【2022 ESMO】Keeping up with the Times│ Discussion on the Management of Oligometastatic Hormone-Sensitive Prostate Cancer

*For medical professionals only

Held online and offline in Paris, France from September 9-13, 2022 to September 2022, the European Society for Internal Oncology (ESMO) is the most prestigious and influential oncology conference in Europe, with more than 30,000 professionals participating each year to share and discuss the latest hot spots and advances in the field of oncology, and to translate science into the best strategies to bring more hope
to patients.

This paper mainly presents
this hot topic based on the "management of oligometastatic prostate cancer" by four professors including Nicholas D.
James in the conference.

Definition of oligometastatic hormone-sensitive prostate cancer

Olignometastatic hormone sensitive prostate cancer (omHSPC) is in the "middle" stage of clinical limitation and extensive metastasis, and patients with oligometastasis have a better survival prognosis than extensive metastasis
.

In 1995, Hellman et al.
hypothetically proposed that oligometastatic disease might be a more curative type of
disease.

So far, there is still no definite definition of omHSPC, but most studies have used the ≤ 5 metastases as their definitions
.

In other studies, such as CHAARTED ^[1], 4 sites of high and low tumors (high tumors defined as visceral metastases, or bone metastases≥ were used, at least 1 of which is outside the spine or pelvis; If the high tumor load is not satisfied, it is considered to be a low tumor) to stratify
the patient.

In most cases, patients with oligometastases and low tumors are highly overlapping
.

Clinical assessment of the degree of disease progression in patients with metastatic prostate cancer usually relies on traditional imaging tools, and in recent years, the new imaging technology PSMA PET/CT has significantly outperformed traditional imaging
in terms of specificity and sensitivity.

Although the detection accuracy of new imaging techniques has been improved, the impact on treatment options and patient benefits needs to be confirmed
by more clinical study data.

The 2022 European Association of Urology (EAU) guidelines strongly recommend that when using PSMA PET/CT to increase detection sensitivity, it is also important to take into account that changes in subsequent treatment regimens still lack evidence to guide them
.

At present, the omHSPC type is divided into: newly diagnosed oligometastatic hormone-sensitive prostate cancer (simultaneous oligometastasis) and oligorecurrent prostate cancer after radical therapy (heterochronic oligometastasis
).

omHSPC requires a personalized comprehensive treatment model, and it is important to distinguish between simultaneous and heterotemporous omHSPC as this affects the patient's prognosis
.

The survival benefit of patients with heterochromia oligometastasis is significantly better than that of patients with simultaneous oligometastasis
.

Treatment options for oligometastatic hormone-sensitive prostate cancer

Treatment options for patients with omHSPC are prolonged overall survival and improved quality of life (QoL), and treatment options include primary surgery and radiation therapy based on androgen deprivation therapy (ADT), intensive systemic therapy (ADT+Abitron/Apatamide/Enzalumine), and metastatic therapy (ADT+MDT).

Radiation therapy with ADT in combination with primary focus improves survival benefit in patients with omHSPC compared with ADT alone
.

Subgroup analysis of 432 mHSPC patients in the HORRAD ^[2] trial found that the risk ratios of <5 metastases ≥ 5 and 5 were 0.
68 and 1.
06, respectively, so the researchers could not rule out the survival benefit<b13> of radiotherapy in patients with low tumors (< 5 metastases).
<b14>Subgroup analysis of the STAMPEDE ^[3] study showed that ADT in combination with primary focal radiotherapy compared with ADT improved overall survival (OS) and fail-safe survival in newly diagnosed patients with low tumor load mHSPC
.

Meta-analyses of the two studies showed that primary radiotherapy improved 3-year survival in patients with newly diagnosed omHSPC (5 metastatic <) by approximately 7% <b18>[4
].

ADT-based plus metastatic targeted therapy (MDT) may be an effective way to treat omHSPC
.

Stereotactic ablation radiotherapy (SABR) is one of the most promising means
.

The ORIOLE[5] and STOMP[⁶] studies were two randomized, phase II.
clinical trials in which the results of the STOMP and ORIOLE studies were pooled and found that MDT prolonged median progression-free survival (PFS) compared with the observation group in patients with heterochrophic omHSPC [co-risk ratio (HR), 0.
44; 95% CI, 0.
29 to 0.
66; P<001<b14>], The long-term results of these only two randomized controlled trials conducted in heterotemporal omHSPC suggest a sustained clinical benefit
of MDT over observation.

Figure 1 Summary analysis of STOMP and ORIOLE research results

Systematic therapy is the cornerstone of their comprehensive treatment model for patients with omHSPC
.

The 2022 EAU guidelines recommend ADT-based combination therapy as the standard of care (SOC)
for mHSPC patients.

In the treatment of patients with mHSPC with low tumor burden, ADT in combination with new endocrine therapies such as apatamide, abiraterone, or enzalumine all showed better survival benefits
than ADT alone.

Although the PEACE-1[⁷] and ARASENS^[8] studies suggest that the triple regimen has a better survival benefit than the dual regimen of ADT combined chemotherapy, speaker Professor Silke Gillessen argues that for patients with omHSPC, she prefers to choose new endocrine drugs instead of chemotherapy; Because the PEACE-1 and ARASENS studies included a small number of patients with low tumors or oligometastases, the conclusions were insufficient to support clinical treatment options
.

Expert reviews

Ostrogenic disease is not a new concept, but it is a "new" clinical state, and clinicians are increasingly enthusiastic about its treatment
.

The definition of oligometastasis is not completely unified at present, and the core issues involved include the time to find the metastatic lesion, the diagnostic method, the location and number of metastatic lesions, etc
.

mHSPC patients can also be divided into high tumors and low tumors according to tumor burden, while patients with low tumors and oligometastases are highly overlapping
.

At present, the diagnosis of oligometastasis is still based on traditional imaging, and there is no clear conclusion
on the application of new generation imaging methods such as PSMA PET/CT in diagnosis.

Earlier/more distant metastases can be detected with higher sensitivity and specificity, and whether this will alter treatment options and clinical outcomes for patients remains to be further discussed
.

At present, there are not many centers for PSMA in China, and the scope of application is not particularly wide, so domestic experts should further agree
on which patients need to use PSMA examination.

In the clinic, ADT combined with local radiotherapy or surgery is also a treatment modality
that is often taken into account.

The previously mentioned HORRAD and STAMPEDE studies have demonstrated that ADT combined with local radiotherapy can provide survival benefits for patients with low tumor load mHSPC
.

In clinical practice in China, surgery is a more common local treatment, and the results of a prospective, open-ended, randomized, controlled Phase II clinical study led by Professor Ye Dingwei in 2016 suggest that ADT combined surgery can be used by experienced physicians to treat patients with omHSPC ^[9].


We also expect more mature data to be published in the study, and in clinical practice, we also expect that such treatment attempts will bring tangible clinical benefits
to patients.

ADT combined with the new endocrine therapy represented by apatamide has significant survival benefits for patients with low tumor load mHSPC, so if such a treatment is combined with local surgery or radiotherapy, will it further improve the patient's benefit and achieve the clinical effect of 1+1+1>3? A number of clinical studies are currently underway, and we look forward to the early release
of data.

In addition, for patients with omHSPC, a triple treatment based on ADT combined chemotherapy may need to be used with
caution.

The benefit of ADT+ topical therapy + metastatic targeted therapy in patients with omHSPC is currently poorly available, but in clinical practice targeted therapy for specific patients, such as significant local pain or weight-bearing bone metastases, targeted metabolic therapy
may be attempted.

The management of omHSPC patients is a hot issue, and some of the above issues have also been discussed and voted on at the APCCC [^{10] 2021}: 77% of experts believe that PSMA PET/CT should be used in high-risk limited patients for staging, while there is no uniform recommendation on whether to use PSMA PET/CT in patients with oligometastatic HSPC; In patients with simultaneous omHSPC diagnosed with second-generation imaging (NGI), 61% of experts will use systematic therapy + local treatment of the primary focus + MDT; Of the choice of systematic treatment options, 89% of specialists will use ADT in combination with new endocrine therapy
.

In summary, there are many decisions in the management of oligometastatic therapy that require individual choices by clinicians; We also expect that in the era of systematic treatment based on new endocrine drugs, local therapy with or without topical therapy and metastatic targeted therapy can be released more quickly and relevant data and expert consensus can emerge
.

Professor Hou Sichuan

Chief Physician, Professor, Doctoral Supervisor of Qingdao Municipal Hospital

Doctor of Clinical Medicine, Peking University Health Sciences

Assistant Dean of the Third Clinical Medical College of Qingdao University

Assistant to the president of Qingdao Municipal Hospital, director of the Department of Surgery

Director of the Surgical Base of Qingdao Municipal Hospital Residential Training Base, Director of the Urology Center

He is the leader of the clinical key specialty urology department in Shandong Province

Qingdao key discipline outstanding discipline leader

He is the chairman of the Urology Committee of Shandong Association of Integrative Traditional Chinese and Western Medicine

Vice Chairman of Urology Branch of Shandong Medical Association

Vice Chairman of Shandong Andrology Society

Vice Chairman of Shandong Medical Doctor Association

Member of the Chinese Society of Sexuality

Director of Shandong Sex Society

The first most beautiful doctor in Qingdao

He has won honorary titles such as Shandong Fumin Xinglu Medal and Shandong Provincial Health Guard

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