A Year in Review: Some of the Most Impactful Advancements in GU Oncology in 2023

As we enter the last week of 2023, I want to highlight the many breakthroughs and advancements that occurred or were presented within urologic oncology in 2023. Throughout all urologic malignancies, but particularly bladder and prostate cancer, several exciting developments are paving the way for more effective cancer therapy. This review will highlight some of the primary advancements identified within urologic oncology during 2023 and what we look forward to in 2024 within the genitourinary oncology space.

There are several trials and findings worth mentioning in prostate cancer. The question of infectious complications such as prostatitis, urinary tract infection, and post-biopsy sepsis has been a hotly debated topic among urologists in the diagnostic sphere. The ProBE-PC randomized clinical trial comparing transperineal to transrectal prostate biopsy was published in late 2023 in the Journal of Urology. In this trial, the authors evaluated and randomized over 700 patients to either transrectal or transperineal prostate biopsy.¹ Authors evaluated patients for 30-day infectious complications and noted no difference in composite infectious complications between the cohorts. Another study published in BMC Urology found interesting differences between the 2 modalities for prostate biopsy. Specifically, Dr. Lu and colleagues found that when comparing over 452 patients undergoing prostate biopsy, the transrectal cohort had an overall higher rate of cancer detection in patients with larger prostate volumes and higher stages of prostate cancer. In contrast, the transperineal cohort had better detection at lower stages of disease.²

As urologists delve further into finding minimally invasive techniques to treat localized prostate cancer, the realm of focal therapy in prostate cancer remains a key area for research in urologic oncology. In 2023, Dr. Nicoletti and colleagues published a large-scale meta-analysis comparing the various focal therapy techniques.³ An analysis comprising 124 studies primarily using high-intensity focal ultrasound (HIFU) or cryotherapy (amongst other modalities) had a rate of biochemical prostate cancer recurrence (BCR) varying from 0-67.5%, according to commonly used Phoenix criteria for BCR.

The role of focal therapy within prostate cancer is not yet the standard of care as there are still large-scale randomized trials comparing existing modalities to focal therapy. Therefore, the University of California Collaborative (UC-Squared) recently published a consensus statement on the state of focal therapy and advised on which patients are best suited for it.⁴ The primary consensus regarding focal therapy from the Collaborative is that it is still investigational for prostate cancer treatment, and patients undergoing focal therapy should be included in investigational trials. Furthermore, the ideal patient for focal therapy has favorable intermediate- or low-volume unfavorable intermediate-risk disease with a low clinical stage.⁴ For treatment, the consensus group recommends that all patients have high-resolution prostate MRI and biopsies prior to consideration of focal therapy and those patients that undergo focal therapy should be regularly reassessed with PSA and follow-up prostate biopsy within 12 months.⁴ Further information regarding the consensus statement can be seen in the publication.

Finally, within the advanced prostate cancer space, there were several exciting announcements at ESMO Congress 2023 and 2023 ASCO® Annual Meeting; however, the use of radioligand therapy, particularly with ¹⁷⁷Lu-PSMA-617, continues to evolve and show promise. For example, a recent study observed the use of ¹⁷⁷Lu-PSMA-617 therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) that have not undergone chemotherapy. In this trial, the authors demonstrated that ¹⁷⁷Lu-PSMA-617 showed preferential improvement in radiographic progression-free survival (rPFS) compared with patients who switched to an alternative androgen receptor pathway inhibitor (ARPI).⁵

Regarding bladder cancer, several exciting developments in 2023 will undoubtedly improve patient care. Enfortumab vedotin (Padcev) is an antibody-drug conjugate (ADC) designed to deliver an MMAE agent that disrupts microtubules within cancer cells harboring the nectin-4 receptor.⁶ At ESMO 2023, groundbreaking data were published from the EV-302 (NCT04223856)⁷ trial comparing EV plus pembrolizumab (EV+P) to standard chemotherapy for metastatic urothelial carcinoma, demonstrating substantial overall survival (OS) and progression-free survival (PFS) benefits over the chemotherapy arm. Patients on the EV+P arm had nearly twice the metastatic PFS (12.5 vs 6.3 months) compared to the chemotherapy arm. Furthermore, the median OS in the EV+P arm was 31.5 months, double that of the chemotherapy arm at 16.1 months (p<0.0001).⁸ This breakthrough in therapy for patients with metastatic UC was further augmented by the fact that EV+P is a therapeutic combination that can be utilized in the setting of renal insufficiency—a common issue encountered with advanced bladder cancer patients.

As we stand on the cusp of 2024, the future of urologic oncology and cancer care remains bright. Specialists from all divisions, including urology, medical oncology, and radiation oncology, combined with our industry partners and researchers, continue to push the bounds of existing cancer care to improve patient outcomes.

Akhil Abraham Saji, MD, Fellow at the University of Southern California, is a urologist specializing in minimally invasive surgery and urologic oncology with an interest in technology-driven innovation within health care.

References

1. Mian BM, Feustel PJ, Aziz A, et al. Complications Following Transrectal and Transperineal Prostate Biopsy: Results of the ProBE-PC Randomized Clinical Trial. Journal of Urology. 2023;0(0):10.1097/JU.0000000000003788. doi:10.1097/JU.0000000000003788
2. Lu M, Luo Y, Wang Y, Yu J, Zheng H, Yang Z. Transrectal versus transperineal prostate biopsy in detection of prostate cancer: a retrospective study based on 452 patients. BMC Urol. 2023;23:11. doi:10.1186/s12894-023-01176-y
3. Nicoletti R, Alberti A, Castellani D, et al. Oncological results and cancer control definition in focal therapy for Prostate Cancer: a systematic review. Prostate Cancer Prostatic Dis. Published online July 28, 2023. doi:10.1038/s41391-023-00699-7
4. Javier-DesLoges J, Dall’Era MA, Brisbane W, et al. The state of focal therapy in the treatment of prostate cancer: the university of California collaborative (UC-Squared) consensus statement. Prostate Cancer Prostatic Dis. Published online August 8, 2023:1-3. doi:10.1038/s41391-023-00702-1
5. Sartor O, Gauna DEC, Herrmann K, et al. LBA13 Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore). Annals of Oncology. 2023;34:S1324-S1325. doi:10.1016/j.annonc.2023.10.085
6. Alt M, Stecca C, Tobin S, Jiang DM, Sridhar SS. Enfortumab Vedotin in urothelial cancer. Therapeutic Advances in Urology. 2020;12:1756287220980192. doi:10.1177/1756287220980192
7. Astellas Pharma Global Development, Inc. An Open-Label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. clinicaltrials.gov; 2023. Accessed December 31, 2022. https://clinicaltrials.gov/study/NCT04223856
8. KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Death by More Than Half Versus Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. Merck.com. Accessed October 26, 2023. https://www.merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-reduced-risk-of-death-by-more-than-half-versus-chemotherapy-in-patients-with-previously-untreated-locally-advanced-or-metasta/