Editor's Note: Prostate cancer is a common malignant tumor of the reproductive system, particularly affecting elderly men. Screening high-risk populations and tailoring treatment plans based on patient characteristics are crucial for improving cure rates and enhancing quality of life. Recently, the 2024 ASCO Annual Meeting unveiled numerous advancements in the treatment of prostate cancer. "Oncology Frontier" invited Dr. Fu Fu Zheng from The First Affiliated Hospital , Sun Yat-sen University to provide an in-depth analysis of these advancements and discuss the latest breakthroughs in prostate cancer. This article summarizes notable real-world research explorations and related poster presentations for readers.Learning from Others
Several prostate cancer poster studies of interest to surgeons were also presented at this year’s ASCO. One study analyzed the impact of capsular invasion on patients with localized prostate cancer. Results indicated that capsular invasion could predict metastasis-free survival (MFS) and was associated with poorer OS.
For high-risk localized prostate cancer, a study summarized the long-term prognosis of various neoadjuvant regimens (abiraterone, enzalutamide, abiraterone plus enzalutamide, abiraterone plus apalutamide). Results showed that neoadjuvant ARPI therapy before radical prostatectomy achieved an 83% 5-year MFS. Residual cancer burden (RCB) had high prognostic value for MFS, and RCB could guide neoadjuvant strategies for high-risk localized prostate cancer.
Tumor suppressor gene alterations may impact the prognosis of newly diagnosed mCSPC patients treated with ARPI or docetaxel. A real-world study indicated that mCSPC patients with RB1 and TP53 mutations had poorer OS when treated with ARPI or docetaxel compared to patients without these mutations, while PTEN mutations did not affect OS. Thus, RB1 and TP53 mutations could serve as prognostic markers in clinical trials to guide targeted or combination therapies to improve survival.
For 177Lu-PSMA-617 treatment strategies, a study analyzed the relationship between tumor genetics and prognosis in PSMA-positive mCRPC patients. Results showed that CDK12, MYC, and FGFR mutations were associated with PSA50 reduction after 177Lu-PSMA-617 treatment, while patients without PTEN, RB1, and TP53 mutations had better OS. Further research is needed to clarify treatment priorities for mCRPC patients.
Additionally, HRD scores can be judged by integrating scores of genomic LOH, TAI, and LST. HRD is commonly used in gynecological tumors, and this study explored HRD in the TALAPRO-2 clinical trial. Results showed that HRD scores correlated with the status of 12 homologous recombination repair defect genes (BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, FANCA, RAD51C, NBN, MLH1, MRE11A, CDK12) in ctDNA. Regardless of high or low HRD scores, talazoparib combined with enzalutamide provided greater rPFS benefits than enzalutamide alone.
mHSPC patients treated with ADT may experience treatment-related adverse events and reduced quality of life. Whether patients can stop treatment after achieving PSA targets to improve quality of life is currently under investigation. The previous EMBARK study suggested that if PSA <0.2 ng/mL at 36 weeks, treatment could be paused and restarted upon biochemical recurrence, reducing financial burden and side effects. The LIBERTAS study analyzed the efficacy of apalutamide combined with intermittent or continuous ADT in mHSPC patients, with the gender-neutral and transgender study ongoing.
Prospective phase II PROact study results showed 100% PSA50 response rate (30/30) and 96.7% PSA90 response rate (29/30). The objective response rate was 92.3% (12/13). Patients tolerated the combination regimen well, with common treatment-related adverse events (TRAE) being anemia. This study confirmed the efficacy and tolerability of olaparib combined with abiraterone and prednisone in mHSPC patients with HRR gene mutations.
The COBRA study evaluated the safety and efficacy of 64Cu-SAR-bisPSMA for biochemical recurrence in prostate cancer patients after definitive treatment. Results indicated that this detection method was safe and effective, identifying lesions in up to 80% of patients. These findings have significant clinical implications for guiding patient treatment choices.
ODM-209 is a CYP 11A1 inhibitor for mCRPC patients. The phase I dose-escalation study results of the STESIDES trial showed that the drug was effective in multi-line treated mCRPC patients, especially those with AR-LBD mutations, though it may cause targeted adverse reactions.
Furthermore, ASCO posters also presented the results of the first oral potent EZH2 inhibitor, tazemetostat. The phase I trial results in CRPC patients showed good activity and controllable safety for tazemetostat combined with enzalutamide in patients previously treated with enzalutamide or abiraterone.
A study analyzing relugolix results indicated that relugolix combined with docetaxel showed good safety and antitumor activity in mCRPC patients who progressed after abiraterone treatment, supporting relugolix combined with docetaxel as a new treatment option for such patients.
AI Applications in Prostate Cancer Pathology
This year’s ASCO also featured several prostate cancer studies applying the latest AI analyses. In pathology analysis, AI can reduce the workload of over 3,000 pathologists. For surgeons, AI can assist in tumor diagnosis, including tumor detection, diagnosis, Gleason scoring, molecular typing, and prognosis prediction. A retrospective, multicenter, diagnostic study found that AI models using whole-slide images to detect pathological lymph node metastases in prostate cancer achieved an AUC of 0.989, suggesting further clinical application of AI. Additionally, AI can optimize systemic treatment plans for prostate cancer patients by analyzing tumor characteristics, genetic information, physical conditions, economic factors, drug side effects, and potential risks.
The numerous advances in prostate cancer research presented at this year’s ASCO meeting hold promise for further clinical application, improving patient survival and quality of life, and bringing more benefits to patients.
Dr. Fu Fu Zheng
Chief Physician, Doctoral Supervisor, Postdoctoral Cooperation Supervisor Department of Urology, The First Affiliated Hospital , Sun Yat-sen University Visiting Scholar, Massachusetts General Hospital, Harvard University International Member of the American Urological Association (AUA) Member of the Urogenital Branch of the China International Exchange and Promotion Association for Medical and Healthcare Deputy Group Leader of the Prostate Cancer Group of the Urology Branch of Guangdong Medical Association Member of the Urology Branch of Guangdong Medical Doctor Association Member of the Urogenital Oncology Committee of Guangdong Anti-Cancer Association Standing Committee Member of the Urology Branch of Guangdong Society of Integrated Chinese and Western Medicine Standing Committee Member of the Oncology Branch of the Guangdong Urological Association Executive Editor of the Journal of Urology (Electronic Edition) Reviewer for the Chinese Journal of Experimental Surgery
