Publikacje dot. OPC (Oligometastatic Prostate Cancer)

Publikacje dot. OPC (Oligometastatic Prostate Cancer)

Nieprzeczytany postautor: zosia bluszcz » 09 wrz 2017, 05:04

ASCO 2016
Education Session on Friday, June 3

Treating Oligometastatic Disease in Prostate Cancer

June 7, 2016
Few guidelines exist for treating oligometastatic prostate cancer (OPC), with little consensus even on the criteria that define the disease.
Yet consideration of clinical trial data and anecdotal patient information can help oncologists weigh available treatment options, including the potential use of ablative techniques like surgery and stereotactic ablative radiation therapy, to either help delay disease progression or avoid hormone therapy for patients with OPC, according to speakers at an Education Session on Friday, June 3.

Biologic theories of prostate cancer metastases have evolved but presently a multidisciplinary perspective suggests OPC involves a limited number of metastases that develop early from monoclonal expansion that can seed other sites over time, said Session Chair Neha Vapiwala, MD, of the University of Pennsylvania. “This offers both an attractive target and a potential window of time.”

The session, “Oligometastatic Disease in Prostate Cancer: Treating the Patient or the Scan?,” featured discussions of the definition of OPC and effective management strategies, if and when surgery may be a useful treatment, and if radiation therapy has a role in ablation therapy for OPC.

Dr. Christopher Sweeney

A Metastatic, Hormone-Sensitive State
“There is no harmonized definition of OPC, nor good data to quantify its frequency,” said Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute. “It presents either as de novo metastatic disease or as relapsed after local therapy, but there is an increasing appreciation that it should be considered a unique entity.” During prostate cancer disease progression, OPC presents early as a hormone-sensitive state with rising prostate-specific antigen (PSA) levels and low burden of metastatic disease. Dr. Sweeney suggested that approximately 9,000 patients present with de novo metastatic OPC each year in the United States.

Clinical trial groups have different definitions of OPC based on conventional imaging CT and bone scan to define subgroups.
All agree that OPC lacks visceral disease and involves nodal disease.
A general consensus also includes the presence of three or fewer vertebral or pelvic bone metastases.

“In all of the phase III studies, OPC patients with a low tumor burden treated only with androgen deprivation therapy [ADT], have a median overall survival [OS] of about 7 years,” Dr. Sweeney explained.
OS is reduced to approximately 3 years in metastatic prostate cancer with a higher tumor burden.

As new imaging modalities emerge, such as prostate-specific membrane antigen (PSMA)-based PET and gallium scanning, choline PET imaging, whole-body MRI, and sodium fluoride PET, studies will reveal micrometastatic lesions that were invisible to conventional imaging.
Dr. Sweeney explained that the patient with micrometastatic diseases is possibly cured with early androgen inhibition.

A definitive treatment strategy for OPC remains uncertain, ranging from ADT alone to comprehensive therapy with ADT, systemic chemotherapy, and ablative techniques. After presenting several case studies, Dr. Sweeney suggested that “we can do better than just ADT alone” by adding radiation therapy to ADT.
He concluded by offering his preference to use ablative local therapy to all disease plus ADT for 2 years, stopping if PSA levels are higher than 0.2, and then assessing degree of control.

Surgery Appropriate for Low-Volume Nodal Disease

Traditional thought has been that radical prostatectomy (RP) is historically reserved for low-stage/low-risk disease, explained R. Jeffrey Karnes, MD, of Mayo Clinic. But does it benefit men with metastatic disease? “Metastasis can lead to further metastasis and does not always have to come from the primary,” he said of the importance of treating both the primary tumor and the metastasis.

Dr. R. Jeffrey Karnes

Referencing several studies, Dr. Karnes showed that RP in addition to hormone therapy improves OS at 10 years to 65%, compared with 30% for hormone therapy alone.
“This is fairly suggestive, favoring treating the primary even in the face of positive pelvic nodes, which are usually occult micrometastatic nodes,” he said.
Another study showed that surgery can cure low-volume metastasis with favorable characteristics such as a Gleason score (GS) of 7, negative margins, and two or fewer positive nodes.

Approximately one-third of patients who have already undergone RP will have a biochemical recurrence.
For these patients, salvage lymph node dissection (sLND) has been shown to delay further progression/recurrence and postpone hormone therapy. “
This is what drives our men to seek other therapies,” says Dr. Karnes. “They want to avoid hormone therapy, usually at all costs.” Optimal candidates for sLND are those with PSA lower than 4, pelvic lesion(s), GS of 7 and T2 on RP, and non–castration-resistant prostate cancer.

“Patients are looking to us for alternatives to hormone therapy,” said Dr. Karnes. “Surgery in the local metastatic prostate cancer state does make sense, especially for nodal disease, often as a part of a multimodal therapy package.”

Radiation Therapy for Metastatic Prostate Lesions

Similar to Dr. Karnes’ recommendation for surgery in some patients with OPC, Dr. Vapiwala outlined suggestions for appropriate local radiation therapy (RT) of metastatic lesions in this population.

She noted that stereotactic ablative radiotherapy (SABR or SBRT) offers multiple advantages over standard conventional radiotherapy (1.8 to 2.0 Gy/day).
She presented findings showing that high-dose SABR (over 21 Gy as a single dose or over 8 Gy per fraction) provide approximately 90% control of the local radiated metastatic site.

“We have come a long way in our techniques and capabilities in radiation therapy,” said Dr. Vapiwala. High precision and conformity to target are critical given the extreme dose gradient between the target lesion and organs at risk
She credits the availability of advanced imaging technologies, such as MRI for the spinal cord and choline-PET/CT for nodal metastases that provide real-time, image-guidance capabilities, together with precise stereotactic SABR tools, and improved immobilization techniques, for improving the safety and efficacy of SABR in the OPC population.

Dr. Vapiwala suggested radiation therapy may be an appropriate strategy for OPC in the presence of limited quantities and locations of metastases, after a largely effective systemic treatment to eradicate residual deposits, or with one or more distant metastases in one or more organs that are amenable to local treatment.

She cited better prostate cancer–specific survival in patients who received primary curative treatment who have a longer time from primary treatment to presentation of OPC. Other positive criteria are node or axial skeletal involvement and a lower number of metastases (recurrent disease with five or fewer metastases in bone, especially the spine.) “Perhaps this is the population in whom we should focus our efforts,” she said.

However, unlike in oligometastatic colorectal and lung cancers, the current guidelines for OPC do not include ablative radiation therapy, which is limited to a purely palliative role at best. “However, I believe there will hopefully be techniques that will allow us to identify subsets of these patients with oligometastatic disease that are appropriate for high-dose ablative radiation therapy in a way that can alter prognosis, not just palliate symptoms,” said Dr. Vapiwali. She cited studies supporting the idea that RT may be used to delay progression as well as to delay the onset of ADT.

To date, approximately 140 ongoing clinical trials are exploring the role of ablative RT in different locations.
Of those, 53 are focused on oligometastatic disease. As the results from these and other prospective trials become available, Dr. Vapiwali believes the role of ablative local RT will become clearer. Until then, the most popular dose range for most of the completed SABR studies is one 20-Gy treatment or three 10-Gy doses.

“We know that ADT delays clinical progression and can prolong survival in asymptomatic patients with prostate cancer,”
said Dr. Vapiwali. “And we know radiation is an excellent collaborator and works well with ADT.”
But the question remains: How can radiation therapy be better incorporated?

—Alice McCarthy ... ate-cancer


Oligometastatic Prostate Cancer
Daniel J. Stevens, BSc(Hons), MBBCh(Hons), MRCS Prasanna Sooriakumaran, BMedSci(Hons), BMBS(Hons), MRCS, PhD, PGCMedLaw, ECFMG, ADCClinInv, FRCSUrol, FEBU* Address * Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Room 6607, Level 6, Headington, Oxford, OX3 9DU, UK Email:
Published online: 27 October 2016

Opinion statement
The mainstay of treatment for men with three or fewer non-castrate metastatic lesions outside of the prostate remains morbid palliative androgen deprivation therapy. We believe there is now a significant body of retrospective literature to suggest a survival benefit if these men have radical treatment to their primary tumour alongside ‘metastasisdirected therapy’ to the metastatic deposits. However, this regimen should be reserved to high-volume centres with quality assurance programmes and excellent outcomes. Patients should be made clear as to the uncertainty of benefit for this multi-site treatment strategy, and we await the publication of randomised controlled trials reporting in the next 5 years.

Oligometastatic disease can be defined as the development of three or fewer non-castrate lesions outside of the primary tumour [4••]. These can be bone metastases or in the soft tissue.
The concept of oligometastatic disease for all cancers is based around a stepwise progression whereby a cancer initially metastasises in a limited way, before acquiring widespread metastatic behaviour [5].

In a range of solid tumours [6–8], it is hypothesised that this intermediate step represents a different biology compared to extensive metastatic disease, and therefore, it represents an opportunity to influence the rate of progression, and possibly even cure the patient. It is thought that in oligometastatic states, the true metastatic growth potential is limited. This may be secondary to tumour microenvironments in the primary lesion remaining sufficiently hospitable that evolutionary clonal pressure is low; therefore, cancer cells that slough off the primary do not have the properties necessary to survive the circulation and invade target organ sites effectively [9•].
This is contrasted with systemic metastatic disease where the primary tumour has created many undifferentiated aggressive clones that actively migrate out of the primary tumour and have the characteristics to survive and invade target organ sites.
The clinical implication of oligometastatic disease is that treatment of metastases alongside the primary tumour (if not already treated) could result in long-term survival or cure [10, 11]. Treatment of oligometastatic disease may also decrease disease-related morbidity and reduce overall tumour burden.
However, without randomised controlled trials, it is very difficult to know if the treatment of oligometastatic disease helps the patient. The current literature in all cancer types is limited by using varying definitions of oligometastasis, with a variety of endpoints and at different levels of evidence [9•].
With regard to prostate cancer, while standard treatment remains long-term palliative androgen deprivation treatment, there is emerging data that treatment of the primary with stereotactic body radiotherapy (SBRT) or even radical prostatectomy may impact survival, slow symptomatic disease progression, and reduce the need for palliative surgical intervention [12–15]. In this review, we evaluate the three main treatment approaches for oligometastatic prostate cancer—systemic therapy, treatment of the primary tumour and metastasis-directed therapy.

Oligometastatic Prostate Cancer.pdf
(291.6 KiB) Pobrany 11 razy


Oligometastatic prostate cancer: Metastases- directed therapy?

Hein Van Poppel *, Gert De Meerleer, Steven Joniau Department of Urology and Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
Available online 20 July 2016

Since the introduction of anatomical and functional imaging with multiparametric magnetic resonance imaging and choline or prostate-specific mem- brane antigen positron emission tomography–computed tomography, we are able to diagnose a previously unknown disease, the oligometastatic prostate cancer after local therapy. Reports on surgical and radiation treatment for low- volume metastatic recurrence have shown promising results, with definitive cure in few but a relevant delay of androgen-deprivation therapy with both treatment methods.
Obviously, these results need to be validated with prospective randomised data.

Metastatic prostate cancer is classically treated with hormonal manipulation. Oligometastatic prostate cancer is a relatively new concept. It was originally defined as five or less metastatic sites [1]. It was proposed as a clinically significant state separate from the poly- metastatic disease [2] and considered to be less aggressive than other metastatic phenotypes [3]. Importantly, oligometastatic prostate cancer was shown to have a
different microRNA profile than polymetastatic disease [4]. Obviously, patients with oligometastatic disease are prone to progress at the initial metastatic foci. The rationale of metastasis-directed treatment comes from the concept that it might delay or avoid the castrate- resistant prostate cancer status by eradicating castration-resistant clones. Indeed, metastasis-directed treatment might postpone the initiation of androgen- deprivation therapy (ADT) and hypothetically may lead to improved survival [5].

Salvage LND
For most patients with oligometastatic involvement of the pelvic nodes, a salvage LND will allow postponement of ADT and has limited toxicity.
About 50% will achieve a complete PSA response and about one-third will remain free of PSA relapse for 5 years.
However, these data need to be validated in prospective randomised trials, whilst the impact on the results of concomitant ADT needs to be analysed further.

Salvage RT
Salvage RT to bone or lymph nodes allows postponement of ADT and is also not very toxic.
However, salvage RT will not achieve undetectable PSA levels unless associated with ADT.
It is not known yet how many patients will be free of PSA at 5 years.
The only data available today are on CPFS at 3 years, which also need to be validated with prospective randomised data.

In conclusion, metastasis-directed therapy is promising but needs validation in a randomised controlled trial.
For the time being, all we can do is optimise selection and individualise the treatment strategies.


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