Preface
On April 26-27, 2024, the 2024 CSCO Guidelines Meeting, co-sponsored by the Chinese Society of Clinical Oncology (CSCO) and Beijing Heath Clinical Oncology Research Foundation, was held in Jinan. In the prostate cancer session, Professor Zhu Yao from Fudan University Cancer Hospital gave a detailed explanation and wonderful interpretation of the key points of the 2024 CSCO prostate cancer guideline update.
Surge in incidence Early screening and early diagnosis
In recent years, the incidence of prostate cancer in China has surged, the mortality rate is high, and the disease burden is heavy. Compared with the United States, the incidence and mortality of prostate cancer in China are low, but the mortality rate after the onset of prostate cancer is high, so early screening and early diagnosis are urgently needed. The results of long-term follow-up in the Chinese population also showed that regular PSA testing could reduce prostate cancer mortality.
Localized high-risk intensive treatment
Confined to high-risk patients: interpretation of new evidence for surgery and radiotherapy
For the optimal treatment modality for high-risk localized prostate cancer, a multicenter, prospective, long-term cohort study compared the long-term survival of patients with prostate cancer who received radical prostatectomy (RP), brachyradiotherapy (BT), external beam radiation therapy (EBRT), androgen deprivation therapy (ADT), active surveillance (AS)/wait-and-watch (WW). The results showed that after adjusting for age and comorbidities, prostate cancer-specific mortality (PCSM) was lower after local therapy in patients with high-risk prostate cancer, especially after curative surgery. Longer follow-up data will be needed for validation in the future.
In a study of patients with intermediate-risk prostate cancer undergoing RP and pelvic lymph node dissection (PLND), only 2.9% of intermediate-risk patients had lymph node metastases. In view of the lack of clear evidence of survival benefit for PLND, PLND may be omitted for safety considerations in intermediate-risk patients with PSMA-PET-negative patients. Expanded pelvic lymph node dissection (ePLND) can help provide accurate lymph node staging, and preoperative PSMA-PET is more accurate for staging prostate cancer, but both have the potential to miss lymph node metastases. Therefore, it is necessary to clarify the benefits and risks of PLND and PSMA-PET to patients before surgery, and to perform ePLND for high-risk localized or late-stage prostate cancer undergoing PLND. Patients should be aware that surgery is part of a multimodal approach before surgery.
The GETUG-AFU18 study suggests that 3-year long-term ADT combined with high-dose RT (80Gy) can prolong progression-free survival, cancer-specific survival, and overall survival of high-risk prostate cancer compared with conventional dose (70 Gy) radiotherapy, providing the latest evidence for the treatment of high-risk prostate cancer patients.
The RADICAL-RT study explored the timing of radiotherapy after radical prostatectomy, and the results showed that there was no significant difference in long-term FFMD and OS between the adjuvant radiotherapy group and the early salvage radiotherapy group after radical resection, and the incidence of adverse events of urological and intestinal diseases increased in the adjuvant radiotherapy group. Studies suggest that early salvage radiotherapy can be used for patients with biochemical recurrence (BCR) after radical prostatectomy.
Patients with biochemical recurrence: risk stratification for better treatment options
One cohort study explored the relationship between BCR and its risk stratification and PCSM after radical prostatectomy or radiotherapy. Studies suggest that patients with low risk of BCR after radical prostatectomy can consider immediate salvage therapy. The probability of BCR after radical prostatectomy is significantly higher, but the risk of dying from prostate cancer is higher after radiotherapy.
BCR is not a reliable predictor of PCSM and should not be used to compare treatment modalities. According to the EAU definition, the risk of death from prostate cancer after radiotherapy with low-risk BCR is relatively high, suggesting the need for stricter criteria. Risk stratification of BCR is essential to guide salvage treatment decisions, reduce overtreatment, and limit staging when PSA is elevated after initial therapy.
The EMBARK study is designed to evaluate the efficacy and safety of enzalutamide in combination with ADT or enzalutamide monotherapy in patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk BCR. The results showed that enzalutamide + ADT reduced the risk of metastasis or death by 58% compared with ADT alone. For patients with BCR who have progressed on maximized pelvic therapy, the NHA+ADT combination has improved the prognosis of patients, suggesting that intensive endocrine has progressed forward.
Update the scene to keep up with the times
mCSPC: Triple therapy data update, new evidence for bone-related events
The ARASENS study was designed to evaluate the efficacy of darolutamide versus placebo in combination with ADT and docetaxel in the treatment of mHSPC. The 2023 ASCO Congress updated OS results from the ARASENS study, with data showing that intensive therapy showed a trend toward prolonged OS in patients with high tumor burden (HR=0.69), high-risk (HR=0.71), and low-risk (HR=0.62). For patients with low tumor burden, the HR for OS was 0.68, but the upper 95% CI was 1.13, suggesting that patients with low tumor burden may not benefit from intensive therapy. In 2024, ASCO GU will be updated again to consider the patient's subsequent systemic anti-tumor therapy as a clinical outcome event. The data showed that the median duration to follow-up treatment was 49.0 versus 31.6 months in the darolutamide + docetaxel + ADT versus docetaxel + ADT groups (HR 0.47, 95% C1, 0.40-0.54, p<0.0001).
The PEACE-1 study is designed to evaluate the efficacy and safety of ADT + abiraterone + prednisone ± radiotherapy in metastatic castration-sensitive prostate cancer (mCSPC). Previous results have shown that the benefit of abiraterone intensive therapy regimen is mainly in people with high tumor burden, and no OS benefit has been observed for low tumor burden. The 2023 ASCO update results showed that radiotherapy + abiraterone + SOC improved rPFS in patients with low tumor burden (HR=0.65, p=0.02), but did not improve OS (HR=0.77, p=0.21).
Patients with mHSPC are often recommended for long-term ADT therapy, with an increased risk of bone loss and fracture as known complications. The AMPEDE study analyzed 1349 M1 patients and 796 M0 patients, and confirmed that the addition of zoledronic acid to ADT combined with DOC significantly reduced the incidence of fractures in M1 patients at 5 years. The data from this study provide support for the clinical use of zoledronic acid to combat bone loss in patients with mHSPC to reduce the occurrence of fracture events.
In addition, a multicenter, randomized phase 2 study confirmed that prophylactic radiotherapy improved bone-related events in patients with high-risk asymptomatic metastatic prostate cancer.
mCRPC: BRCAAway,PROpel,CONTACT-2等研究引发治疗变革
The BRCAAway study is a multi-cohort Phase II study investigating different first-line treatment modalities for PARPi or NHA, enrolling patients with treatment-naïve mCRPC (mHSPC-stage anti-androtherapy-naïved). The study suggests that in patients with BRCA1/2 or ATM-mutated mCRPC, olaparib plus abiraterone has better progression-free survival (mPFS 39 months) than olaparib (mPFS 14 months) or abiraterone (mPFS 8.4 months), and can be crossed over after progression in the monotherapy group and PFS2 is 16 months after crossover therapy, suggesting that early use of olaparib combination therapy may bring better survival benefits to patients.
PROpel, TALAPRO-2 and other studies have suggested that patients with BRCA/HRR mutations have more significant benefits from using PARP+NHA regimen, which has been strongly recommended by the 2024 EAU prostate cancer guidelines.
In the CONTACT-2 study, the only combination that suggests a benefit from immunotherapy, cabozantinib in combination with atezolizumab significantly improved rPFS compared with NHA in patients with mCRPC who have progressed on NHA and have extrapelvic lymph node or visceral disease.
Precise inspection and abundant choices
With the application of precision imaging technologies such as PSMA, the diagnostic accuracy of prostate cancer recurrence and metastasis has been significantly improved, and PSMA PET/CT can be considered for BCR patients to formulate a precise treatment plan, and for patients with nmCRPC, PET/CT-guided precision radiotherapy can prolong the metastasis-free survival time.
Editor: Faline
审校:Faline
Typesetting: Faline
Executive: Babel
This platform aims to deliver more medical information to healthcare professionals. The content published on this platform should not be used as a substitute for professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice. If such information is used for purposes other than understanding medical information, the platform does not assume relevant responsibilities. This platform does not mean that it agrees with its descriptions and views on the published content. If copyright issues are involved, please contact us, and we will deal with it as soon as possible.