The Melanoma Patient Symposium - Science to Survivorship When Do I Consider Myself Cured? 26 September 2009 Jeffrey E. Gershenwald, MD, FACS Professor of Surgery, Dept. of Surgical Oncology Professor, Dept. of Cancer Biology Vice-Chair, AJCC Melanoma Task Force
Doc. I know you just treated the early-stage melanoma on my leg a few weeks ago and everything looked good.margins clear, sentinel node negative.do I need to worry any more? I had a melanoma 6 years ago on my arm. My sentinel node was positive and I had a lymph node dissection. but I ve had no problems so far.am I out of the woods?
When Do I Consider Myself Cured? Overview Can we predict the future? Not exactly Over time, is my risk of developing problems from melanoma the same as when I was first diagnosed? Generally speaking..no
When Do I Consider Myself Cured? Overview Current status and new directions in staging and assessment of prognosis 2009 AJCC melanoma staging system Contemporary analytic approaches to prognosis Risk of 2 nd primary melanoma Follow-up strategies?
Let s Talk About Statistics! Tremendous strides in melanoma staging have been made (eg, AJCC/UICC) Limitations exist in traditional staging systems: # of characteristics (patient, tumor, etc.) that can be included is limited Inability to use continuous variables Estimates of survival only based on time of diagnosis TNM staging applies to large cohorts of patients but does not incorporate all the combinations of prognosis or estimates of cancer-specific survival in individual patient settings:
Improvements to Melanoma Staging and Estimating Prognosis New statistical models are being built Better understanding and use of surgical staging to identify patients who have clinically undetectable (microscopic) disease in regional lymph nodes e.g., sentinel lymph node biopsy
2009 (7 th Ed.) AJCC Manual for Staging Cancer (To be published October 2009)
2009 AJCC Melanoma Staging System 7 th Edition AJCC Manual for Staging Cancer In Press, 2009.
New Directions in Prognostic Assessment Leveraging the current staging system Contemporary statistical modeling that includes multiple prognostic factors New statistical models Conditional probability
Improvements to Melanoma Staging and Estimating Prognosis New statistical models : Use of multiple characteristics Use continuous variables (e.g., tumor thickness 2.3 mm, not 2-4 mm) Estimate survival for patients after treatment and at any time during follow-up (more on this soon ) Enhanced ability to combine prognostic features for estimates of cancer-specific survival in individual patient settings:
www.melanomaprognosis.org
Doc You know, it s been 4 years since you removed the melanoma deposits under my arm when you performed a lymph node dissection. I still think about my melanoma a lot. Is there any hope for the future. how much do I need to worry about this coming back again?
Conditional Probability Risk of something happening if it has not yet happened after a given period of time. I had a melanoma 6 years ago on my arm I ve had no problems thus far. am I out of the woods?
Conditional Probability Work in Progress Xing et al., In Press, 2009
Improvements to Melanoma Staging and Estimating Prognosis New statistical models are being built Better understanding and use of surgical staging to identify patients who have clinically undetectable (microscopic) disease in regional lymph nodes
Nodal Metastases - Evolving Paradigm Then Macroscopic Gershenwald et al., J Clin Oncol, 1999
AJCC Database - Regional LN (Stage III) 2002-6th edition Macroscopic 45% N=675 N=825 Microscopic 55%
Gershenwald et al., J Clin Oncol, 1999 Nodal Metastases - Evolving paradigm Then Macroscopic Now Positive-SLN
AJCC Database - Regional LN (Stage III) Paradigm Shift Macroscopic 19% N=560 N=2334 Microscopic 81%
T4b.45 ±.019.67 ±.036 AJCC 2008 *Stage-appropriate use of SLN biopsy AJCC Collaborative Melanoma Database Stage I/II 5-Year Survival Rate by T- Classification T-Classification 6 th Edition 7th Edition SLN Subset* T1a.95 ±.004.97 ±.011 T1b.91 ±.010.95 ±.015 T2a.89 ±.007.95 ±.006 T2b.77 ±.017.86 ±.020 T3a.79 ±.012.85 ±.015 T3b.63 ±.015.76 ±.025 T4a.67 ±.024.76 ±.036
7 th Edition AJCC (2009) Collaborative Melanoma Database Stage III survival Curves by Substage 1.0 0.9 0.8 Survival Function 0.7 0.6 0.5 0.4 0.3 0.2 IIIA (n=1,196) IIIB (n=1,391) IIIC (n=720) Stage IIIA (2002) 0.1 0.0 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 Survival Time in Years Implications for Patient Counseling & Management & Contemporary Adjuvant Clinical Trial Design
Am I at risk for development of another primary melanoma? Unfortunately, YES Estimated 5% risk over 5-years 25-fold increased risk over general population Surveillance is important in patients with a history of melanoma EVEN if risk of METASTASIS (ie, spread) is low Self-examination (new 1 o & recurrences) Dermatologic surveillance
Surveillance is Very Important Dr. Hymes earlier today ABCDEs Anything new or changing Ugly duckling sign When in doubt, check it out!
The ABCDEs of Melanoma Diagnosis Asymmetry One half of the lesion is shaped differently than the other Border The border of the lesion is irregular, blurred, or ragged Color Inconsistent pigmentation, with varying shades of brown and black Evolution History of change in the lesion Diameter >6 mm, or a progressive change in size Photos courtesy of the American Cancer Society.
Evidence-Based Follow-Up of the Melanoma Patient
Houston, do we have a problem? No consensus on follow-up guidelines for pts with melanoma Generally, based on risk of recurrence However, the challenge : Evolution of treatment variable and not fully understood impact on patterns of recurrence and survival Evolution of prognostic factors stage-specific heterogeneity of disease Technology is ever-expanding (and not yet perfect)
Imaging Studies in Melanoma Background The Challenge Prominent component of the initial staging workup, preoperative assessment, and follow-up. Despite widespread use, benefits not entirely clear. Low rates of detection > high false-positive NCCN consensus panel varying opinion - utility generally dependent upon stage Currently no uniform policies regarding stagespecific utilization of imaging studies
NCCN Recommendations H&P Routine Imaging Stage IA 3-12 months for 5y Not recommended Stage IB, IIA Stage IIB, IIC, III 3-6 for 2y, 3-12 for 2y, then annual 3-6 for 2y, 3-12 for 2y, then annual none CXR optional Consider CTs Routine Labs none none LDH, CBC optional Notes consider CT scans to follow-up specific signs/symptoms and for >=IIB
Australia-New Zealand Guidelines (2008-9)* H&P Other imaging Stage I annually Stage II-III 3-4 mos x 5y, then annually Consider ultrasound (if skilled personnel available) *Patients on protocol - followed per protocol Note: 80% of recurrences usually occur <3yrs Guidelines stress careful history and PE Pt self-education is important - 62%-75% of patients detect their own recurrence (sign, sx, or planned exam) and up to ½ detect their own 2 nd primary SMU (2008) IIA, 6 mos x 2y; IIB-IIC, 4 mos x 2y, 6 mos x 1y, then annually
M. D. Anderson Follow-up H&P CXR LDH, Other routine imaging Stage IA 6 mos x 2-4 y, then annually (Consider annual) none None Stage IB/IIA (SLN negative) 4-6 mos x 2-5 y, then annually (Consider) (cons ider) none Stage IIB, 3-4 mos x 2 y, then 6 Each visit Each See notes IIC, III* Notes: mos x 3 y, then annually visit Additional staging per protocol, if applicable Stage III - consider interval CT/MRI (and PET/CT) based on symptoms and pattern/extent of disease
How can we enhance follow-up for our patients with melanoma? Better understand patterns of metastasis and survival rates in contemporary era of SLN biopsy Identification pts in whom less/more aggressive follow-up is warranted Stage-specific conditional probability tailor follow-up strategy to risk using contemporary analytic approaches Molecular endpoints - work in progress Educating and empowering our patients is very important!!
Navigating the Web What information do you find helpful? What information do you find confusing? What are we missing how can we help?
Thank you!