Malić Vončina S, Stenqvist A, Bungum M et al: Sperm DNA fragmentation index and cumulative live birth rate in a cohort of 2,713 couples undergoing assisted reproduction treatment. Fertil Steril 2021; 116: 1483–1490.

Special thanks to Drs. Kareim Khalafalla and Samuel Ohlander at the University of Illinois at Chicago.

Controversy remains on the relationship between sperm DNA fragmentation index (DFI) and assisted reproductive technique (ART) success. These authors sought to investigate the single, first cycle cumulative live birth rates between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in cohorts of low or high DFI. The unique approach of using cumulative live birth rates allowed the evaluation of the number of live births that resulted from a single fertilization and culture cycle that included both fresh and frozen embryo transfers. The authors asserted that cumulative live birth rate offers a more clinically relevant outcome for ART decision making.

A total of 2,713 couples who underwent 5,422 ART cycles between 2007 and 2017 were included. Couples were divided based on the ART method of their first cycle, IVF or ICSI. Based on previously published data, the authors used a threshold of 20% DFI measured by sperm chromatin structure assay to separate normal and abnormal. The cumulative live birth rate was significantly higher in the IVF group with normal DFI compared to high DFI, while in the ICSI group, no statistical significance was noted between the DFI subgroups. Moreover, high DFI had a significant negative effect on fertilization rate in the IVF group, while no association was reported with the ICSI group.

The authors noted the importance of DFI levels in IVF success and concluded that DFI analysis could be routinely considered in deciding the best ART method that a couple will undergo to improve the overall treatment outcome. This is a large study, and I’m not completely sold yet on the idea, but another confirmatory study or 2 would go a long way toward selling it to me.

Chappidi MR, Yang H, Meng MV et al: Utility of blue light cystoscopy for post-bacillus Calmette-Guérin bladder cancer recurrence detection: implications for clinical trial recruitment and study comparisons. J Urol 2022; 207: 534–540.

Special thanks to Drs. Susan Talamini and Daniel Moreira at the University of Illinois at Chicago.

Previous studies have demonstrated the utility of blue light cystoscopy in detection of primary bladder tumors and tumor recurrence as compared to white light cystoscopy alone.¹ Less well known is the utility of blue light cystoscopy in the surveillance for nonmuscle-invasive bladder cancer in those undergoing bacillus Calmette-Guérin (BCG) therapy. The authors sought to determine if blue light improved recurrence detection rates in patients with nonmuscle-invasive bladder cancer through the first year of BCG therapy.

Using the prospective Cysview^® Registry, which encompasses patients undergoing surveillance cystoscopy using both white and blue light cystoscopy at 13 academic centers and in 1 community setting, they identified 282 patients who received BCG within a year. Recurrence was 45% overall. Of these, 87.4% were detected with white light. Without blue light cystoscopy, 12.6% of the total recurrences would not have been detected. The authors observed that of all patients who had a reported negative white light cystoscopy, indicating what was considered as a complete response to BCG, 9.4% had a recurrence detected on blue light, and this rate corresponded with rates found in similar studies. The false-positive biopsy rate with blue light was 5.3%.

While recommendations regarding use of blue light in patients undergoing BCG therapy currently rely on expert opinion, there are no formal guidelines. This study adds to the growing evidence validating the utility of blue light in these patients. Providers should consider using blue light cystoscopy in the first year of post-BCG cystoscopies after discussing the risk of false-positives.

Smith MR, Hussain M, Saad F et al; ARASENS Trial Investigators: Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 2022; https://doi.10.1056/NEJMoa2119115.

Special thanks to Drs. Hari Vigneswaran and Daniel Moreira at the University of Illinois at Chicago.

Survival for metastatic prostate cancer improves dramatically with androgen deprivation. Overwhelming high-level evidence now suggests that additional therapy with chemotherapy such as docetaxel or an androgen-receptor pathway inhibitor such as abiraterone, enzalutamide, or apalutamide improves survival. This begs the question, is more better? Thus far, phase 3 trials of combination therapy with androgen-receptor pathway inhibitor, androgen deprivation therapy, and docetaxel have shown conflicting results.

In the international, randomized, double-blind, placebo-controlled clinical ARASENS trial, a total of 1,306 men with metastatic hormone-sensitive prostate cancer were randomized in a 1:1 ratio to receive androgen deprivation plus docetaxel and darolutamide or androgen deprivation plus docetaxel and placebo. The primary endpoint was overall survival. The median followup was 44 months for the darolutamide group and 42 months for placebo. All subjects had overall good functional status with ECOG (Eastern Cooperative Oncology Group) scores 0 to 1. The median age was 67 years. The overall survival at 4 years was 63% in the darolutamide group compared to 50% in the placebo group, with a 33% lower risk of death in the darolutamide arm. There were no differences in high-grade adverse effects.

To summarize, among men with metastatic, hormone-sensitive prostate cancer, overall survival was significantly improved with the combination of androgen deprivation, docetaxel, and darolutamide. This study showed that, yes, more is better, and combination therapy was beneficial in this setting.