De-escalating Treatment for Bladder and Prostate Cancers

Treatment approaches for bladder and prostate cancers have undergone rapid evolution in the last few years. Some patients can now safely delay or avoid surgery entirely and preserve their quality of life with positive oncological outcomes. Here are some lessons Fox Chase Cancer Center researchers are learning about these de-escalation approaches.

Prostate Cancer, Active Surveillance and Focal Therapy

Active surveillance for prostate cancer has become a reality for more men in recent years, as diagnosis and risk stratification techniques have improved, said Alexander Kutikov, MD, FACS, chief of the Division of Urology and Urologic Oncology at Fox Chase.

“In the active surveillance cohort, with long-term follow-up, the chance of dying from untreated prostate cancer is one in a thousand, which is similar to the chances of dying from similar risk prostate cancer if it was treated.” Kutikov said.

Key points in favor of active surveillance include:

• Active surveillance is safe and patients will get treatment if it is truly needed.
• Patients can put off or forego side effects for a number of years without impacting their survival rate.
• Active surveillance gives patients the option for safer and better therapies in the future as the field rapidly changes

Recent advances, such as improved imaging with multiparametric MRI scans, genomic signature assessments, fusion-targeted biopsy technology, and transperineal biopsies, have helped optimize surveillance strategies. 

In select men, when treatment is needed, a novel option is focal therapy, which uses targeted tumor destruction to treat small volumes of localized, clinically concerning prostate cancer. Real-time transrectal ultrasound guidance allows close monitoring to avoid unneeded treatment to the normal prostate and surrounding structures, which minimizes the side effects of this therapy.

 Focal therapy has several benefits:

• Few side effects and minimal negative impact on urinary, bowel, and sexual function
• Fast recovery time and minimal blood loss
• It does not preclude future definitive treatment

Risk-Stratifying Bladder Cancer

While surgery is the current standard of care for muscle-invasive bladder cancer (MIBC), ongoing clinical trials are exploring the question of whether avoiding surgery or radiation altogether may be a safe alternative for select patients who have undergone neoadjuvant chemotherapy.

Fox Chase medical oncologist Daniel M. Geynisman, MD, is researching this idea in a study entitled, “A Phase II Trial of Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN BLADDER).” In an attempt to individualize therapy for each patient, researchers are applying a risk-adapted approach that identifies genetic mutations in cancer cells to predict whether chemotherapy will be effective in eliminating all cancer and preventing recurrence or metastases.

Study participants with promising biomarkers, who are also clinically disease-free after neoadjuvant chemotherapy, are put on an active surveillance protocol for close monitoring of their progress and are spared the quality-of-life side effects common with cystectomy or radiation.

“Developing predictive biomarkers to understand who does or does not respond to chemotherapy can let us apply our treatment recommendations in a more nuanced way.” Geynisman said, noting that neoadjuvant chemotherapy followed by surgery has been proven to improve survival and remains the gold-standard for all eligigble patients with MIBC.

Another study — “Assessment of Reliability of Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder at the Time of Radical Cystectomy” — is developing a risk stratification tool by learning why cystoscopies don’t always find MIBC, said study leader Kutikov.

The researchers are developing standardized cystoscopic inspection descriptions using a map and scoring system. They are also investigating whether biomarkers in patient urine could be used to identify those with MIBC (after neoadjuvant chemotherapy) who should therefore have radical cystectomies.

“We hope these RETAIN BLADDER and pT0 studies will give new perspectives on effective bladder cancer treatment and the traditional standard-of-care recommendations,” said Kutikov. “By combining clinical data with molecular or genomic data and taking a risk-balanced approach based on different genetic markers in muscle-invasive bladder cancer, our goal is to enable doctors to make smarter decisions with their patients about cystectomies and, when possible, spare them from the life-changing procedure.”

Key takeaways about bladder and prostate cancer treatment de-escalation:

1. Active surveillance approaches are safe for select patients because treatment can be delivered if the disease progresses.
2. Prostate cancer risk stratification is improving because of advanced imaging and innovative biopsy approaches.
3. Focal therapy for select patients with prostate cancer allows for more nuanced treatment calibration.
4. MIBC risk stratification is being developed through the analysis of cystoscopic limitations and presence or absence of particular biomarkers.
5. Neoadjuvant chemotherapy should always be considered in treating MIBC because it is linked to increased survival rates.
6. As MIBC biomarkers are identified, more nuanced treatment recommendations will be possible.
7. Quality-of-life side effects related to both prostatectomies and cystectomies can be delayed or avoided entirely in properly selected patients.