Advanced Prostate Cancer

(UroToday.com) The 2024 South Central AUA annual meeting included a session on lower genitourinary tract cancer, featuring a presentation by Anish Patel discussing 90-day urologic complications from pelvic exenteration at a single, tertiary-level medical center. The management of locally advanced and/or recurrent pelvic malignancies has evolved significantly over the years with improvements in neoadjuvant treatments and perioperative patient care.

(UroToday.com) The 2024 South Central AUA annual meeting included an endourology session, featuring a presentation by Dr. Jeffrey Cadeddu discussing multiparametric MRI in the evaluation of small renal masses. Secondary to cross-sectional imaging, there has been a significant increase in the incidental identification of small renal masses.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on lower genitourinary tract cancer, featuring a presentation by Dr. Peter Sullivan discussing financial toxicity in testicular cancer treatment.  As our understanding of the long-term toxicities of chemotherapy evolves, the landscape for the management of testicular cancer is changing. Studies such as the SEMS¹ and PRIMETEST² trials are examining the utilization of Retroperitoneal lymph node dissection (RPLND) as the primary therapy for lower stage metastatic testicular cancer.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on lower genitourinary tract cancer, featuring a presentation by Clare Weiland discussing whether the use of continuous bladder irrigation after trans urethral resection of bladder tumor (TURBT) increases the risk of complications.  In the United States, bladder cancer is the fourth most common malignancy and eighth most common cancer risk deaths among men. The diagnosis and treatment of bladder cancer involves a TURBT, with hemostasis usually confirmed in the operating room.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on prostate cancer, featuring a presentation by Dr. Gal Saffati discussing a systematic review regarding whether veterans should be classified as high risk for prostate cancer screening. Prostate cancer is a major concern as the most common non-skin cancer among U.S. males.

(UroToday.com) The 2024 South Central AUA annual meeting included the fellow essay podium presentation competition, featuring a presentation by Dr. Jorge Alcacio-Mendoza discussing whether PSMA PET SUV_max can predict high risk pathology and high risk disease. PSMA/PET is the most useful method for staging, given its ability to detect more lesions at lower PSAs, compared to other current imaging modalities. However, its ability to predict adverse pathologic features has not been thoroughly investigated.

(UroToday.com) The 2024 South Central AUA annual meeting included the Sushil Lacy manuscript competition, featuring a presentation by Dr. Amanda Myers discussing the elucidation of response rates to additional BCG and implications for clinical trial design. Intravesical BCG remains the most effective treatment for high-grade nonmuscle invasive bladder cancer (NMIBC), so much so that clinical trials are designed around ‘categories’ of recurrences after BCG.

(UroToday.com) The 2024 South Central AUA annual meeting included the resident essay podium presentation competition, featuring a presentation by Dr. Carlos Gonzalez-Martinez discussing whether we can predict locally advanced disease features with PSMA PET by correlating molecular imaging TNM with pathological TNM in radical prostatectomy specimens. PSMA PET with any available agent is one of the most useful and innovative staging methods for prostate cancer.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Amanda Myers discussing a contemporary US claims analysis assessing real-world treatments following BCG induction in patients with non muscle invasive bladder cancer (NMIBC). Intravesical BCG is the guideline-recommended first-line treatment for high-risk NMIBC, including for CIS. However, a substantial number of patients experience treatment failure with BCG. Notably, there has been a recent surge in clinical trials focused on patients who have recurrent disease of their NMIBC after BCG. Due to ongoing BCG shortages and access to alternative agents, the true number of patients who are receiving BCG induction is unclear. At the 2024 South Central AUA annual meeting, Dr. Myers and colleagues presented results evaluating this question and elucidated alternative treatment agents that patients received from a contemporary US insurance claims database.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Amanda Myers discussing urothelial carcinoma of the prostate and intravesical therapy. High-grade prostatic urethral involvement in patients with non-muscle invasive bladder cancer (NMIBC) is classified as high-risk according to the AUA guidelines, although the best treatment approach is not well-established. Limited evidence exists for bladder-sparing treatments in these patients. At the 2024 South Central AUA annual meeting, Dr. Myers and colleagues reported results on the outcomes of patients with high-grade prostatic urethral involvement treated with bladder-sparing options.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on kidney cancer, featuring a presentation by Dr. Frances Alba discussing nephron sparing surgery for localized renal masses. Dr. Alba started by emphasizing that a partial nephrectomy for small renal masses is associated with excellent oncologic outcomes and excellent renal function outcomes.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Gal Saffati discussing a systematic review and meta-analysis of early adjuvant chemotherapy in muscle invasive bladder cancer. Muscle invasive bladder cancer necessitates a comprehensive treatment approach, typically commencing with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection. The efficacy of neoadjuvant chemotherapy in muscle invasive bladder cancer patients has been substantiated through randomized clinical trials, demonstrating improved median overall survival and enhanced pathological downstaging when compared to surgery alone.¹ However, there are scenarios where upfront cystectomy and adjuvant chemotherapy may be considered. Dr. Saffati and colleagues sought to evaluate whether earlier administration of adjuvant chemotherapy can significantly augment survival rates in this specific patient population.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Yair Lotan discussing 36-month follow-up from a phase 3 trial assessing the efficacy of intravesical nadofaragene firadenovec for patients with BCG-unresponsive non muscle invasive bladder cancer (NMIBC).

(UroToday.com) The 2024 South Central AUA annual meeting included a session on kidney cancer, featuring a case discussion on the management of localized renal masses in younger patients and patients with heritable kidney cancer syndromes moderated by Dr. Woodson Smelser hosting urology panelists Drs. Zeynep Gul, Marcelo Bigarella, and Jonathan Heinlen.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Carlos Riveros discussing a systematic review and meta-analysis of randomized clinical trials assessing adjuvant immunotherapy in high-risk muscle invasive urothelial carcinoma. Approximately 50% of patients with muscle invasive urothelial carcinoma develop recurrence following radical surgery.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Ali Nasrallah discussing the BRAVO study assessing white versus blue light cystoscopy in non muscle invasive bladder cancer (NMIBC) among veterans in an equal access setting. Bladder cancer is the 6^th most common cancer in the United States, with 83,190 new cases expected in 2024. Recent studies have shown conflicting evidence regarding the utility and impact of blue light cystoscopy on oncologic outcomes such as recurrence.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Gal Saffati discussing exposures and bladder cancer risk among military veterans. Bladder cancer is a significant concern among veterans, with approximately 3,200 U.S. veterans diagnosed annually, making it the fourth most diagnosed cancer within the Veterans Affairs (VA) system.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on kidney cancer, featuring a presentation by Dr. Kelly Bree discussing indications and outcomes for ablation therapy in renal masses. Dr. Bree notes that each of the AUA, EAU, and NCCN make statements in their guidelines regarding ablation of renal masses. The following is supported by the AUA:

• Statement 25: Clinicians should consider thermal ablation as an alternate approach for the management of cT1a solid renal masses <3 cm in size. For patients who elect thermal ablation, a percutaneous technique is preferred over a surgical approach whenever feasible to minimize morbidity. (Moderate Recommendation; Evidence Level: Grade C)
• Statement 26: Both radiofrequency ablation and cryoablation may be offered as options for patients who elect thermal ablation. (Conditional Recommendation; Evidence Level: Grade C)

The following is supported by the EAU:

• Offer active surveillance or tumor ablation to frail and/or comorbid patients with small renal masses (Strength rating: Weak)
• Perform a percutaneous renal mass biopsy prior to, and not concomitantly with, thermal ablation (Strength rating: Strong)
• When thermal ablation or active surveillance are offered, discuss with patients about the harms/benefits with regards to oncological outcomes and complications (Strength rating: Strong)
• Do not routinely offer thermal ablation for tumors > 3cm and cryoablation for tumors > 4 cm (Strength rating: Weak)

The following is supported by the NCCN guidelines:
 
Ablation is an ideal treatment option for small renal masses in (i) patients who are unfit or refuse surgery, (ii) patients with a prior ipsilateral partial nephrectomy, (iii) those with limited reserve (severe CKD, solitary kidney), (iv) those with genetic predisposition syndromes (ie. von Hippel Lindau). Outcomes of ablation are excellent, with 5 year cancer specific survival rates of ~95% for cT1a tumors. Thus, survival is often not dependent on partial nephrectomy versus radiotherapy versus ablation, but on comorbidities and competing risks of mortality.

There is currently no level 1 evidence comparing modalities, with previous studies having failed to reach accrual targets (ie. SURAB, CONSERVE). The recent NEST trial demonstrated feasibility of recruiting to a cohort-embedded randomized clinical trial comparing cryoablation versus partial nephrectomy:¹

For the remainder of the presentation, Dr. Bree discussed the specific ablative techniques: cryoablation, radiofrequency ablation, and microwave ablation. Starting with cryoablation, Dr. Bree discussed a study from Breen et al. [2] assessing 3- and 5-year outcomes of cryoablation in 220 patients with biopsy-proven RCC. Local recurrence free survival was 93.9% (all recurrences successfully treated with repeat ablation), metastasis free survival was 94.4%, and the major complication rate (Clavien-Dindo 3+) of 4.9%.

In a recent systematic review and meta-analysis performed by Gao et al.,³ they compared the efficacy of cryoablation versus robot-assisted partial nephrectomy in the treatment of cT1 renal tumors. This study included a total of 10 studies comprising 2,011 patients. Compared to robotic partial nephrectomy, the cryoablation group had a shorter hospital stay, less blood loss, and fewer overall complications, but a higher recurrence rate [OR 7.83; 95% CI 4.32 to 14.19; p < 0.00001]. There were no significant differences between the two groups in terms of operative time, minor complications (Clavien-Dindo Grade 1-2), major complications (Clavien-Dindo Grade 3-5), changes in renal function at 12 months post-operation, recurrence-free survival, and overall survival:
Discussing radiofrequency ablation, Dr. Bree highlighted a study from Abdelsalam et al.⁴ assessing the 20-year outcomes of radiofrequency ablation for solitary T1a RCC. Among 243 patients, the median tumor size was 2.5 cm, and the median follow-up was 44 months. The local recurrence free survival rate was 96.5% (ablation zone recurrences treated with ablation n = 3; partial nephrectomy n = 3; active surveillance n = 1; median time to detection: 8.5 months), metastasis free survival rate was 100%, and major complication rate (Clavien-Dindo 3+) of 4.1%. Rates of recurrence after radiofrequency ablation are higher than partial nephrectomy, however, cancer specific survival remains excellent:

Dr. Bree also noted that as a tumor increases in size by 1 cm, the likelihood of residual tumor is 2.19 times higher (95% CI 1.74 – 2.76). Moreover, cryoablation is associated with increased risk of bleeding compared to radiofrequency ablation, with the likelihood increasing with tumor size, central location, and the number of probes used. Microwave therapy is newer and less commonly used than cryoablation or radiofrequency ablation. In a small study of 26 patients, with a mean tumor size of 2.3 cm, and a median follow-up of 19.1 months, local recurrence free survival was 100%, cancer specific survival rate was 94%, and major complication rate (Clavien Dindo 3+) was high at 11.5% (included one death from complications following retroperitoneal hemorrhage, with other complications secondary to complications from bleeding after resuming anticoagulation).

At MD Anderson Cancer Center, Dr. Bree and colleagues follow the algorithm below for deciding on ablation approach:
Previous work from Andrews et al.⁵ assessing 1,422 patients with cT1a renal tumors demonstrates that 5-year local recurrence is rare: 97.7% for partial nephrectomy, 95.9% for radiofrequency ablation, 95.9% for cryoablation:
Additionally, 5-year cancer specific survival were the same in those treated with surgery versus ablation: 99.3% for partial nephrectomy, 95.6% for radiofrequency ablation, and 100% for cryoablation:

Dr. Bree concluded her presentation discussing indications and outcomes for ablation therapy in renal masses with the following take-home points:

• Ablation is a useful tool for the treatment of small renal masses: it avoids a major operation in those patients with comorbidities or a complex surgical history
• Local recurrence is rare, and when needed salvage treatment is often feasible with repeat ablation or surgery
• High grade complications are infrequent and can generally be managed without surgical intervention
• Cancer specific survival is excellent

Presented by: Kelly Bree, MD, Urologist, The University of Texas MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 South Central American Urological Association (AUA) Annual Meeting, Colorado Springs, CO, Wed, Oct 30 – Sat, Nov 2, 2024.

References:

1. Neves JB, Warren H, Santiapillai J, et al. Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomized Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy. Eur Urol. 2024 Apr;85(4):333-336.
2. Breen DJ, King AJ, Patel N, et al. Image-guided cryoablation for sporadic renal cell carcinoma: Three- and 5-year outcomes in 220 patients with biopsy-proven renal cell carcinoma. Radiology. 2018 Nov;289:554-561.
3. Gao HY, Zhou L, Zhang JB, et al. Comparative efficacy of cryoablation versus robot-assisted partial nephrectomy in the treatment of cT1 renal tumors: A systematic review and meta-analysis. BMC Cancer. 2024 Sep 16;24(1):1150.
4. Abdelsalam M, Awad A, Baiomy A, et al. Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience. Cancers (Basel). 2023 Jan 31;15(3):909.
5. Andrews JR, Atwell T, Schmit G, et al. Oncologic outcomes following partial nephrectomy and percutaneous ablation for cT1 renal masses. Eur Urol. 2019 Aug;76(2):244-251.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on kidney cancer, featuring a presentation by Dr. Tyler Robin discussing indications and outcomes for radiation therapy in renal masses. Dr. Robin started his presentation by highlighting the current state of the data for stereotactic ablative radiotherapy for primary renal cell carcinoma.

(UroToday.com) The 2024 South Central AUA annual meeting included a session on bladder cancer, featuring a presentation by Dr. Chad LaGrange discussing the case for radical cystectomy as treatment for high risk non muscle invasive bladder cancer (NMIBC). According to the AUA guidelines, high grade urothelial carcinoma has the following features: