Outcomes in surgically resectable oropharynx cancer treated with transoral robotic surgery versus definitive chemoradiation.

PURPOSE: Optimal treatment strategies for the management of oropharyngeal squamous cell carcinoma (OPSCC) remain unclear. The objective of this study is to examine the role of transoral robotic surgery (TORS) on functional and treatment outcomes. MATERIALS AND METHODS: A retrospective review of patients with OPSCC (tonsil/base of tongue) who underwent TORS with neck dissection± adjuvant therapy between January 2011 to December 2016 were compared to a stage matched cohort of patients treated with primary chemoradiation. Demographic, treatment, and outcome data were collected. RESULTS: 54 patients received primary chemoradiation and 65 patients (surgical group) received TORS ± adjuvant therapy for clinically staged disease meeting study criteria. 25% (N = 17) were treated with surgery alone. The remainder of the surgical group received postoperative radiation (N = 48), half of which received adjuvant chemotherapy (N = 24) in addition to radiation. 63% (N = 41) of the patients did not have risk factors for chemotherapy. No differences in overall or disease free survival were observed with TORS compared to chemoradiation (p = 0.9), although Charlson Comorbidity Index (CCI) was higher in the surgical group (p = 0.01). The strongest predictor of prolonged gastrostomy tube use was not treatment, but rather co-morbidity (p = 0.03), with no significant differences beyond 12 months. CONCLUSION: Although no significant survival differences were observed across treatment groups, this was maintained despite increased comorbidity index in the surgical patients. Given the ability to de-escalate and/or eliminate adjuvant therapy, particularly in a less healthy population, TORS would appear to be the viable treatment option it has become.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.

BACKGROUND: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. CONCLUSIONS: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.

HP1γ expression is elevated in prostate cancer and is superior to Gleason score as a predictor of biochemical recurrence after radical prostatectomy.

BACKGROUND: Aberrant chromatin structure in cancer cells results from altered proteins involved in its packaging. Heterochromatin protein 1 gamma (HP1γ) is a non-histone heterochromatic protein that functions to maintain chromatin stability and is important in embryonic development. Given an interest in the role developmental genes play in cancer, we investigated HP1γ expression in prostate cancer (PCa) and its prognostic associations. METHODS: Tissue microarrays consisting of benign (N = 96), localized cancer (N = 146), metastatic PCa (N = 44), and HGPIN (N = 50) were immunoflourescently stained for HP1γ and Ki-67. Using a novel, automated quantitative imaging system, VECTRA™, epithelial staining in both the nucleus and cytoplasm was quantified and compared against clinicopathologic variables. RESULTS: HP1γ is significantly elevated in HGPIN (80%), localized PCa (76%), and metastatic PCa (98%) compared to benign tissues from both the nuclear and cytoplasmic compartments (P < 0.0001). Increased nuclear and total HP1γ expression was associated with Gleason score (P = 0.02 and P = 0.04 respectively). Given known binding to the C-terminus of Ki-67, a co-expression analysis was performed that revealed a correlation between nuclear and cytoplasmic HP1γ and Ki-67 (Pearson Coefficient 0.321 and 0.562 respectively, P < 0.0001). Cox survival analysis demonstrated that cytoplasmic HP1γ expression was an independent prognostic marker and out-performed pathological Gleason score for predicting PSA-recurrence after radical prostatectomy. CONCLUSIONS: In this first detailed analysis of HP1γ expression in cancer, VECTRA™ demonstrates compartmentalized and total HP1γ protein expression is increased in PCa and that expression correlates with clinical outcomes better than Gleason score. Given the critical role HP1γ plays in chromatin organization and gene expression, it represents a novel prognostic and therapeutic target.

Treatment trends in oropharyngeal carcinoma: Surgical technology meets the epidemic.

OBJECTIVE: To characterize temporal trends in treatment patterns for oropharyngeal carcinoma, and to evaluate the emerging role of surgical therapy in the era of transoral robotic surgery (TORS). METHODS: Patients with oropharynx cancer between 2004 and 2016 identified using the National Cancer Database. Demographics and primary treatment modalities were obtained. Treatment was classified as surgery alone, surgery with radiation/chemotherapy, or primary radiation/chemotherapy. Annual distribution of cases treated by the various modalities was tabulated by site and early (I/II) versus late (III/IV) stage disease (AJCC 7th edition). The "TORS era" was defined as beginning in 2010. RESULTS: 149,534 patients were identified. The majority (56.8%) were treated with radiation ± chemotherapy. 53,069 patients had surgery as part of treatment, 72.6% (N = 38,533) of which received adjuvant therapy. 5293 TORS procedures were performed between 2010 and 2016 with trends away from open and other endoscopic procedures. Despite a 31.0% increase in the number of cases treated surgically from before TORS (2009) to 2016, the percentage of cases treated surgically decreased from 35.0% to 32.7%, with a 44.2% increase in non-surgical therapy. Increases in the percentage of patients treated surgically were observed for base of tongue tumors (24.3-25.2%) and early stage disease (59.9-62.2%). CONCLUSION: Despite the increase in the overall number of patients with oropharynx cancer, the percentages of patients treated surgically remains relatively stable. Notable increases were observed for base of tongue tumors and early stage disease.