cancer Network; PSA: prostate specific antigen.
Table 2. RCTs studied WPRT in cN0 disease in the primary setting evaluating prophylactic nodal radiotherapy.
Table 2. RCTs studied WPRT in cN0 disease in the primary setting evaluating prophylactic nodal radiotherapy.
Study DesignNo. of PtsLNI RiskTreatment GroupsOutcome
RTOG 9413 [13]RCT1322All > 15% (roach formula)2 × 2 design, Neoadjuvant ADT vs. adjuvant ADT–WPRT vs. PORTThe best PFS seen in patients with WPRT was in GS 7–10, PSA < 30 ng/mL, and Gleason score < 7 and PSA > 30 ng/mL
GETUG-01 trial [14]RCT44645% of pts > 15%WPRT vs. PORT—4–8 mo of ADTNo difference in 10 yr OS and EFS. A higher but non-WPRT has better EFS in the low-risk subgroup (77.2% vs. 62.5%; p = 0.18)
POP-RT trial [15]RCT224All > 20% (roach formula)WPRT vs. PORT—24 mo of ADTFavors WPRT: 5-yr BFFS was 95.0% with WPRT versus 81.2% with PORT, (HR) of 0.23 p < 0.0001). WPRT 5-yr DFS (89.5% vs. 77.2%; HR, 0.40; p = 0.002), 5 yr OS no differrence HR, 0.92; p = 0.83)
Tharmalingam et al. [16]Cohort812Not specifiedWPRT vs. PORT (with brachytherapy boost)—variable ADTFavors WPRT: Better 5-yr BFFS vs. PORT (84% vs. 77%; p = 0.001)
PIVOTAL trial [17]RCT124All > 30% (roach formula)WPRT vs. PORT–6–9 mo of ADTConfirmed safety of HD-WPRT
Abbreviations: ADT: androgen deprivation therapy, BFFS: biochemical failure-free survival, DFS: disease-free survival, EFS: event-free survival, GETUG: French Genitourinary Study Group, GS: Gleason score, HD-WPRT: high-dose whole pelvic radiotherapy, LNI: lymph node involvement, MO: months, OS: overall survival, PIVOTAL: Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer, POP-RT: Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer, PFS: progression-free survival, PORT: prostate-only radiotherapy, PSA: prostate-specific antigen, RCT: randomized controlled trial, RTOG: Radiation Therapy Oncology Group, WPRT: whole pelvic radiotherapy, yr: year.
Table 3. Overview of selected studies on treating localized prostate disease with node positive N + M0 disease:
Table 3. Overview of selected studies on treating localized prostate disease with node positive N + M0 disease:
Study DesignNo. of N1M0 ptsTreatment GroupsOutcome
ADT as adjuvant treatment Schröder et al. (2009) [23]RCT: EORCT 308846234Immediate ADT vs. delayed ADT NS difference—HR 1.22—CI (0.92–1.62) for prostate CSS
Messing et al. (2006) [24]RCT: ECOG 388698Immediate ADT vs. delayed ADTFavors immediate ADT—better OS—HR 1.84 p = 0.04
EBRT as adjuvant treatmentPilepich et al. (2005) [25]RCT: phase III 85-31263EBRT +ADT vs. EBRT aloneFavors EBRT + ADT, especially high GS (p = 0.002)
Tward et al. (2013) [26]SEER data observational1100EBRT vs. NO EBRT Favors EBRT—
10 yr CSS HR 0.66 p ≤ 0.01
10 yr OS—HR 0.70 p ≤ 0.01
Tiliki et al. (2015) [27]Retrospective, multi-institution1491Adjuvant vs. early salvage therapyFavors adjuvant EBRT in case of pN1—HR 0.66 (p = 0.04)
Fonteyne et al. (2022) [28]RCT, PROPER trial69PORT (arm A) vs. WPRT (arm B)No difference WPRT over PORT; 3 yr. bRES 79% (PORT)% vs. 92% (WPRT), p = 0.08; 3 yr OS 92% (PORT)% vs. 93% (WPRT), p = 0.61
ADT ± any local therapyDa Pozzo et al. (2009) [29]Retrospective, single institutions250ADT vs. EBRT +ADT No difference, 10 yr BCR–free survival 51% (combination) vs. 42% (ADT) p = 0.11–10 yr CSS 70% (combination) vs. 72% (ADT) p = 0.22
Briganti et al. (2011) [30]Retrospective, two institutions364ADT vs. EBRT +ADTFavors adjuvant EBRT —10 yr. CSS 86% (combination) vs. 70% (ADT) p = 0.004; 10 yr OS–74% (combination) vs. 55% (ADT) p < 0.001
Kaplan et al. (2013) [31]SEER data observational577ADT vs. EBRT +ADTNo benefit of adjuvant EBRT: OM 5.35 (EBRT) vs. 3.77 (no EBRT) events per 100 person/yr. (p = 0.193)—PCSM 2.39 (EBRT) vs. 1.3 (no EBRT) (p = 0.354)
Abdollah et al. (2014) [32]Retrospective, two institutions1107ADT vs. EBRT +ADTFavors ADT + adj. EBRT–8 yr. OM-free survival of 88% (ADT + EBRT) vs. 75% (ADT) (p < 0.01)—8 yr. CSM-free 86% (ADT = EBRT) vs. 92% (ADT) (p = 0.08)
Rusthoven et al. (2014) [33]SEER data observational2991RT, RP, or both vs. no local therapyFavors EBRT-10 yr. OS 45% vs. 29, p < 0.001 -10 yr PCSS 76% vs. 53%, p < 0.001
Lin et al. (2015) [34]Observational3540ADT vs. ADT +EBRT Favors ADT + EBRT 50% reduction in ACM–HR 0.50 (p < 0.001
Jegadeesh et al. (2016) [35]Retrospective826ADT vs. ADT + EBRTFavors ADT + EBRT–improved OS—HR 0.67 (p < 0.001)
Van hemelryk et al. (2016) [36]Retrospective–case matched69Case matching of pN1 and pN0 after EBRT +ADT5 yr bRFS 65% vs. 79% (p = 0.08). 5 yr cRFS 70% vs. 83% (p = 0.04). 5 yr PCSS 92% vs. 93% (p = 0.66). 5 yr OS 82% vs. 80% (p = 0.58)
Poelaert et al. (2016) [37]Retrospective154ADT + WPRT 5 yr CSS 96%. 5 yr bRFS 67%.5 yr cRFS 71%-5 yr OS 89%
Seisen et al. (2018) [38]Observational1987ADT vs. ADT + local therapyFavors ADT + local therapy
Bryant et al. (2018) [39]Observational648ADT vs. ADT + EBRTFavors ADT + EBRT.PCSS HR 0.05 p = 0.02.ACM HR 0.38 p < 0.001
Toujer et al. (2018) [40]Retrospective1338Observation vs. ADT alone vs. ADT + EBRT Favors ADT + EBRT over ADT alone, HR 0.46 for OS (p < 0.0001); Favors ADT + EBRT over observation, HR 0.41 for OS (p < 0.0001)
Gupta et al. (2019) [41]Retrospective, 3 institutions8074Observation vs. ADT alone vs. ADT + EBRTFavors ADT + EBRT over ADT alone, HR 0.76 for OS (p = 0.007)—Favors ADT + EBRT over observation, HR 0.77 for OS (p = 0.008)
ADT ± systemic treatment Vale et al. (2016) [42]Systematic review, GETUG-12, RTOG 0521, STAMPEDE945ADT ± Docetaxel OS, no benefit of adding Docetaxel, HR 0.87, (p = 0.218)
Ahlgren et al. (2018) [43]RCT, SPCG-12 trial55/459–(27 arm A and 28 arm B)Arm A: Docetaxel.
Arm B: Surveillance 		No difference in time to BCR > 0.05 ng/mL (p = 0.06)
Attard et al. (2022) [44]RCT 1: Abiraterone trial; RCT 2: Abiraterone + enzalutamide trial
STAMPEDE protocol		7741: ADT vs. ADT + abiraterone
2: ADT vs. ADT + abiraterone + enzalutamide 		Favors ADT + abiraterone (combination) vs. ADT (alone).6 yr metastasis-free survival 82 vs. 69% HR 0.53 p < 0.0001
N1M0 patients: patients with node-positive disease either pathologically or clinically; ADT: androgen deprivation therapy; bRFS: biochemical relapse-free survival; CI: confidence interval; cRFS: clinical relapse-free survival; CSS: cancer-specific survival; EBRT: external beam radiotherapy; GS: Gleason score; HR: hazard ratio; NS: non-significant trial; OS: overall survival; OM-free: overall mortality free; PORT: Prostate-Only Radiotherapy; PCSM: prostate cancer-specific mortality; RCT: randomized controlled; RP: radical prostatectomy; RT: radiotherapy; BCR: biochemical recurrence; SEER: Surveillance, Epidemiology, and End Results; WPR: whole pelvic radiotherapy; yr: year; CSM: cancer-specific mortality, STAMPEDE: Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy; GETUG: French Genitourinary Study Group; RTOG: Radiation Therapy Oncology Group; PCSS: prostate cancer-specific survival; ECOG: Eastern Clinical Oncology Group; EORCT: European Organization for. Research and Treatment of Cancer
Table 4. Selected trials of metastasis directed therapy (MDT) in oligorecurrent prostate cancer.
Table 4. Selected trials of metastasis directed therapy (MDT) in oligorecurrent prostate cancer.
Study (Ref)NImaging/ N◦ of Mets% of Nodal LesionsMDT/DesignMedian FUOutcome
Harrows SABR-COMT phase II RCT [58]16/99Conv./1–5 PSOC vs. SBRT + PSOC5.7 yr8 yr OS: HR 0.05; 8 yr PFS: HR 0.45
OST [59]-STOMP-phase II RCT62PET-CHO/1–355%Surveillance vs. SBRT3 yrADTF: 13 vs. 21 mo (HR 0.06), p = 0.11)
Phillips- [57] ORIOLE–phase II RCT4Conv. PSMA-PET 1–358%Surveillance vs. SBRT19 moPFS: 81% vs. 39% (p = 0.005) HR 0.03 (p = 0.002)
Siva–[60] POPSTAR phase I33CT, BS, F-PET/1–339%SBRT (ADT in 33%)24 mo2 yr Local-PFS 93%/2 yr DFS 39%/2 yr ADTF 48%
Glicksman [61] PSMA MRgRT phase II74PSMA-PET, MR/ 237%SBRT (87%) or surgery (no ADT)41 moPSA response: Median 21 mo /PSA-PFS median 45 mo
Holscher [62]
OLIP phase II		63PSMA-PET, MR/ 1 lesion68%SBRT 77% CRT 50 Gy 23%—No ADT37 moNo Grade > 2 treatment related toxicity time to ADT 20.6 mo
Conde Moreno [63]
SBRT-SG05 phase II		67PET-CHO, MR/‘1–557%SBRT + ADT41 moMedian DPFS 54.2 mo
N: number of patients; N◦ MET: number of metastasis allowed; MDT: metastasis-directed therapy; Conv: conventional; PET-CHO: positron emission tomography-choline; CT: computerized tomography; BS: bone scan; MR: magnetic resonance; MDT: metastasis-directed therapy; SOC: standard of care; SABR: stereotactic ablative radiation therapy; SBRT: stereotactic body radiation therapy; ADT: androgen deprivation therapy; CRT: conventional radiation therapy; yr: years; mo: months; P: primary; S: secondary; PFS: progression-free survival; ADTF: freedom from ADT; DPFS: disease progression-free survival; HR: hazard ratio; PSMA: prostate-specific antigen membrane; PSMA-PET: prostate-specific antigen membrane-positron emission tomography; RCT: randomized controlled trial; mo: months; yr: years; MRgRT: magnetic resonance-guided radiation therapy; SABR-COMT: stereotactic radiation for the comprehensive treatment of oligometastases; STOMP: Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence; ORIOLE: Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr; POPSTAR: Patients with Oligometastases from Prostate Cancer Treated with Stereotactic Ablative Radiotherapy; OS: overall survival; PSA: prostate specific antigen.
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Shaheen, H.; Roach, M., 3rd; Elsemary, E.E. SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer. Soc. Int. Urol. J. 2025, 6, 46. https://doi.org/10.3390/siuj6030046

AMA Style

Shaheen H, Roach M 3rd, Elsemary EE. SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer. Société Internationale d’Urologie Journal. 2025; 6(3):46. https://doi.org/10.3390/siuj6030046

Chicago/Turabian Style

Shaheen, Haitham, Mack Roach, 3rd, and Eman Essam Elsemary. 2025. "SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer" Société Internationale d’Urologie Journal 6, no. 3: 46. https://doi.org/10.3390/siuj6030046

APA Style

Shaheen, H., Roach, M., 3rd, & Elsemary, E. E. (2025). SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer. Société Internationale d’Urologie Journal, 6(3), 46. https://doi.org/10.3390/siuj6030046

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