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Prostatic Neoplasms

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Genital Neoplasms, Male

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Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Disease Attributes

Salvage lymphnode dissection is performed on the PSMA PET positive side, according to template (obturator, iliac external, iliac internal, iliac commun) and possibly including other anatomical pelvic regions

In addition, a salvage lymphnode dissection is performed on the opposite side with resection of the corresponding fields, which were taken on the PSMA-PET positive side

A salvage lymphnode dissection is performed in all study patients (both arms)using standard surgical techniques (openly or DaVinci).In patients who were randomized to the bilateral pelvic lymphnode dissection group, a salvage lymphadenectomy was also performed on the opposite side with resection of the corresponding fields that were removed on the PSMA-PET positive side (th "Blinding" must be guaranteed during pathological assessment)

Salvage Lymphnode dissection

Tobias Maurer, PD Dr.

Markus Graefen, Professor

Anke Renter

Significant advances in molecular nuclear medicine imaging in prostate cancer have been achieved in recent years. In particular, the introduction of prostate-specific membrane antigen (PSMA) -based tracers has significantly influenced diagnostic imaging of prostate. If cancer recurs after surgical removal of the prostate, targeted PSMA PET (positron emission tomography) can detect metastases even at very low PSA (prostate-specific Antigen) values. This increasingly allows individualized specific therapy of patients with prostate cancer recurrence. PSMA PET has now been included in national and international guidelines for the diagnosis of patients with biochemical recurrence of prostate cancer.

Especially in patients in good general condition, with potentially longer life expectancy and early localized PSA recurrence, advances in molecular imaging are increasingly turning local therapy concepts into focus. Here both, radiotherapeutic (salvage radiotherapy of the lymphatic drainage) and surgical interventions (salvage lymph node dissection = removal of the pelvic lymph nodes) are offered on an individual basis.

These regional therapies mainly aim to achieve a delay of further progression of the prostate cancer disease, and thus delay the initiation of palliative, sustained drug therapy. Previous standard or common practice at salvage lymph node dissection is the removal on both sides of the pelvic lymph nodes even if only one-sided suspicious lymph nodes are detected on imaging. Although the complications of salvage lymph node dissection are usually minor and manageable, they can still lead to impaired lymphatic drainage, leg edema, lymphocele formation or other surgical complications.

The aim of the present study is to investigate whether a unilateral pelvic lymph node dissection on the side of conspicuous PSMA PET is sufficient and a dissection on the contralateral side can be dispensed without negatively impacting oncological outcomes and thereby sparing the patient the potential additional complications of a bilateral pelvic lymph node dissection.

In this prospective randomized study, patients with early biochemical recurrence after radical prostatectomy and with PSMA-PET positive unilateral pelvic metastatic lesions are assessed as to whether unilateral and bilateral salvage lymph node dissection are oncologically equivalent. For this, the following endpoints will be evaluated:

* complete biochemical response (cBR: PSA \<0.2ng /ml) after salvage lymph node dissection
* biochemical freedom from recurrence without further prostate-cancer-specific therapy (time from salvage lymph node dissection to first PSA value\> 0.2ng / ml)
* prostate cancer-specific therapy-free time (time from salvage lymph node dissection to initiation of prostate cancer specific therapy) In addition, the diagnostic accuracy of the preoperative PSMA PET, which led to the indication of salvage lymph node dissection, is to be investigated in the context of the study and the standardized one- or two-sided template lymph node dissection. Furthermore, it should be investigated whether there is a reduction of surgery-associated side effects in patients undergoing unilateral salvage lymph node dissection. In addition, quality of life and psychological stress of patients is systematically recorded by means of validated questionnaires. Since salvage lymph node dissection may also be carried out with the help of currently experimental preoperative labeling with PSMA ligands for easier intraoperative localization (PSMA radioguided surgery), a comparison of conventional salvage surgery and the PSMA radioguided surgery is also planned. However, if applied to patients, PSMA radioguided surgery is performed outside of the study protocol and is explicitly not part of the study protocol.

In case there is no complete biochemical response (cBR, PSA \<0.2ng / ml) or, after reaching cBR, a further increase in PSA above 0.2ng / ml threshold is observed after salvage lymph node dissection, an attempt should be made to localize recurrence disease using PSMA PET. This should provide indirect information as to whether re-irradiation following salvage lymph node dissection could be a useful approach and should be investigated in future studies. However, PSMA PET is recommended in the study, but is optional and therefore to be performed outside of the study protocol.

Early Prostate Cancer Recurrence With PSMA PET Positive Unilateral Pelvic Lesion(s)

Early Prostate Cancer Recurrence With PSMA PET Positive Unilateral Pelvic Lesion(s): is One-sided Salvage Extended Lymph Node Dissection Enough

cBR: PSA \<0.2ng / ml after salvage lymph node dissection without adjuvant prostate cancer specific therapy

University Hospital Hamburg, Institute of Tumor Biology

Martini-Klinik am UKE GmbH

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy

addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment

whole pelvic radiotherapy

metastasis-directed treatment

salvage Lymph Node Dissection

LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

androgen deprivation therapy

Piet Ost, PhD

A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).

A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of metastases, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.

PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

PEACE V: A Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)

Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by choline, FACBC or PSMA PET-CT or death due to any cause

Clinical Progression-free survival is defined as time between randomization and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause

For patients who had previous RP at initial diagnosis, a biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/ml with a confirmatory rise at least 2 weeks later. For patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA

Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.

Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients

Validated questionnaire assessing the health-related QOL of prostate cancer patients

Cancer specific survival will be read as the time from trial randomization to the date of death due to prostate cancer

Overall survival will be read as the time from trial randomization to the date of death from any cause

Time to hormonal treatment is defined as the time from trial randomization to start of hormonal treatment

Time to castration resistant disease is defined as the time from trial randomization until castration resistant status

Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D-5L)

University Hospital, Geneva

University Ghent

Patients will undergo extended pelvic salvage lymph node dissection

Open pelvic surgery to dissect pelvic lymph nodes. The landmarks for dissection are: 1. Inferior mesenteric artery 2. Ilioinguinal nerve 3. Inguinal ligament 4. Dorsal pelvic floor 5. Urinary bladder

Salvage lymph node dissection

Shahrokh Francois Shariat, MD

Despite continuous technical improvements in urologic surgery, up to 40% of prostate cancer patients will develop biochemical recurrence after radical prostatectomy (RP), potentially because of micro metastasis at the time of the primary surgery.

With improved radiological modalities and nuclear medicine tracers like 68Ga-PSMA PET/CT, which allow the localization of the site of recurrence, there is increasing interest in metastasis directed therapies, such as salvage lymph node dissection.

The pelvic extended salvage lymph node dissection (sLND) is a promising option for treating prostate cancer patients with local recurrence after radical prostatectomy with curative intent. Several retrospective series has been published to determine the local value of sLND. Despite the first data seem to be feasible and promising, to date no prospective evaluation has been made. Thus sLND is still experimental according to the guidelines and is considered as an off label therapy.

This prospective single center phase I/II study was conducted to investigate the safety and early efficacy of salvage lymph node dissection in prostate cancer patients with local pelvic recurrence after radical prostatectomy (RP) with curative intention.

Salvage Lymph Node Dissection in Prostate Cancer Patients With Recurrence After Radical Prostatectomy

Safety and Efficacy of Salvage Lymph Node Dissection in Prostate Cancer Patients With Nodal Recurrence After Radical Prostatectomy With Curative Intent - a Prospective Single Center Phase I/II Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early Prostate Cancer Recurrence With PSMA PET Positive Unilateral Pelvic Lesion(s)	NCT04271579	Prostate Cancer	Salvage Lymphno...	18 Years - 75 Years	Martini-Klinik am UKE GmbH
PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases	NCT03569241	Prostate Cancer Prostate Cancer... Metastatic Canc... Oligometastatic...	whole pelvic ra... metastasis-dire... salvage Lymph N... androgen depriv...	18 Years -	University Hospital, Ghent
PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases	NCT03569241	Prostate Cancer Prostate Cancer... Metastatic Canc... Oligometastatic...	whole pelvic ra... metastasis-dire... salvage Lymph N... androgen depriv...	18 Years -	University Hospital, Ghent
Salvage Lymph Node Dissection in Prostate Cancer Patients With Recurrence After Radical Prostatectomy	NCT02974075	Prostate Cancer...	Salvage lymph n...	18 Years - 75 Years	Medical University of Vienna

Spots Global Cancer Trial Database for salvage lymph node dissection