The evidence for active surveillance is stronger, but advances in imaging have improved the ability to distinguish between indolent and aggressive forms of prostate cancer.
Prostate cancer treatment and management have significantly improved and evolved in recent years, and several options are available depending on the stage and severity of cancer.
For localized prostate cancer, treatment options may include surgery, radiation therapy and active surveillance, which involves monitoring cancer without immediate treatment. For advanced prostate cancer, treatment options may include hormone therapy, chemotherapy, immunotherapy and targeted therapy.
Andres Correa, M.D., assistant professor and urologic oncologist at Fox Chase Cancer Center in Philadelphia, notes that the 15-year outcome results of the ProtecT trial have drawn a great deal of attention.
“The clinical trial aimed to assess if there was a difference in overall and cancer-specific survival in men with low-risk and intermediate-risk prostate cancer managed with either surgery, radiation or active monitoring,” he says. “The 15-year results showed no difference in prostate-cancer specific or overall survival between the three groups. Importantly, the trial demonstrated the overall very high survival rates of men with low-risk/intermediate-risk prostate cancer regardless of the treatment group.”
The study revealed that the use of active treatment (radical pros- tatectomy or radiation therapy) did reduce the incidence of metastatic disease and local progression and the need for long-term androgen deprivation therapy by approximately 50%, but these reductions did not translate into an improvement in mortality at 15 years.
“The use of active monitoring or active surveillance (AS) has been advocated for the management of men with low-risk prostate cancer for the last 15 years,” Correa says. “Although over-whelming data exist on its overall safety, the use of AS in the U.S. remains low. In the last query of the AUA AQUA (American Urological Association Quality Registry) data set, only around 60% of patients with low-risk disease are being managed with AS. While there has been steady improvement over the years, our European colleagues managed up to 90% of their low-risk patients under an AS protocol.”
He believes that the results of ProtecT will help increase the number of men with low-risk disease who are managed with AS and thus avoid the side effects associated with active treatment (radical prostatectomy/radiation therapy).
Moreover, the ProtecT trial showed that a subset of patients with intermediate-risk prostate cancer could be safely managed with AS, with very low long-term mortality rates.
Since 2011, Seth Blacksburg, M.D., senior vice president and chief medical officer at Accuray, has devoted much of his clinical focus to treating men with prostate cancer with various forms of radiation, including brachytherapy, image-guided radiation therapy, and stereotactic body radiation therapy (SBRT), and have been fortunate to participate in the care of over 2,000 patients.
He notes one of the biggest trends in prostate cancer involves utilizing precision in deciding when and how to deliver personalized care, citing the ProtecT study as well.
“It shows us that when managing a new diagnosis of prostate cancer, which includes active surveillance, surgery and radiation, there is a need to balance the benefits and harms of each treatment,” Blacksburg says. “Since the days of patients being enrolled on ProtecT, there are modern technologies that are helping us better understand how aggressive a new diagnosis of prostate cancer is, with better granularity. This includes the use of multiparametric MRIs, prostate-specific membrane antigen (PSMA) PET (positron emission tomography) and CT scans, image-targeted biopsies and molecular prognostic tests, which have all improved our ability to detect disease, differentiate indolent from aggressive prostate cancer and guide modern therapeutic pathways.”
Regarding treatment, modern prostate cancer treatment continues to evolve toward the use of fewer, more precise treatments. Blacksburg notes that this began with a transition from nine weeks of radiation to four or five weeks and is gravitating quickly toward a -day
“Research suggests that prostate cancer cells have a unique radiobiology that makes them highly sensitive to the amount of radiation dose delivered per fraction or treatment session,” he says. “This has led clinicians to consider hypofractionated schedules — the delivery of a higher dose per fraction in fewer fractions — compared with conventional, lengthy radiation schedules. SBRT, which combines a high degree of targeting accuracy with high doses of extremely precise, externally delivered radiation over four to five sessions, provides an optimal solution for accomplishing this goal.”
While a large body of scientific evidence exists on the use of SBRT to treat prostate cancer, Blacksburg believes two recent studies, PACE-A and PACE-B, have the potential to significantly impact clinical practice.
He notes that the PACE-A study randomly assigned men with low-
intermediate risk prostate cancer to receive treatment with surgery (mostly robotic) versus SBRT (mostly CyberKnife) and showed nearly half (46.8%) in the surgery arm wore pads at 2 years compared with 4.5% in the arm receiving SBRT. There was also a higher rate of sexual decline in those undergoing surgery compared with a higher bowel bother rate in those receiving SBRT.
“The PACE-B study (randomly assigned) men with low-intermediate prostate cancer to conventional radiation therapy versus SBRT and found that side effect rates were overall similar, though SBRT was delivered in five sessions while conventional radiation therapy was delivered in 20 or 39 sessions,” Blacksburg says. “A subgroup analysis was performed between CyberKnife and linac-based SBRT and showed less urinary and rectal side effects when patients were treated with the CyberKnife platform.”
What’s clear from these studies is that men screened for prostate cancer appear overall to have a low rate of death from disease and that balancing the risks of disease with the burden of treatment is of paramount importance.
Luke Chen, M.D., a medical oncologist and hematologist specializing in prostate cancer at City of Hope Orange County’s Huntington Beach and Irvine Sand Canyon locations in California, has been treating people with cancer for nearly 20 years.
“City of Hope’s focus is on therapies that shorten treatment plans and are more effective, such as hypofractionated radiotherapy that delivers higher doses of radiotherapy in fewer sessions, allowing patients to resume daily life sooner,” he says. “New technologies like TomoTherapy and TrueBeam machines also offer greater accuracy. At City of Hope, we use both machines to determine the best way to give maximum radiation to the prostate while minimizing radiation to nearby tissues like the bladder, bowel and rectum.”
City of Hope is also researching nonradiation techniques, such as MRI-
focused ultrasound, which was recently FDA approved to treat metastatic bone cancers and has potential for prostate cancer treatment.
“This approach heats and destroys targeted tissue areas without incisions, avoiding damage to healthy tissue,” Chen says. “It offers new options for patients whose cancer has returned after traditional treatments have failed or who cannot tolerate surgery or additional conventional treatment.”
The role of nuclear medicine in the diagnosis and treatment of prostate cancer is expanding. Traditionally, its use was mostly limited to less precise scans to assess whether prostate cancer may have spread to bones. Now it can help more accurately stage prostate cancer when it is first diagnosed and, if it recurs, better identify treatments that will more precisely manage disease.
Over the last two years, PSMA PET agents, such as with the use of gallium-68 PSMA PET imaging, have been introduced into the U.S. market following FDA approval. PSMA agents are directed toward a prostate-specific cell membrane glycoprotein that is overexpressed in prostate cancer. To date, PSMA is the most sensitive marker for the detection of extra-prostatic disease, allowing for improved staging and
“I believe that the introduction of PSMA PET has allowed us to better define the high-risk patients that would benefit from radical prostatectomy as compared to radiation with androgen deprivation therapy (ADT),” Correa says. “The role of radical prostatectomy in the majority of high-risk patients is to avoid the use of ADT, which only occurs if the patient is able to have an undetectable PSA after surgery.”
In the past, Correa explains, some of these patients would have a detectable prostate-specific antigen (PSA) for which they would end up having radiation and ADT.
“The addition of PSMA has allowed us to better find patients with low-volume metastatic disease (typically not detected with conventional imaging such as CT/bone scans) that we know are not going to benefit from a radical prostatectomy,” he says.
Nuclear medicine, in the form of radiopharmaceuticals, also provides an additional treatment option for some men with prostate cancer. Radiopharmaceuticals are a class of therapeutic agents designed to specifically target and kill cancer cells that have spread to the bones, while sparing normal tissues.
“Radium-223, an alpha-emitting radiopharmaceutical that targets areas of increased bone turnover, such as bone metastases, has been used for many years in the management of certain metastatic prostate cancers,” Blacksburg says. “Another radiopharmaceutical currently being used is lutetium-177 (PSMA) radioligand therapy. This agent targets the PSMA protein, which is highly expressed on prostate cancer cells, and has shown extremely promising results.”
Munir Ghesani, M.D., systems chief of nuclear medicine at Mount Sinai Health in New York and president of the Society of Nuclear Medicine and Molecular Imaging, routinely sees prostate cancer patients for consults for treatments with the targeted radiopharmaceutical therapies when the cancer has spread outside the prostate and when other therapies are no longer effective.
“Targeted radiopharmaceutical nuclear medicine therapies are a game changer,” he says. “When used in the appropriate setting, they slow down progression of cancer, (improve) quality of life and prevent complications from advanced cancer. They have even shown to improve survival when compared to other therapeutic modalities in these settings.”
This method has evolved considerably after what he calls “remarkable success” of a clinical trial whose results were presented at the 2021 American Society of Clinical Oncology Annual Meeting. Those favorable esultswhich led to an approval of Lu-177 PSMA, the first targeted radiopharmaceutical nuclear medicine therapy for patients with advanced prostate cancer who no longer respond to hormone therapy and who continue to progress despite chemotherapy.
Blacksburg feels that prostate cancer treatments will continue to improve through a combination of technological advancements, personalized medicine and clinical research.
“By leveraging these tools and approaches, we can provide better care for patients with prostate cancer and ultimately improve their outcomes and quality of life,” he says. “Advances in imaging technology, such as better CT, MRI and PET scans to detect cancer cells, will enable earlier detection and more precise staging of prostate cancer.”
Additionally, the continued development of personalized medicine will play an important role in improving prostate cancer treatment.
“With the increasing availability of genomic testing and targeted therapies, we can better understand the molecular characteristics of individual tumors and tailor treatment to the unique needs of each patient,” Blacksburg says. “This personalized approach will likely result in improved treatment outcomes and fewer side effects. Finally, clinical research will continue to drive progress in prostate cancer treatment. Clinical trials evaluating new drugs and treatment approaches are ongoing, and the results of these studies will guide clinical practice in the years ahead.”
Keith Loria is a freelance writer in the Washington, D.C., area.