Emerging Therapeutic Landscape in Genitourinary Oncology
The field of genitourinary (GU) oncology has witnessed a paradigm shift with the advent of pioneering therapies for prostate, bladder, kidney, testicular cancer and penile cancers. These groundbreaking advancements, provide patients with a multitude of therapeutic options tailored to their individual needs and preferences.
Technological Innovations and Clinical Trial Research
Leading-edge technological advancements have paved the way for novel treatment approaches, including robotic-assisted surgery, high-precision radiotherapy techniques, focal therapy (cryosurgery, high-intensity focused ultrasound, irreversible electroporation), targeted molecular therapies, novel chemotherapeutic agents and immunotherapies. And, ongoing clinical trials continuously unveil discoveries, offering patients less invasive treatments and improved outcomes, while maintaining quality of life.
Surgical Paradigm Shift
Minimally invasive robotic-assisted laparoscopic surgery has transformed surgery and is the standard of care, largely supplanting traditional open surgical approaches in many instances. This burgeoning technology offers numerous advantages, including:
- Reduced surgical trauma and blood loss.
- Faster recovery times and shorter hospital stays.
- Improved cosmetic outcomes with smaller incisions.
- Enhanced visualization and surgical precision.
- “Nerve-sparing” technique that helps to improve functional outcomes (e.g., urinary continence, sexual function).
Novel Therapeutic Landscape
Androgen Deprivation Therapy (ADT) and Novel Hormonal Agents (NHA)
ADT continues to be the standard of care for metastatic prostate cancer. The inevitable development of castration resistance has been a therapeutic challenge. Abiraterone (Zytiga), approved in 2011, represents a novel hormonal agent that inhibits extragonadal androgen biosynthesis, offering an additional line of hormonal manipulation. Since then, several other androgen receptor pathway inhibitors (ARPIs) have been approved for use in prostate cancer at different stages – enzalutamide (Xtandi), apalutamide (Erleada) and darolutamide (Nubeqa). These treatments may also be combined with other therapies to improve efficacy.
Chemotherapeutic Agents
The taxanes, docetaxel (Taxotere), and cabazitaxel (Jevtana), have demonstrated survival benefits in metastatic prostate cancer (CRPC). Docetaxel is approved in both the castration-sensitive and resistant settings, while cabazitaxel is only approved for post-docetaxel use in the castration-resistant setting. Recent trials have also shown a benefit for combination therapy – ADT + NHA + docetaxel – as first-line treatment in the metastatic castration sensitive setting.
Targeted Molecular Therapies
Angiogenesis inhibitors like sorafenib (Nexavar), sunitinib (Sutent), and pazopanib (Votrient) paved the way for newer treatment options in advanced renal cell carcinoma. We now have several targeted agents used for treatment alone and in combination with immunotherapy, including axitinib (Inlyta), Lenvatinib (lenvima), and cabozantinib (Cabometyx).
In prostate cancer, mutation testing on both tumor tissue and the patient’s DNA has allowed for the detection of mutations in DNA-repair genes such as BRCA1/2, ATM, CHEK2, and others. Poly-ADP ribose polymerase (PARP) inhibitors are now approved for use in metastatic prostate cancer in patients who are found to have one of these mutations. Ongoing trials are evaluating molecular therapies targeting cell division and angiogenesis in bladder cancers as well.
Immunotherapy
Sipuleucel-T (Provenge), an autologous cellular immunotherapy, was approved in 2010 for metastatic CRPC, harnessing the patient's immune system against the malignancy. Checkpoint inhibitors blocking PD-1, PDL-1, and CTLA-4 are effective in many tumor types and are now standard of care. Within the field of GU cancer, these drugs including pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) are an essential part of the management plan for kidney and bladder tumors.
Precision Radiation Therapy
Focused, High-Dose Radiation Delivery
Novel technologies now enable dramatic dose escalation to improve long-term outcomes while minimizing exposure to adjacent healthy tissues like the bladder, bowel and rectum. Contemporary radiation modalities offer unprecedented precision and conformality.
Intensity-Modulated Radiation Therapy (IMRT)
By modulating the radiation intensity across different tumor sub-volumes, higher doses can be selectively directed to the gross disease while sparing surrounding organs at risk with lower doses at the periphery.
Image-guided Radiation Therapy (IGRT)
Given the prostate's mobility relative to the bladder and rectum, frequent positional verification is crucial before beam delivery. Many centers employ IMRT with 3D computed tomography (CT) guidance, aligning the beam to the patient's internal anatomy rather than relying on external surface markers. This meticulous attention to positioning ensures precise targeting with each fraction.
Accounting for Tumor Motion
Radiation oncology teams use sophisticated methods to position patients and track tumor motion when delivering high dose radiation. This is important to ensure accurate and precise targeting of the tumor and avoidance of normal surrounding tissue. Several GU tumors may move during treatment, such as a kidney cancer during respiration. A 4-dimensional (4D) CT scan creates a video of tumor motion which accounts for day-to-day variability when creating the radiation plan and minimizes target miss. Further, advanced radiation delivery with MRI-guidance or adaptive planning allows for real-time assessment of tumor motion and the opportunity to modify the radiation plan ‘on the fly’ based on daily changes in patient anatomy.
Stereotactic Body Radiotherapy (SBRT)
SBRT is an advanced modality that offers radio-surgical precision in extracranial sites. Physicians can sculpt the beam shape, intensity, and angle with exquisite control, enabling highly conformal dose delivery. SBRT facilitates significant hypofractionation, with ultra-high doses administered over just a week compared to conventional two-month courses. SBRT is used in various GU malignancies in both the localized and metastatic setting to optimize cure and stop tumor growth.
Brachytherapy
Brachytherapy provides a means of delivering radiation internally at the tumor site. It can be employed as a monotherapy or combined with external beam radiation. Low-dose-rate (LDR) brachytherapy involves the permanent implantation of radioactive seeds for continuous emission, while high-dose-rate (HDR) brachytherapy entails the temporary insertion of a high-activity source to deliver potent fractional doses akin to an internal radiation blast.
New Minimally Invasive Alternative Treatments for Prostate Cancer
Cryosurgery
Cryosurgery has emerged as a viable alternative to surgery or radiation for select patients with early-stage prostate adenocarcinoma. The procedure involves the precise placement of cryoprobes into the prostate gland under ultrasound guidance. These probes facilitate the formation of intracellular ice crystals, leading to tumor destruction via freezing temperatures.
High-Intensity Focused Ultrasound (HIFU)
A transrectal probe delivers high-energy ultrasound waves to a targeted region within the prostate, raising temperatures sufficiently to cause coagulative necrosis of malignant cells. These novel techniques offer potential advantages over traditional interventions, including reduced morbidity and improved quality of life. Careful patient selection and counseling regarding risks and benefits are paramount.
Irreversible Electroporation (IRE)
Use of an electrical field created by needles placed into the prostate around the tumor under ultrasound guidance. The treatment produces changes in the wall of the cancer cells leading to cell death.
To refer a patient with a genitourinary cancer or a suspicious tumor finding, please complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.
