Apr 23, 2013
The 2013 Genitourinary Cancers Symposium was held February 14-16, in Orlando, Florida, with a record number in attendance—2,350. The following highlights are courtesy of the Genitourinary Cancers Symposium Daily News team.
Attendees learned of two valuable strides in prostate cancer treatment that dramatically improve oncologic outcomes while preserving patient quality of life.
Expanding on the results of COU-AA-301, which led to the approval of abiraterone for use after chemotherapy, the randomized, placebo-controlled phase III COU-AA-302 trial (Abstract 5) favored the abiraterone-containing arm for all primary and secondary endpoint outcomes. Moreover, the safety profile of abiraterone remained favorable with long-term treatment exposure, and no new safety signals emerged with use of either abiraterone or prednisone beyond two years.
The second notable study presented results of the randomized phase III Prostate Cancer Study IV trial that suggested that the period of androgen blockade following radiation therapy for localized high-risk prostate cancer can be safely reduced from 36 months—the current, somewhat-arbitrary standard—to 18 months—what may well become the new standard—without compromising efficacy outcomes (Abstract 3).
- In the largest cohort of patients with prostate cancer undergoing active surveillance, 31.3% of patients had an upgrade in Gleason pathology grade following rebiopsy over a median follow-up of 6.4 years (Abstract 1). The proportion of patients upgraded increased with time at a rate of approximately 1.0% per year. Factors associated with upgrading included the clinical stage at diagnosis, a prostate-specific antigen (PSA) velocity exceeding 2, the percentage of involved prostate biopsy cores at diagnosis, and the time to rebiopsy.
- Ten-year results of the German ARO 96-02 study showed that adjuvant radiation therapy following R0 or R1 resection in patients with pT3 prostate cancer cuts the risk of biochemical progression by approximately 50% as compared with a wait-and-see approach (Abstract 4).
- Researchers discovered that inherited genetic differences at single base-pair locations in inflammation-associated genes may be connected
- ARN-509, a second-generation anti-androgen, yielded impressive preliminary activity in a phase II study of 47 patients with high-risk nonmetastatic CRPC, while also proving to be safe and well tolerated (Abstract 7).
- The addition of dasatinib to docetaxel/prednisone in patients with mCRPC failed to improve overall survival and other efficacy outcomes compared with docetaxel/prednisone alone in the phase III READY trial, although a modest delay in skeletal-related events was observed (Abstract LBA8).
- The VEGF inhibitor, aflibercept, failed to improve overall survival when added to docetaxel/prednisone in mCRPC in the phase III VENICE trial (Abstract 13).
Urothelial carcinoma and urethral, penile, and testicular cancers
Researchers are beginning to harness gene expression information to identify prognostic and predictive biomarkers in urothelial cancer to better identify who stands to benefit from therapy and which therapies might work best in select patients.
Findings from the randomized phase III AUO-AB22/00 trial—the latest attempt to establish the benefit of adjuvant chemotherapy over deferred chemotherapy at the time of progression in locally advanced bladder cancer—turned up negative given that the primary endpoint was not met (Abstract 250). However, as in other adjuvant trials before it, strong signals favoring adjuvant treatment emerged in the German study for progression-free survival, cancer-specific survival, and overall survival; statistical significance was not met.
“I still want to point out that in patients [with lymph node-positive disease], the median progression-free survival was 10 months longer and the median cancer-specific survival was 33 months longer in the adjuvant gemcitabine arm,” noted lead investigator Jan Lehmann, MD, of Saarland University in Germany. Interestingly, these benefits were lost upon the cessation of adjuvant therapy.
Other noteworthy research:
- Because of lack of a reasonable control arm, there has been difficulty in recruiting patients with bladder cancer for whom the Bacillus Calmette-Guerin (BCG) therapy failed to clinical trials of new intravesical therapies. To overcome this problem, researchers at the University of Texas MD Anderson Cancer Center proposed a new fluorescent in situ hybridization (FISH)-based definition of BCG failure (Abstract 246). They determined that patients with cytogenetic abnormalities observed after six weeks of BCG have a 46% chance of recurrence and a 30% chance of progression, thus potentially influencing trial design and negating ethical concerns regarding “standard treatment.”
- The largest study to date to analyzing clinical staging and survival in patients with bladder cancer undergoing radical cystectomy provides strong evidence that current clinical staging is flawed based on a high rate of clinical-pathologic stage discrepancy (Abstract 248). Among the nearly 7,300-patient cohort, a striking 42% were upstaged followed surgery, and upstaging correlated with increased mortality (hazard ratio: 1.90, p < 0.001).
- The key to determining whether men with stage I nonseminomatous germ cell tumors should undergo surveillance or receive adjuvant chemotherapy following orchidectomy may be as simple as measuring CXCL12 expression levels in the excised tissue (Abstract 319). When the CXCL12 expression level was combined with the presence or absence of vascular invasion, a very clear pattern of relapse emerged.
Renal cell cancer
A large retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 to 2007 for more than 8,300 patients with kidney tumors measuring less than 4 cm in diameter finds that not only is active surveillance of small kidney masses on the rise, but it also may actually mitigate the risk of cardiovascular events and death in select patients (Abstract 343).
Although the positive results for active surveillance lend credence to the growing adoption of this strategy over the past decade, lead study investigator William C. Huang, MD, of New York University School of Medicine, urged caution. “Until we are able to adequately predict which tumors will go on to progress and metastasize, we are still taking a risk by observing these tumors,” he told The Daily News. “Nonetheless, this strongly supports the notion that patients who cannot tolerate anesthesia or who have a limited life expectancy are unlikely to benefit from treatment and may potentially have an acceleration in the development of cardiovascular events or even mortality, particularly if treated with radical nephrectomy.”
Additional key findings in renal cell cancer (RCC) included research on first-line treatment of metastatic RCC (Abstract LBA348); targeted-therapy combinations (Abstract 345); mTOR inhibitors versus control therapies (Abstract 347); and personalized immunotherapy (Abstract 357).
Access complete Genitourinary Cancers Symposium Daily News coverage online.