【2022 ESMO】Excellence Patients with PSA≤0.2ng/ml after novel endocrine therapy mHSPC have a more significant survival benefit

*For medical professionals only

The 2022 European Society for Internal Oncology (ESMO) Annual Meeting was held
in Paris from September 9 to 13 local time.

At this ESMO conference, many new data in the field of oncology were announced, including a number of heavy research results
in the field of urological tumors.

This paper mainly shares two research advances related to the effect of PSA levels and intensive therapy on the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC) in the field of prostate cancer, and invites Professor Luo Guangheng from Guizhou Provincial People's Hospital to conduct in-depth interpretation
.

PEACE-1 Study:

PSA levels at 8 months have a significant effect on prognosis in patients with ^mHSPC[1].

PEACE-1 studies have demonstrated that combined with abirtrolone on the basis of ADT or ADT+ docetaxel can significantly extend the overall survival (OS)
of mHSPC patients.

This study analyzed the correlation between PSA levels at 8 months in mHSPC patients in the PEACE-1 study and radiographically progression-free survival (rPFS) and OS (PSA group cutoff values were 0.
2 ng/ml and 4 ng/ml).


The median follow-up was 4.
4 years
.

The results showed (Figure 1) that no matter what treatment was taken, rPFS was significantly prolonged compared with OS in mHSPC patients with PSA >< 0.
2 ng/ml compared with OS, and rPFS was significantly prolonged compared with OS at 8 months, and rPFS was 3.
7 years in ADT+ docetaxel group, 4.
7 years in ADT+ docetam + abiraterone group, and OS was not achieved; PSA < mHSPC patients with 4 ng/ml regardless of treatment.
rPFS was also significantly longer than PSA >4 ng/ml compared to OS; In addition, mHSPC patients with 8-month PSA < 0.
2 ng/ml also benefited more significantly
from rPFS and OS than PSA< 4 ng/ml.

Figure 1 rPFS versus OS in patients with different PSA levels at mHSPC at 8 months

The above results can be concluded that the PSA level of 8 months has a significant effect on the prognosis of mHSPC patients, and patients with PSA can be reduced to less than 0.
2 ng/ml have a more significant rPFS and OS benefit
.

Post-analysis of ARCHES studies:

The overall survival of mHSPC patients who received ADT treatment and whose PSA dropped to different levels before ^{enrolment[2].}

In the ARCHES study, more than 90% of mHSPC patients received ADT prior to enrollment and achieved varying levels of PSA (≤0.
2 μg/L, 0.
2−4 μg/L, and >4 μg/L).


Among them, a total of 1045 patients who had received ADT before enrollment, the median treatment time was 1.
6 months, 133 patients had a PSA ≤ 0.
2 μg/L, 372 PSA 0.
2-4 μg/L, and 540 > 4 μg/L
.

In this post-mortem analysis, the differences
in OS between Enza combined ADT and ADT in patients receiving ADT before enrollment were observed and compared in the three PSA groupings according to PSA groupings that reached different levels.

The results showed (Figure 2) that three groups of patients with ADT treatment with PSA≤0.
2 μg/L, PSA 0.
2-4 μg/L, and > 4 μg/L showed a longer OS benefit with enzaluride plus ADT treatment than ADT alone, and the risk of death was reduced by 52%, 46%, and 35%,
respectively.

Figure 2 OS results (A: ≤0.
2 μg/L, B: 0.
2−4 μg/L, C: >4 μg/L)

The above results show that mHSPC patients who have previously received ADT treatment and whose PSA can be reduced to less than 0.
2 ng/ml can still bring them longer survival benefits
by receiving intensive treatment.

Expert reviews

mHSPC refers to metastatic prostate cancer that has a therapeutic effect on ADT^[3
].

Once prostate cancer metastasizes, if not treated in a timely and effective manner, it will rapidly progress to the terminal mCRPC stage of prostate cancer, and the survival time of patients will be greatly shortened, so delaying the progress of mHSPC patients to the castration resistance stage and thereby prolonging the survival of patients is an important treatment strategy ^[4].


Since 2015, a growing number of ADT-based combination regimens have emerged in the mHSPC phase, which can significantly delay patient progression and thereby extend overall survival, including docetaxel chemotherapy and novel endocrine therapies such as abitron and apatamide ^{[5, 6, 7].}


In the actual clinical diagnosis and treatment process, clinical experts will also have some questions, including whether the better PSA control means that the patient's survival benefit is longer.
Was the previous use of ADT alone to treat well-controlled PSA, and the immediate transition to novel endocrine combination therapy, further prolong their survival? The latest findings at this ESMO conference give us some tips
.

PSA has always been one of the most concerned indicators for both clinicians and patients in the treatment of prostate cancer, as early as the 2006 SWOG 9346 study began to explore the relationship between the level of PSA decline and the overall survival of patients, and the study found that the overall survival benefit of patients with PSA drop below 0.
2 ng/ml was more significant ^[8].


The same results were found in later CHARRTED studies[5], LATITUDE studies[6], TITAN studies^[7], and PEACE-1 studies published at this conference, where mHSPC patients receiving docetaxel chemotherapy or novel endocrine therapies such as apatamide and abidolone were able to achieve PSA drops of 0.
2 ng/ Below ml, overall survival is further extended, and overall quality of life is better than in patients with a lack of deep PSA decline ^[9
].

So what are the advantages and disadvantages of several existing combination treatment options to reduce PSA to 0.
2 ng/ml? In a real-world study last year, apatamide showed that patients treated with mHSPC had a higher proportion of PSAs falling to <0.
2 ng/mL than abiraterone and enzalumide ^[10].


These results suggest that in the process of treating mHSPC patients, whether the patient's PSA level can drop to 0.
2ng/ml deserves our attention, and choosing a treatment plan that is more likely to reduce PSA to less than 0.
2ng/ml can further extend the patient's survival time while ensuring their quality of
life.

In the actual clinical diagnosis and treatment process, mHSPC patients need to consider not using new endocrine drugs after diagnosis, and may not be able to obtain new endocrine drugs for a while and use ADT first; Or the doctor may first use ADT to verify that the patient is sensitive enough for endocrine therapy, then it brings us a question for the clinical treatment of prostate cancer, that is, in patients who have only used ADT treatment in the past, if the PSA can be controlled below 0.
2ng/ml, then do we still need to combine with new endocrine therapy? This ESMO conference is a good answer for us, previously received ADT treatment, no matter what level PSA drops (even if it falls below 0.
2ng/ml), intensive treatment combined with new endocrine therapy will bring greater survival benefits
to patients.

The latest international guidelines, EAU guidelines[11], and the NCCN guidelines^[12] also further highlight ADT-based combination therapy as the standard treatment strategy
for the mHSPC phase in the 2022 edition of the update.

In summary, in the clinical diagnosis and treatment process, mHSPC patients are treated with ADT first, regardless of what factors are used, and the PSA reduction is how to immediately switch to combined with new endocrine therapy in the case of conditions can bring greater survival benefits
.

Professor Luo Guangheng

Director of Department of Urology, Guizhou Provincial People's Hospital

Chief physician, third-level professor, doctoral supervisor

Guizhou Provincial Management Expert

Deputy Director of Guizhou Institute of Renal and Urinary Diseases

Vice Chairman of Urology Branch of Guizhou Medical Association

Leader of the tumor group of urology of Guizhou Provincial People's Hospital

Member of the Minimally Invasive Science Group of the Urology Branch of the Chinese Medical Association

Member of the American Society of Urology

He is a member of the Urology Branch of the Chinese Medical Doctor Association

Urinary Tract Repair at the Urology Branch of the Chinese Medical Doctor Association

Deputy leader of the collaboration group

Member of the Editorial Board of the Chinese Journal of Urology

Corresponding Editorial Board Member of Chinese Medical Journal

References

[1].
Abstract 1361MO, 2022 ESMO Congress

[2].
Abstract 1398P, 2022 ESMO Congress

[3].
2021 CSCO Prostate Cancer Guidelines

[4].
2021 Guidelines for the diagnosis and treatment of urological diseases in China

[5].
Sweeney CJ et al.
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.
N Engl J Med.
2015; 373:737-46.

[6].
Fizazi K, et al.
Lancet Oncol.
Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial.
2019; 20(5):686-700.

[7].
Chi KN et al.
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med.
2019; 381 (1):13-24.

[8].
Hussain M, et al.
J Clin Oncol.
2006 Aug 20; 24(24):3984-90.

[9].
Small EJ, et al.
Presented at ASCO-GU 2022.

[10].
Pilon D, et at.
Presented at AMCP Nexus; October 18-21, 2021.

[11].
EAU-EANM-ESTRO-ESUR-ISUP_SIOG-Guidelines-on-Prostate-Cancer-2022

[12].
NCCN guidelines prostate 2022 V3