ASTRO 2022 Science Highlights

This year’s annual meeting of the American Society for Radiation Oncology (ASTRO 2022) included several interesting articles about genitourinary cancer. Many of them focused on prostate cancer, but there also were some on bladder cancer. Gerard Morton, MB, BCh BAO, MRCPI, FFRRCSI, FRCPC, of Sunnybrook Odette Cancer Centre at the University of Toronto highlighted a few key abstracts of interest to clinicians.

In the realm of prostate cancer, Dr. Morton explained 3 themes of questions that the abstracts at ASTRO sought to answer: (1) In primary prostate cancer, how does hypofractionated radiation therapy compare to conventional radiation therapy in high-risk patients? (2) What is the role of high- dose rate (HDR) boost in brachytherapy for prostate cancer? (3) How does HDR compare to low-dose rate (LDR) boost?

PCS5 Clinical Trial Review

The first trial reviewed was the PCS5 clinical trial.¹ PCS5 is a phase 3 trial being conducted in Canada that focuses solely on patients with high-risk prostate cancer (stage >cT3a, prostate-specific antigen [PSA] >20, or Gleason grade 8-10) randomized to conventional or hypofractionated radiation therapy. The authors sought to evaluate early and late toxicity, as well as the secondary endpoints of overall survival (OS), disease-specific survival (DSS), distant metastases, and quality of life (QOL) factors. At the ASTRO meeting, the authors of the PCS5 trial presented data from the median follow-up of 7 years. In reviewing the patient characteristics, Dr. Morton confirmed that the trial had enrolled only patients with high-risk prostate cancer, with 49% having Gleason grade 8 disease and 34% having Gleason grade 9 to 10 disease.

Findings for the primary endpoint of the PCS5 trial demonstrated that hypofractionated primary radiation therapy was safe and noninferior to conventional radiation therapy. The authors reported similar rates of grade r2 gastrointestinal (GI) toxicity (hypofractionated vs conventional, 9% vs 8%) and genitourinary (GU) toxicity (2% vs 7%). Regarding the secondary endpoints, the authors presented Kaplan-Meier survival curves for OS and DSS that demonstrated near-identical oncologic outcomes, suggesting that hypofractionated radiation can be used safely in patients with high-risk prostate cancer. Dr. Morton remarked that the data offers support for clinicians utilizing hypofractionation in this setting.

Dr. Morton also reviewed the topic of brachytherapy by referencing the American Society of Clinical Oncology guidance that patients with intermediate- or high-risk prostate cancer should receive a brachytherapy boost.²

HDR Versus LDR Boost

At ASTRO 2022, Moideen et al presented a phase 3 trial investigating the role of HDR boost compared with LDR boost in prostate cancer brachytherapy.³ Specifically, the authors hypothesized that HDR boost would provide the same oncologic efficacy while improving QOL compared with LDR boost.

The authors enrolled 195 patients with a prostate volume <60 mL and low urinary symptom International Prostate Symptom Score (IPSS; <16) to either HDR boost or LDR boost categories. The primary and endpoints focused on QOL (Expanded Prostate Cancer Index Composite [EPIC] urinary, bowel, and sexual function scores at 6 months). Dr. Morton briefly reviewed the patient demographics of the trial cohort, which comprised primarily older patients (mean age, 71.1 years) most of whom had high-risk disease (57%).

He emphasized that the sequence of intervention differed between the 2 arms, primarily in that patients in the HDR boost arm received the boost before initiation of external- beam radiation therapy (EBRT) while patients in the LDR boost arm received the implantations shortly after completing EBRT. In reviewing the results, Dr. Morton demonstrated that patients in both arms saw decreases in urinary QOL, which subsequently recovered to baseline by 12 months; however, for GI QOL, patients receiving LDR had prolonged decreases in QOL that never recovered to baseline levels. Like urinary QOL, patients had similar sexual QOL scores, regardless of the boost mechanism used.

In conclusion, the data from this trial suggest that use of HDR boost facilitates improved early urinary QOL compared with LDR boost, although there is no difference later in the treatment course. HDR boost also seems to portend improved GI symptoms and QOL. Dr Morton emphasized that these findings must be taken in context considering that LDR radiation doses were overall higher and LDR has a long history of clinical efficacy that HDR boost lacks.

Bladder Cancer Trials at ASTRO 2022

ASTRO 2022 also offered pertinent updates on the management of bladder cancer. The 2 primary strategies for bladder preservation in the setting of muscleinvasive bladder cancer are trimodal therapy and partial cystectomy. Trimodal therapy consists of maximal transurethral resection of the bladder tumor combined with radiosensitizing chemotherapy agents and radiation therapy. Unfortunately, there have been no direct trials comparing the outcomes in patients undergoing trimodal therapy versus standard of care radical cystectomy.

Dr. Morton remarked that the SPARE trial⁴ attempted to answer this question but was hampered by patient nonadherence and reluctance to agree with randomization. To simulate the outcomes of a randomized controlled trial (especially as there are no planned future randomized trials to investigate these outcomes), Efstathiou et al compiled a multi-institutional comparison of radical cystectomy versus trimodal therapy.⁵

The comparison included a sizable patient population, with 834 patients in the radical cystectomy arm and 282 patients in the trimodal therapy arm. Dr. Morton remarked that both arms had similar patient characteristics in terms of age, percentage of carcinoma in situ (CIS)-positive disease, similar clinical stage including presence of hydronephrosis, and use of neoadjuvant chemotherapy. Patients receiving trimodal therapy had a 20.5% rate of non–muscle-invasive disease recurrence and 13% required salvage cystectomy. Patients who received upfront radical cystectomy had a perioperative mortality rate of 2.1%, with most having pT3 to pT4 disease (42%) at the final pathologic analysis. Evaluation of outcomes revealed some interesting findings. All outcomes generally favored the trimodal therapy arm. At a cut point of 5 years, metastasis-free survival favored trimodal therapy over radical cystectomy (78% vs 73%) although the difference was not statistically significant (P=0.07). Evaluation of cancer-specific survival (CSS) and OS also favored trimodal therapy with a statistically significant difference for both CSS (78% vs 85%; P<0.0001) and OS (66% vs 78%; P<0.001).

Dr. Morton remarked that the results of the trial were highly unusual, particularly in demonstrating that a nonsurgical technique is potentially superior to a surgical one. He concluded by noting these are potentially the best data available, suggesting that trimodal therapy may be equivalent to or even better than radical cystectomy, with the caveat that this was not a randomized prospective trial.

The articles on prostate and bladder cancer highlighted by Dr. Morton are of key clinical interest for all practicing clinicians. The program at ASTRO 2022 included several other important and thought-provoking scientific abstracts with oncologic outcomes that are also worth reviewing.

Akhil Abraham Saji, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include urology education and machine learning applications in urologic care. He is a founding and current member of the EMPIRE Urology New York AUA section team.

References

1. Niazi TM, Nabid A, Malagon T, et al. Conventional vs. hypofractionated, radiotherapy for high-risk prostate cancer: 7-year outcomes of the randomized, non-inferiority, phase 3 PCS5 trial. Int J Radiat Oncol Biol Phys. 2022;114(3):S3. Abstract 4. doi: 10.1016/j. ijrobp.2022.07.2323
2. Chin J, Rumble RB, Kollmeier M, et al. Brachytherapy for patients with prostate cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update. J Clin Oncol. 2017;35(15):1737-1743. doi: 10.1200/JCO.2016.72.0466
3. Moideen N, Crook JM, Araujo CD, et al. A randomized phase III Trial comparing health-related quality of life after low dose rate (LDR) or high dose rate (HDR) prostate brachytherapy boost combined with external beam pelvic radiotherapy (EBRT). Int J Radiat Oncol Biol Phys. 2022;114(3):S3-S4. Abstract 5. doi: 10.1016/j.ijrobp.2022.07.2324
4. Huddart RA, Birtle A, Maynard L, et al. Clinical and patient-reported outcomes of SPARE—a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int. 2017;120(5):639-650. doi: 10.1111/bju.13900
5. Efstathiou JA, Ballas LK, Niemierko A, et al. Multi-institutional matched comparison of radical cystectomy to trimodality therapy for muscle invasive bladder cancer (MIBC). Int J Radiat Oncol Biol Phys. 2022;114(3):S74-S75. Abstract 234. doi: 10.1016/j.ijrobp.2022.07.472