New Developments in Prostate Cancer – Society of Urologic Oncology Meeting 2023

Prostate cancer remains one of the most complex areas of modern oncology, while also offering one of the widest ranges of treatment options. This complexity drives a continuing search to understand and develop better treatments and risk-stratification strategies.

The 2023 Society of Urologic Oncology (SUO) Annual Meeting featured studies revealing important advances. New insights into risk stratification and novel treatments for prostate cancer have the potential to transform both clinical practice and treatment approaches.

This article examines 3 important studies presented at SUO 2023 that highlight advances in prostate cancer treatment.

1. One study showed that magnetic resonance (MR) imaging -guided transurethral ultrasound ablation (TULSA) could provide disease control for up to 5 years in patients with localized (early-stage) prostate cancer.
2. Another study found that the radiopharmaceutical 225Ac-J591 (actinium therapy) could produce responses at metastatic sites in patients with metastatic castration-resistant prostate cancer (mCRPC).
3. And a fourth study suggested that artificial intelligence (ChatGPT) could not yet accurately risk-stratify patients with prostate cancer.

Long-Term Outcomes with TULSA

TULSA (transurethral ultrasound ablation) is a minimally invasive, MR-guided treatment for prostate cancer. It targets cancerous tissue with ultrasound waves and destroys it using high-frequency heat.

Study Details

At SUO 2023, researchers reported 5-year TULSA outcomes from the TACT trial. It included 115 patients with low-risk (33%) or favorable intermediate-risk (67%) T1 (77%) or T2 (23%) prostate cancer.

Researchers found that whole-gland TULSA provided durable disease control, had a favorable side-effect profile, and was associated with a low rate of subsequent treatment.

Results

• At 5 years, median prostate-specific antigen (PSA) remained low at 0.63 ng/mL. Median PSA had fallen from 6.3 ng/mL at baseline to 0.53 ng/mL at one year.
• The 5-year biochemical recurrence-free survival rate was 86%, and overall survival was 99%.

These results are exciting because there had been reservations about the effectiveness of focal treatments and criticism of insufficient long-term outcomes. Other treatment options have abundant long-term data, and similar evidence is now becoming available for TULSA. This is an important development for the field.

The study focuses on ablation (destruction) of the entire prostate gland. In the future, however, oncologists are expected to favor targeting only half the prostate or the areas containing tumors. This more focused approach requires additional long-term TULSA data.

Although TULSA appears somewhat less effective at completely eliminating cancer than surgery or radiation, a large proportion of clinically significant cancers were successfully eradicated. This makes the 5-year outcomes generally favorable and highlights TULSA's potential. Such developments may help reassess and improve prostate cancer treatment strategies.

TACT is a comprehensive trial providing important findings on TULSA. By the end of five years, 25 patients had received salvage treatment: 10 underwent radical prostatectomy (prostate surgery), 11 received radiotherapy, 3 received radiotherapy and androgen deprivation therapy, and 1 received both radiotherapy and radical prostatectomy.

Early predictors of salvage treatment were rising PSA during the first year and lesions seen on multiparametric MR imaging.

Patients most likely to benefit from TULSA were identified as those with intermediate-grade focal or regional tumors not close to the urethra or prostate apex. Large prostate calcifications may obstruct TULSA ablation waves, but small calcifications were not considered an obstacle.

The trial showed fewer side effects with TULSA than those commonly associated with surgery and radiotherapy. No grade 4 or higher side effects were attributed to TULSA, and no rectal injuries or fistulas were observed. Grade 3 side effects resolving within one year and side effects arising and resolving between one and two years were recorded. Erectile dysfunction and urinary incontinence were also reported at rates of up to 25%.

TULSA has had FDA approval for “marketing” in the United States since 2019, and most insurers cover the procedure. However, its effectiveness and toxicity rates remain under investigation.

The ongoing CAPTAIN trial compares TULSA with radical prostatectomy. It provides important data to help us better understand and assess prostate cancer treatment options.

Meaningful Responses in Visceral Metastases with Actinium Therapy

Another study presented at SUO 2023 reported findings from a phase 1 trial of 225Ac-J591. This treatment uses the anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591, labeled with radioactive actinium-225, which emits alpha particles. It is known as actinium therapy.

Between 2017 and 2020, 32 patients with metastatic castration-resistant prostate cancer (mCRPC) received 225Ac-J591.

• Among 20 patients with at least two PSMA-PET scans and response assessments, the molecular response rate was 35% and the biochemical response rate 30%; all were partial responses.
• Researchers analyzed responses by metastatic site, evaluating 144 bone, 69 lymph-node, and 21 visceral metastases. Response rates were 71% in visceral lesions, 52% in bone, and 39% in lymph nodes. Complete response rates were 9%, 7%, and 4%, respectively.

These findings are somewhat surprising by conventional understanding, as bone and visceral lesions are considered harder to treat than lymph-node lesions. They demonstrate the effectiveness of actinium therapy, one of two radionuclide treatment options available for advanced prostate cancer. The other is lutetium therapy. Optimal use of both remains a focus for improving outcomes.

These radiopharmaceutical treatments face practical challenges, including radioisotope availability, supply-chain logistics, and cost. We also lack sufficient knowledge of potential resistance to these radioisotopes.

The key to actinium therapy is the ability of alpha-particle-carrying antibodies to target prostate cancer cells accurately. If the right alpha particle reaches the right cancer cell, its size and destructive effect can lead to cell death. This is considered a new, promising approach to prostate cancer treatment.

Artificial Intelligence and Risk Stratification

A presentation at SUO 2023 showed that the artificial intelligence chatbot ChatGPT could not fully accurately risk-stratify prostate cancer patients.

ChatGPT was tested using data from 60 patients diagnosed with localized prostate cancer who had undergone prostate biopsy. A urologic oncologist classified their risk according to the National Comprehensive Cancer Network (NCCN) guidelines in the United States.

Researchers asked ChatGPT to classify the patients using the NCCN risk-stratification algorithm and each patient's clinical and histological characteristics.

ChatGPT misclassified 35% of patients (21 patients) and correctly classified 65% (39 patients). All misclassified patients were mistakenly placed in adjacent risk categories; for example, very-high-risk patients were classified as high risk.

It correctly assigned 14 patients to the intermediate-risk group, but did not divide them into favorable and unfavorable subgroups without further prompting. After additional guidance, 12 were correctly categorized.

Researchers also asked ChatGPT to suggest further evaluation and initial treatment. Despite sometimes identifying the wrong risk category, it successfully recommended appropriate treatment and imaging options for a given risk group.

However, because of ChatGPT's overall “poor performance,” researchers emphasized that trained healthcare professionals must support AI use in clinical decision-making. They also highlighted the need to consider the consequences of incorrect assessments when integrating AI into clinical tools. This illustrates potential limitations and important considerations in healthcare AI.