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Guideline Updates

NCCN Updates Clinical Practice Guideline for Bladder Cancer

March 10, 2021

On March 9, 2021, the National Comprehensive Cancer Network (NCCN) released an update to its clinical practice guideline for bladder cancer.

Under initial evaluation, a bullet was revised to “Office cystoscopy, enhanced if available.” Under primary evaluation/surgical treatment, “If sessile, suspicious for high grade or Tis: Consider selected mapping biopsies” was removed.

The algorithms for non-muscle invasive bladder cancer were extensively revised to provide recommendations for management based on AUA risk stratification group.

In the section now labeled “Management of Positive Urine Cytology,” two bullets were added under evaluation stating, “if initial positive cytology, consider repeating cytology test within 3 months,” and “If repeated positive cytology,” with sub-bullets underneath listing the current recommendations for this bullet.

Under additional workup for stage II muscle invasive bladder cancer, a bullet was added, “Estimate GFR to assess eligibility for cisplatin.” Under primary treatment, “bladder preservation with concurrent chemoradiotherapy (category 1),” was added. Additionally, the reassessment bullet was revised to “reassess tumor status 2-3 months after treatment completion.”

Adjuvant treatment for cystectomy candidates with stage II muscle invasive bladder cancer was updated to “adjuvant cisplatin-based chemotherapy if no neoadjuvant treatment,” or “adjuvant RT (pT3-4, or positive nodes/margins (category 2B),” based on pathologic risk.

“± intravesical therapy” was added to TURBT under adjuvant treatment for non-cystectomy candidates with stage II muscle-invasive bladder cancer and a tumor 2-3 months after primary treatment completion.

For stage IVA muscle invasive bladder cancer and M1a disease, the CR options was revised from “concurrent chemoradiotherapy or cystectomy” to “consider consolidative local therapy in selected cases.”

In the section labeled principle of imaging for bladder/urothelial cancer, under staging for abdominal and pelvic imaging, a bullet was updated to MR urography (MRU) may be appropriate, especially in patients with…” Additionally, a section labeled “Metastatic Disease – Patients Being Observed,” was added. Under staging for urothelial carcinoma of the prostate/primary carcinoma of the urethra, a bullet was revised to “Staging: chest CT (preferred) or PA and lateral chest x-ray.”

In the section labeled principles of surgical management, under TURBT/maximal TURBT for treatment, a bullet was revised to “Maximally complete and safe TURBT is an essential part of bladder preservation.” “Concurrent chemoradiotherapy is generally most suitable for patients with solitary tumors, negative nodes, no extensive or multifocal CIS, no moderate/severe tumor-related hydronephrosis, and good pre-treatment bladder function” was moved to the section labeled principles of radiation management of invasive disease.

Under partial cystectomy, a bullet was revised to “May be used for cT2 muscle invasive disease with solitary lesion in location amendable to segmental resection with adequate margins, particularly for purely non-urothelial histology.” Under radical cystectomy/cystoprostatectomy, a bullet was revised to “in non-muscle invasive disease, radical cystectomy is generally reserved for residual high-grade cT1, variant histology, lymphovascular invasion, concomitant CIS, and Bacillus Calmette-Guérin (BCG)-unresponsive disease,” and “In appropriately selected female patients, approaches that preserve the uterus, vagina, and/or ovaries should be employed when feasible” was added.

Under radical nephroureterectomy with cuff or bladder, a bullet was revised to “neoadjuvant chemotherapy should be considered in select patients with high-grade disease or concerning radiographic findings” and “adjuvant chemotherapy may also be considered in patients who did not receive neoadjuvant chemotherapy” was added.

Under urethrectomy, a bullet was updated to “with T2 primary carcinoma of the urethra may be treated with urethrectomy and cystectomy with organ-sparing approached when feasible in appropriately selected cases.” Under endoscopic management of upper tract urothelial cancer, a bullet “hereditary predisposition (eg, hereditary nonpolyposis colon cancer [HNPCC])” was removed.

In the section labeled principles of pathology management, an entire section, “Melanocytic tumors – Malignant melanoma, Naevus, Melanosis,” was removed, and malignant melanoma was added to miscellaneous tumors. The mesenchymal tumors section was revised to include malignant inflammatory myofibroblastic tumor, malignant perivascular epithelioid cell tumor, and malignant solitary fibrous tumor.

In the section labeled principles of intravesical treatment, under induction intravesical chemotherapy or BCG, other options were updated to include sequential gemcitabine/docetaxel, epirubicin, valrubicin, docetaxel, or sequential gemcitabine/mitomycin. Under intrapelvic or intravesical therapy for upper tract tumors, a bullet for primary therapy was revised to “perioperative intravesical chemotherapy with mitomycin or gemcitabine should be considered following nephroureterectomy with cuff of bladder resection.”

In the section labeled principles of systemic therapy, a bullet was added recommending that adjuvant therapy should be considered is neoadjuvant was no given for UTUC. A bullet was revised to “carboplatin should not be substituted for cisplatin in the perioperative bladder cancer setting.”

Avelumab maintenance was clarified as a category 1 recommendation for first-line systemic therapy for locally advanced or metastatic disease (stage IV). Durvalumab was removed as an alternative preferred regimen for second-line systemic therapy based on FDA withdrawal of the indication.

Under preferred regimens for subsequent-line systemic therapy for locally advanced or metastatic disease, enfortumab vedotin was changed from a category 2A to a category 1 recommendation.

In the section labeled principles of radiation management of invasive disease, a bullet was revised to “concurrent chemoradiotherapy (preferred) or RT alone should be considered as potentially curative therapy for medically inoperable patients. Concurrent chemoradiotherapy or RT alone should be considered for local palliation in patients with metastatic disease.”

For upper GU tract tumors in the renal pelvis, workup was updated to include “or CT” with chest x-ray. For adjuvant treatment for renal pelvis and urothelial carcinoma of the ureter in patients with pathologic staging pT2, pT3, pT4, and pN+, “± RT” was added to “consider adjuvant chemotherapy.”

Lastly, primary carcinoma of the urethra, primary treatment for cN0 lymph nodes was revised to include “surgery alone for non-urothelial histology,” as the last option.—Janelle Bradley

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