Muscle-invasive bladder cancer is the 6th most common cancer in men and 17th most common cancer in women worldwide. The current standard of care includes either radical cystectomy or trans urethral resection of bladder tumor followed by radiotherapy with or without radiosensitizing chemotherapy, also known as organ conserving therapy. No well-powered randomized trials compare these two approaches. BC2001 is the largest organ conservation trial in muscle-invasive bladder cancer, and compares chemoradiotherapy using 5-fluorouracil and mitomycin C vs RT alone. The primary analysis, published in 2012, reported significant improvement in locoregional control with chemoradiotherapy vs radiotherapy alone (HR 0.68 (0.48-0.96); p=0.03) with a median follow-up of five years. Now with 10-year median follow-up, improvement in locoregional control with chemoradiotherapy persists (HR 0.61 (0.43-0.86); p=0.004). As in the primary analysis, disease-related outcomes (disease-free survival, bladder cancer-specific survival, and overall survival) trended toward but did not reach statistical significance.

Given the absence of randomized data comparing radical cystectomy to organ conserving therapy, this further follow-up maintains the centrality of multimodal treatment to practitioners of bladder-conserving therapy but is unlikely to change practices in those who assert that radical cystectomy is the gold-standard for locally invasive bladder cancer despite patients’ continued reluctance to accept randomization to bladder-sparing or radical cystectomy-based approaches, likely making any randomized comparison out of reach. 

(Open Access)

Reference (Pub-Med Link): Hall, E., Hussain, S. A., Porta, N., et al. (2022). Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. European Urology, 82(3), 273–279. https://doi.org/10.1016/j.eururo.2022.04.017

Key Institution: The Institute of Cancer Research, London, UK
Keywords: Bladder

Mycosis fungoides is a chronic condition that warrants novel treatments that minimize long term side effects. Current standard of care includes radiotherapy or topical chemotherapy. This study looks at the efficacy and safety of topical hypericin ointment for early-stage mycosis fungoides in a large multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial. This study included 169 patients. Each cycle of topical hypericin is given twice a week followed by light treatment. They found a statistically significant clinical response with the hypericin ointment, including a 49% index lesion response rate (ILRR) after 3 cycles of hypericin. They did not find any serious adverse reactions. Further research is warranted to establish this treatment as a treatment option for early-stage mycosis fungoides.

(Open Access)

Reference (Pub-Med Link): Kim, E. J., Mangold, A. R., DeSimone, J. A. et al. (2022). Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. JAMA Dermatology, 158(9), 1031–1039. https://doi.org/10.1001/jamadermatol.2022.2749

Key Institution: Perelman School of Medicine at University of Pennsylvania, Philadelphia
Keywords: FLASH, Lymphoma

A phase 2 study of neoadjuvant PD-1 immunotherapy using dostarlimab was conducted in 12 patients with stage II-III rectal adenocarcinoma patients with mismatch repair deficiency. Though the study protocol called for dostarlimab q3 weeks for 6 months followed by chemoRT and surgery, after 6 months of follow up upon completion of dostarlimab therapy, all 12 patients were found to have clinical complete response on MRI, FDG PET, DRE, biopsy, or endoscopy, and no patients at the time of this article’s publication (6-25 months of follow up) have received chemoRT or surgery. This could represent a truly groundbreaking paradigm shift in the management of colorectal cancer for patients with lynch syndrome, and warrants further follow up.

Reference (Pub-Med Link): Cercek, A., Lumish, M., Sinopoli, J., et al. (2022). PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. The New England Journal of Medicine, 386(25), 2363–2376. https://doi.org/10.1056/NEJMoa2201445

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

Anal cancer is more common in people with HIV than the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment and screening for cervical HSIL has led to a decrease in cervical cancer. However, little is known about the treatment of anal HSIL to prevent anal cancer. This article is the largest prospective phase 3 trial investigating how screening and treatment of HSIL can help prevent anal cell cancer development. Patients who were at least 35, HIV+, and had biopsy proven HSIL were either enrolled into active monitoring or an ablative procedure in 1:1 ratio. Of the 4459 patients who underwent randomization 4446 were analyzed with a median follow up of 25.8 months. In the treatment group, 9 cases of anal cancer were diagnosed. In the active monitoring group, 21 cases of anal cancer were diagnosed. The rate of progression to anal cancer was significantly lower in the treatment group than in the active monitoring group (Log-rank p-value: 0.03). Thus, for patients who are found to have biopsy proven anal HSIL, they should be treated with ablative therapy.

Reference (Pub-Med Link): Palefsky, J. M., Lee, J. Y., Jay, N., et al. (2022). Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. The New England Journal of Medicine, 386(24), 2273–2282. https://doi.org/10.1056/NEJMoa2201048

Key Institution: United States

Keywords: Anal Cancer