The 2017 Genitourinary Cancers Symposium featured a wide variety of novel and important research across a variety of specific fields. The theme of the meeting was “Translating Research to Value-Based and Patient-Centric Care.” Studies about everything from genomic markers to novel drug combinations focused on the idea of bringing the best possible treatments out of the lab and trial setting and into each patient’s care.
Below are some of the top studies presented at the Symposium, which was led by Program Committee Chair William L. Dahut, MD, of the National Cancer Institute at the National Institutes of Health, and Steering Committee Chair Robert S. DiPaola, MD, of the University of Kentucky.
Molecular Characterizations and Their Impact on Therapy
A number of abstracts focused on improving our understanding of the genetic makeup of several malignancies and how those molecular details may help guide therapy.
Three studies examined some of the genomic underpinnings of prostate cancer:
- A combined analysis of several published genomic analyses of primary and metastatic prostate cancer shed some light on what researchers call the “long tail” of mutated genes in patients with prostate cancer, which refers to mutations that are seen in only 1% to 5% of patients and that may not appear on a single-cohort analysis. The study found 78 significantly mutated genes, 37 of which were not previously reported as significantly mutated genes in prostate cancer, and 23 of which were not previously identified as recurrently altered in any cancer. Novel prostate cancer genes included CUL3 and SPEN, and one novel prostate cancer pathway was SWI/SNF (Abstract 131).
- The Decipher (GenomeDx Biosciences) genomic classifier was able to predict metastasis and prostate cancer–specific mortality from diagnostic biopsy tissue specimens of patients treated with either radical prostatectomy or radiation therapy plus androgen deprivation therapy, according to this study (Abstract 4). Decipher performed better at prediction of metastasis than either the UCSF-CAPRA (University of California, San Francisco, Cancer of the Prostate Risk Assessment) tool or National Comprehensive Cancer Network risk group. It was also a significant predictor of prostate cancer–specific mortality, with a hazard ratio of 1.57 per 10% increase in score (95% CI [1.07, 2.40]; p = 0.02).
- Quantification of full-length androgen receptor (AR-FL) mRNA from circulating tumor cells was prognostic for outcomes in patients who had metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide. Patients who were AR-FL negative had a median progression-free survival (PFS) of 11.1 months compared with 8.7 months in patients who had AR-FL levels less than the median and 3.2 months in those with AR-FL levels greater than the median (p < 0.001). Overall survival times were 33.3 months, 18.0 months, and 11.3 months, respectively (p < 0.001). This suggests that AR-FL quantification could serve as another molecular biomarker in this population (Abstract 132).
The 2017 Genitourinary Cancers Symposium featured a wide variety of novel and important research across a variety of specific fields.
- An analysis of different published methods for molecular subtyping of muscle-invasive bladder cancer found high concordance between those methods and examined how these subtypes differ in terms of response to neoadjuvant cisplatin-based chemotherapy. The luminal subtype had the best prognosis independent of neoadjuvant cisplatin-based chemotherapy, whereas the prognosis of those with basal tumors improved the most after neoadjuvant chemotherapy compared with surgery. Poor survival with claudin-low tumors suggested that this subtype may be resistant to cisplatin-based chemotherapy and could benefit from other therapies (Abstract 281).
Novel Therapies, Settings, and Strategies
Other presentations focused on novel drugs, older regimens in new settings, and other types of treatment beyond medical therapy.
Two studies looked at combinations or therapies already in use but assessed them in new, difficult settings:
- The high-dose chemotherapy regimen of paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide is an option for patients who have relapsed advanced germ cell tumors. A study that enrolled 101 patients tested this regimen with therapeutic drug monitoring for carboplatin to optimize therapy; the complete response rate was 45%, and 70% of patients had a favorable response. The median PFS was 12.3 months in the full cohort but had not yet been reached in those who had a favorable response. The monitoring protocol allowed targeting of the appropriate area under the curve for carboplatin (Abstract 401).
- A phase II study found that atezolizumab plus bevacizumab has promising efficacy compared with sunitinib in a subgroup of patients with metastatic renal cell carcinoma who were positive for PD-L1. The hazard ratio of 0.64 (95% CI [0.38, 1.08]) for PFS favored the combination therapy instead of sunitinib. The median PFS with atezolizumab plus bevacizumab was 14.7 months compared with 7.8 months with sunitinib; safety was similar to earlier studies of these agents. The phase III IMmotion151 trial will continue to evaluate the clinical benefit of this combination compared with sunitinib (Abstract 431).
Two other studies examined some new therapies in difficult malignancies:
- A single-arm, phase II study of 28 patients who had HPV-negative penile squamous cell carcinoma found that the multitargeted tyrosine-kinase inhibitor dacomitinib had promising activity. The objective response rate was 32.1%, and another 46.4% of patients had stable disease; this was among the highest single-agent response rate seen in this malignancy. The 12-month PFS rate was 26.2%, and the 12-month overall survival rate was 54.9%. Skin reactions were the most frequent treatment-related adverse events. The study also found that response seemed independent of EGFR alterations and that downstream effectors of EGFR signaling are worthy of additional investigation (Abstract 399).
- A single-institution study showed that cryoablation—a technology that has improved substantially in recent years—of cT1 solitary renal masses in otherwise healthy patients offered good oncologic control and excellent safety. Among a cohort of 43 patients, only one (2.3%) developed a local recurrence during a median follow-up period of 22 months, and another two patients (4.6%) developed metastatic disease. No one died as a result of renal cell carcinoma during the follow-up period. There is a potential role for repeat ablation after local recurrence, but longer follow-up data are needed to better evaluate this treatment modality (Abstract 433).
And, finally, sometimes the best therapy is avoidance of therapy:
- A study of 52 patients showed that active surveillance was a reasonable treatment option for certain patients with metastatic renal cell carcinoma. Most patients (69%) began the study in the favorable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) class (25%, intermediate; 6%, poor); importantly, there were few changes in IMDC class after surveillance, and only four patients moved from good to intermediate status. After a median follow-up of 38.5 months, the median change in tumor burden after surveillance was 2.2 times, the median time on surveillance was 19.9 months, and the median overall survival was 77.6 months. Only IMDC class at baseline was correlated with time on surveillance. Using active surveillance in selected patients could delay systemic treatment (Abstract 435).
Save the date for the 2018 Genitourinary Cancers Symposium, to be held February 8-10, in San Francisco.