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AGA guideline on surveillance for hepatobiliary cancers in primary sclerosing cholangitis

The American Gastroenterological Association (AGA) has published updated practice guidelines on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis (PSC) [1]. In patients >=20 years of age at any PSC disease stage, the guidelines support surveillance every 6 to 12 months with abdominal imaging (ultrasound, abdominal computed tomography scan, or magnetic resonance imaging/magnetic resonance cholangiopancreatography); serum levels of cancer antigen (CA) 19-9 are optional. They caution against routine endoscopic retrograde cholangiopancreatography for surveillance, but support its use in evaluating patients with worsening clinical symptoms, cholestasis, a dominant stricture, or increasing CA19-9 levels. Our recommendations are consistent with these guidelines.

 

Increasing incidence and mortality of anal cancer

Although still relatively uncommon, the incidence of anal squamous cell cancer (SCC) is increasing in the United States (US) and elsewhere. According to the US Cancer Statistic dataset, incidence rates for anal SCC increased from 2001 to 2015 by 2.7 percent per year, with the most pronounced increases in women between the ages of 60 and 69 and in young black men [2]. Mortality related to anal cancer and the number of patients presenting with distant or regional (nodal) disease also increased during this time period. Anal SCC is one of the fastest accelerating causes of cancer incidence and mortality in the US, and may surpass cervical cancer to become the leading human papillomavirus-linked cancer in older women.

 

Secondary cytoreduction versus chemotherapy alone for recurrent ovarian cancer

In patients with platinum-sensitive recurrent ovarian cancer, observational studies have suggested a survival advantage with secondary cytoreduction over chemotherapy alone, but are limited by likely selection bias. Now, in a randomized trial (Gynecologic Oncology Group 213) including nearly 500 patients with a complete response to front-line chemotherapy and a recurrence after at least six months, cytoreduction plus adjuvant chemotherapy resulted in a median overall survival of 51 months versus 65 months with chemotherapy alone, a difference that was not statistically significant [3]. We continue to reserve secondary cytoreduction for patients with ovarian cancer that recurred at least six months after platinum-based chemotherapy and has a limited number of involved sites, while awaiting results of another randomized trial (DESKTOP III) to further inform our approach.

 

Cabazitaxel as third-line agent for metastatic prostate cancer

Following failure of first-line docetaxel, the optimal sequencing of new agents (abiraterone, enzalutamide, cabazitaxel) for metastatic castration-resistant prostate cancer (CRPC) is unknown. We generally prefer cabazitaxel as the second-line agent, but others may choose either abiraterone or enzalutamide due to adverse effects associated with cabazitaxel. For patients who fail second-line therapy with abiraterone or enzalutamide, however, the phase III CARD trial found that third-line cabazitaxel was superior to the alternative inhibitor (abiraterone or enzalutamide) for overall and progression-free survival as well as biochemical and radiographic response rates [4]. Adverse events grade >=3 occurred in a similar percentage of patients in either group, although some were more frequent with cabazitaxel (asthenia/fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia). These findings confirm that the chance of achieving disease control is low after treatment failure on abiraterone or enzalutamide when the alternative inhibitor is used for third-line therapy, and that cabazitaxel is preferred in this setting, despite its greater toxicity.

 

HPV status and outcomes in nonoropharyngeal SCC of the head and neck

Patients with human papilloma virus (HPV)-positive squamous cell carcinoma (SCC) of the oropharynx have improved prognoses and treatment outcomes relative to those with HPV-negative SCC of the head and neck. However, outcomes for those with HPV-positive SCC involving nonoropharyngeal (non-OP) sites were previously unclear. In an observational study of approximately 25,000 patients with SCC of the head and neck, HPV positivity was associated with improved overall survival for certain non-OP sites, including the hypopharynx, oral cavity, and larynx [5]. Although current treatment regimens for SCC of the head and neck are not determined by HPV status, clinical trials are exploring whether less intensive regimens will be effective for those with HPV-positive disease. While these data suggest a favorable prognosis for patients with HPV-associated head and neck cancer of non-OP sites, further studies are needed before changing treatment practice.

 

1. Bowlus CL, Lim JK, Lindor KD. AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review. Clin Gastroenterol Hepatol 2019; 17:2416.

 

2. Deshmukh AA, Suk R, Shiels MS, et al. Recent trends in squamous cell carcinoma of the anus incidence and mortality in the United States, 2001-2015. J Natl Cancer Inst 2019.

 

3. Coleman RL, Spirtos NM, Enserro D, et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. N Engl J Med 2019; 381:1929.

 

4. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med 2019.

 

5. Tian S, Switchenko JM, Jhaveri J, et al. Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base. Cancer 2019; 125:2782.

 

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