Update on Kidney Cancer and AUA Guidelines

Educational Objectives

The goal of this program is to improve the treatment of patients with kidney cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Summarize the recommended treatment for patients with T1a renal masses.
2. Optimize the use of ablation and active surveillance in patients with renal masses.
3. Evaluate the efficacy of immunotherapy and adjuvant therapy in the treatment of patients with kidney cancer.

Summary

Kidney cancer: represents ≈3% of all cancers; majority of tumors curable with surgery (incidence of metastases at time of diagnosis ≈20%); risk for distant recurrence following curative resection ≈5%

Diagnosis: some kidney cancers have characteristic signs on imaging studies (biopsy may not be required before surgery); characteristics of others not obvious on ultrasonography or computed tomography (eg, complex cyst); Bosniak classification — categorizes renal cysts; in Bosniak class I and II cysts, risk for malignancy negligible; Bosniak II defined as cyst with single septation (treatment not required); Bosniak IIF cyst characterized by slight irregularity of septation (risk for malignancy 5%); management with active surveillance safe; repeat imaging at 6 mo and 1 yr recommended; Bosniak III cyst characterized by thickened or calcified septation (risk for malignancy 50%); resection recommended in healthy patients; Bosniak IV lesion mostly solid (incidence of cancer ≈100%)

Surgical management: resection traditionally performed using open technique; associated with severe postoperative pain due to incision through multiple layers of muscle; majority of resections now performed laparoscopically or robotically; patients usually discharged 1 day after surgery; recovery time much shorter than with open technique; outcomes for laparoscopic and robotic techniques equivalent

American Urological Association guidelines: T1a masses (<4 cm) — when intervention indicated, partial nephrectomy minimizes risk for chronic kidney disease or progression of kidney disease; more appropriate than total nephrectomy; associated with favorable oncologic outcomes (eg, excellent control of local disease); in 2005, standard of care at speaker’s institution radical nephrectomy; since 2009, majority of resections accomplished by partial nephrectomy (laparoscopic or robotic); prohibitively large tumor only indication for open resection; thermal ablation should be considered as alternative approach in T1a masses <3 cm; usually performed percutaneously using radio frequency ablation; inform patients that risk for persistence of recurrence of tumor increased (10%-14%); Bosniak III to IV cysts — for cysts <2 cm, management with active surveillance appropriate (even in healthy patients); new guideline recognizes that risk for metastases from cysts <3 cm minimal (observation previously recommended only in poor surgical candidates)

Overview of treatment: previously, systemic agents for treatment of kidney cancer limited to interferon and interleukin-2 (rates of response <10%); many small molecules that target receptors now available

VHL gene: regulates pathway that senses hypoxia, promotes formation of blood vessels, buffers acidic pH, and increases uptake of glucose; kidney cancer characterized by dysfunction of VHL gene and activation of pathway even in absence of hypoxia; understanding pathway has led to development of many drugs that target receptors; angiogenesis primary target

Biomarkers: goal ability to predict clinical response to antineoplastic agents; dramatic reduction in cost of genomic technology facilitates research; commercially available biomarkers lacking; landmark study found that genome of kidney tumor from single patient lacks homogeneity; heterogeneity of tumors mitigates efficacy of targeted therapy; ideal biomarker excludes genes with heterogeneous expression and identifies genes common to all tumor cells in individual patient (stably expressed genes)

Immunotherapy: 9 targeted agents available (nivolumab most recently approved); immune response activated by delivery of tumor antigen by antigen-presenting cell to T cell; T cell responds by killing cancer cells; potency of T cells controlled by checkpoint inhibitors to prevent harmful autoimmune responses; checkpoint receptors include CTLA-4 and PD-1; checkpoint inhibitors activate immune responses; developed for treatment of cancer (eg, bladder cancer, kidney cancer); mutation of 19 genes required in kidney cancer; DNA sequence of each mutation and antigen expressed by tumor unique to individual patient; absence of common tumor-specific antigens for specific cancers precludes development of tumor-specific vaccines; most promising immunotherapy involves inhibiting checkpoints of immune response; tumors with greater number of mutations more likely to benefit from treatment with checkpoint inhibitors

Adjuvant therapy: locally advanced kidney cancer (eg, invasion into vein) associated with risk for recurrence of 50%; goal of adjuvant therapy to lower risk for recurrence in patients at high risk; findings of all phase III studies of adjuvant therapy for kidney cancer negative; approved adjuvant therapy for kidney cancer lacking; S-TRAC randomized controlled trial (Ravaud et al 2016) — found that sunitinib administered after nephrectomy associated with lower incidence of recurrence compared with placebo; sunitinib not approved by US Food and Drug Administration

Conclusions: consider laparoscopic partial nephrectomy for smaller renal tumors (and larger tumors, if operation technically feasible); many agents that target angiogenesis available for patients with metastatic kidney cancer; heterogeneity of clones in all solid tumors impedes development of biomarkers and therapeutic agents; regulation of immune checkpoints opportunity for immunotherapy; positive results of use of sunitinib in phase III study may lead to approval of first effective adjuvant therapy for kidney cancer

Readings

Barata PC, Rini BI: Treatment of renal cell carcinoma: Current status and future directions. CA Cancer J Clin 2017 Nov;67(6):507-524; Campbell S et al: Renal mass and localized renal cancer: AUA guideline. J Urol 2017 Sep;198(3):520-529; Mendiratta P et al: Emerging immunotherapy in advanced renal cell carcinoma. Urol Oncol 2017 Dec;35(12):687-693; Ravaud A et al: Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med 2016 Dec 8;375(23):2246-2254.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Kim was recorded at the 2017 Urologic Cancer Update, presented by Cedars-Sinai and held June 10, 2017, in Los Angeles, CA. For information on other CME programs from Cedars-Sinai, please visit cedars-sinai.edu/cmeurology. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

UR410402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.