Melanoma

Ideal settings, duration and frequency of follow-up for patients with melanoma

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Melanoma Institute Australia

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Barbour, A, A/Professor Alexander Guminski, Dr. Wendy Liu, Menzies, S, A/Professor Rachael Morton, Cancer Council Australia Melanoma Guidelines Working Party. Clinical question:What is the ideal setting, duration and frequency of follow-up for melanoma patients? . In: Clinical practice guidelines for the diagnosis and management of melanoma. Sydney: Melanoma Institute Australia. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=196934, cited 2023 Mar 31]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Melanoma.


Last modified:
21 January 2019 00:28:49

Systematic review evidence

Two randomised studies were identified, Murchie et al[1] and the MELFO study[2] to answer the question What are the ideal settings, duration and frequency of follow-up for patients with melanoma?. The remaining studies are retrospective cohort studies of timing and patterns of recurrence.

Follow-up setting

Current guidelines world-wide do not specify where routine follow-up should take place or who should do it.[3][4] However, it is becoming accepted by most [5][6][7] but not all [8][9][10] that patients themselves rather than doctors are likely to detect their own recurrence. Those studies reporting a high patient-detection rate attribute this to patients receiving thorough explanations of the signs and symptoms of recurrences and new primary melanomas. Despite such explanations, it is obvious that the ability of individual patients to detect recurrence varies. Some can identify recurrences that are not discernible to doctors, while others can be unaware of a large tumour mass. The existence of these latter patients perhaps explains the reticence of some centres to forego routine follow-up.

In Australia, with its heightened awareness of the disease, up to 75% of patients detect their own recurrences.[11] World-wide the mean percentage is 62%.[12] The UK Medical Research Council has designed a ‘framework for the design of an integrated follow-up program’.[13] One technique employed was to interview patients to determine their preferred follow-up requirements. Most supported follow-up by general practitioners, and felt that the main purpose of follow-up was reassurance that no recurrence was present.[13] However, there was concern over travelling times, costs, brevity of consultations, and poor continuity. Nearly all queried the experience and skill of the general practitioners and said training would be vital, with rapid access to specialist advice if necessary. In the study by Murchie et al,[1] the goal of patient reassurance was achieved by general practitioners offering phone consultations, thus avoiding frequent follow-up exams. Total skin examination, instruction in self-examination and the provision of more information were seen as desirable at visits to general practitioners. Other studies assessing patients’ opinions of the value of follow-up found that most considered routine follow-up worthwhile, with only a few considering that it was not.[4][14] While favouring follow-up, more than half the patients in these studies reported anxiety before each visit.

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Evidence summary and recommendations

Evidence summary Level References
There is consensus that follow up with a medical professional (GP, dermatologist, surgeon or medical oncologist) is beneficial for patients treated for melanoma in order to provide instruction for skin self-examination, examination for recurrence or new primary melanoma, and psychosocial support. IV [14], [13], [1], [4]
Evidence-based recommendationQuestion mark transparent.png Grade
Routine follow-up by the patient’s preferred doctor may be appropriate to emphasise sun smart behaviour and perform skin checks. 		C



Practice pointQuestion mark transparent.png

It may be beneficial for medical professionals conducting follow up examinations for melanoma patients to be familiar with skin examination and dermatoscopy.

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Follow-up duration and frequency

Standardized follow-up is considered an important component in the care of melanoma patients, aiming at early detection of recurrences and secondary melanomas. In the past, the choice of intervals between routine follow-up visits has been mostly arbitrary, but all suggested schedules have stipulated more frequent visits for patients with more advanced disease.[15] A systematic review by Cromwell et al[16] of current literature and consensus guidelines (n=104 studies) determined the variation in clinician practice patterns with respect to stage-specific surveillance of melanoma patients by country and physician speciality. Surveillance recommendations varied according to disease stage, country of origin, and physician speciality, and were related to the frequency of examination and use of diagnostic imaging and laboratory tests. There was a general consensus among countries and specialities for annual surveillance, self-examination by all patients, and that patients with high-risk stage III disease require regular clinical examinations. Significant differences were noted in the surveillance practices among countries; the most significant of which noted to surveillance intervals following the treatment of stage I disease. Recommendations for surveillance intervals and diagnostic imaging and laboratory evaluations varied by speciality. The greatest variation was seen in the recommended frequency follow-up visits for patients with stage I disease, which ranged from 2 to 4 times per year.[17][8][4][16] However, a review of current melanoma follow-up care and treatment from various centres around Germany, by Livingstone et al[18], found that adherence to these guidelines is poor: 13% perform reviews more frequently than recommended, while 31% perform follow up less frequently.[18] Moreover, 150/668 patients underwent diagnostic imaging procedures, despite these not being recommended.[18] Similarly, an Australian case series of 3747 stage I and II melanoma patients found that only 34% of stage I patients and 14% of stage II patients had the number of follow-up visits recommended in the Australian and New Zealand guidelines (2008) at a melanoma centre.[19]

There is broad consensus for 5 or 10-year, risk-adapted follow-up with increasing intervals between exams over time. Understanding recurrence patterns and hazard rates provides a rational basis for the timing and duration of follow up aimed at detecting melanoma recurrence or new primary melanoma. Hazard rates for recurrences have been reviewed in the German Guidelines and reveal differences between stages I–III within the first year after primary diagnosis. At stage I, hazard rates remained consistently low over a 5-year period. At stages II–III, there was an increased recurrence risk in year 1–2, which, after 3 years, again approached the same hazard rate as stage I. The highest recurrence rates were observed at stage III within the first year, followed by an approximation to stage II.[8] A more recent analysis confirmed these findings.[20] Stage IA showed consistently low hazard rates during the entire follow-up period of 10 years. After a period of 10 years, hazard rates at stages IB–III converge with stage IA rates.[21] Analyses of stage I–II patients with negative sentinel lymph nodes after sentinel lymph node biopsy revealed recurrences in 8.9%–10.1%, 78 % of which occurred within 18 months.[22] Recently, a large case series from Duke University of 11,615 patients with primary melanoma, revealed that 4,616 (40%) had at least one recurrence during long-term follow-up.[23] The risk of overall recurrence peaked at 12 months, where subsequent metastases appeared at progressively shorter intervals, with the time to development of second and third metastases peaking at 6.2 and 2.6 months, respectively. The risk of recurrence decreased over time, but did not reach zero. The most common site of initial recurrence was distant skin or nodes (59%). The second most common site for metastases was other distant metastases (16.5%), followed by local skin (16.1%) and lung (8.4%). There was an association between survival and the initial site of recurrence; the best survival was associated with local recurrence follow by regional nodal recurrence.

Overall, studies in stage I–III disease show that 47% of recurrences occur within the first year after diagnosis, 32% within the second year [8] and 80% within the first 3years.[24][25][26][27][17][11][8] Median time to recurrence of locoregional or regional lymph node metastases is consistently earlier than distant metastases (approximately 24 months).[28] For stage IIIC, all metastases occurred within 24 months.[29] The risk for recurrence for all stages after 10 years decreases to approximately 1%.[20][30][17][11] These data suggest discontinuation of follow-up after 10 years is warranted. Shorter follow up duration of 5 years has been proposed by some groups.[11][31] However, 20% of recurrences may occur more than 5 years after primary diagnosis for stages I and II.

Follow up beyond 10 years has been advocated by some groups due to the ongoing increased risk of new primary melanomas that may even occur more than 30 years after the diagnosis.[32][33][34][35] However, most secondary melanomas occur within the first two years after the primary diagnosis of melanoma, with a marked drop in incidence thereafter suggesting little benefit for long-term extension of follow up.[32][34][36] Australian data demonstrate that patients who develop one melanoma are at substantially increased life-long risk of developing second primary melanoma. This most pronounced for patients initially diagnosed under the age of 65 years.[37] Patients with additional risk factors (dysplastic nevus syndrome, family history) should be provided access to long-term dermatologic exams in addition to regular follow-up for at least 5 years.

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Evidence summary and recommendations

Evidence summary Level References
The peak risk period for recurrence is the first 12-24 months after the treatment of stage I-III melanoma, the risk being lowest for stage IA and highest for stage III.

At least 80% of recurrences occur with 3 years of diagnosis of primary melanoma, with less than 5% of recurrence occurring after 10 years. For primary melanoma, the majority of recurrences are locoregional or regional lymph nodes. For stage III melanoma, recurrence more than two years after complete surgical removal of disease is rare.

IV [17], [11], [8], [20], [24], [25], [26], [27], [30], [31]
The risk for subsequent melanomas for melanoma survivors is approximately 5 times higher than the general population. The lifetime risk remains constant. IV [8], [20], [32], [35]
Evidence-based recommendationQuestion mark transparent.png Grade
Risk adjusted follow up looking for recurrence based on stage at presentation should be considered over a time period of 5-10 years for stages I-II melanoma. For surgically resected stage III melanoma, the most intensive follow up should be for the first 3 years. 		C


Evidence-based recommendationQuestion mark transparent.png Grade
Melanoma survivors should be made aware of their risk of developing further primary melanomas, and of the consequent need for careful lifelong skin surveillance. 		C


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Frequency of follow-up for melanoma patients

The issue of adequate follow-up intervals plays a crucial role as to the question whether specific workup for metastasis may be rationally employed to improve mortality, morbidity, and quality of life in affected patients. The assumed risk for recurrence at a given point in time represents an essential parameter in these considerations and has been reviewed in the German Guidelines.[38] Some authors have suggested that intensified follow-up might be reasonable, as long as 95% of expected metastases have not been detected.[29]

In general, cost-benefit analyses have to be taken into account as well when considering at what point the risk for metastasis warrants an intensified follow-up program. Present studies mainly consider the cost of various procedures for metastasis detection in various schedules and patient groups.[12][17][18] There are no explicit cost-benefit analyses with respect to time-related threshold values for recurrence risks. Basseres et al[10] showed that, in 66% of cases, the interval between detected relapse and the previous follow-up exam was up to 4 months.'[10] These data suggest that follow-up intervals in patient groups at significant risk for recurrence should not exceed 3–4 months, provided it is desirable to identify asymptomatic recurrence.[10] However, authors from the Melanoma Institute of Australia (MIA) analysed the time-course a predictors for recurrence among over 3000 patients with stage I-II cutaneous melanoma.[39] Using these data, they evaluated the potential delay in diagnosis of recurrence or second primary melanoma using two different follow-up schedules: first was the NHMRC 2008 guidelines schedule; and the second involved follow-up annually for 10 years (stage I); every 6 months for 2 years, then annually for 8 years (stage IIA); or every 4 months for 2 years, every 6 months during year 3, then annually for 5 years (stages IIB and IIC).[39] This study assumes detection rates of 75% by patients themselves. For every 1,000 patients, the second schedule required 3000 fewer visits and only a small number of patients would experience a delay in the detection of recurrence or new primary melanoma. This proposed less frequent and a stage-based follow up schedule is being prospectively evaluated in a randomised study: the Melanoma Follow Up (MELFO) trial.[2] One-year results were recently reported for 180 patients and found that the less frequent follow up group reported significantly less cancer-related stress response symptoms.[2] The recurrence rate was 9% in both groups, mostly patient-detected and not physician-detected while costs of 1-year follow-up were reduced by 45% in the less frequent follow up group.[2]

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Evidence summary and recommendations

Evidence summary Level References
Intervals between routine visits are mostly arbitrary. However, all studies stress that the more advanced the disease, the more frequent the visits need to be. The interval between follow up exams and recurrence are in the order of 4 months or less. No other tests have significant value in patients with localised disease.

The available data suggest that less frequent follow up is not detrimental for overall survival.

IV [40], [41], [42], [43], [44], [45]
Evidence-based recommendationQuestion mark transparent.png Grade
Follow-up intervals:
  • Stage I: follow-up annually for 10 years
  • Stage IIA: every 6 months for 2 years, then annually for 8 years
  • Stage IIB and IIC: every 3 to 4 months for 2 years, every 6 months during year 3, then annually for 5 years.
  • Stage IIIA-C: every 3 months for 2 years, every 6 months during year 3, then annually for 5 years.
 C


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Value of follow-up

Some have questioned the value of any routine follow-up. Review of the advantages and disadvantages does not provide convincing evidence that regional control, quality of life or overall survival is increased through intense surveillance. Three studies showed no survival difference when comparing who detected recurrence.[9][4][46] Even if patient survival were increased due to the metastases being detected by a doctor at a routine follow-up visit rather than by the patients themselves, it would be hard to prove that this occurred as a result of the follow-up. Interpretation of data would be thwarted by possible lead-time bias. This latter problem was one flaw of the sole prospective study to date that claimed to demonstrate the efficacy of routine follow-up.[47] The reasons for the lack of valid prospective randomised trials assessing the value of routine follow-up are numerous, but foremost among them may be patient reluctance to accept a 50% risk of being assigned to the arm not receiving ultrasound or other follow-up. Enrolment of large numbers of patients with monitoring in excess of 15 years would be required because any difference in end-points would be small. There would also be a problem in determining recurrence rate and survival in patients not receiving routine ultrasound or follow-up.

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Evidence summary and recommendations

Evidence summary Level References
There is a lack of valid prospective studies of the efficacy of routine follow-up. No study has demonstrated an improvement in survival due to intense routine surveillance.

There may be some advantage in terms of patient reassurance and the detection of new melanomas

IV [46], [4], [9], [47]
Evidence-based recommendationQuestion mark transparent.png Grade
While it is important that clinicians weigh up the advantages and disadvantages of undertaking routine follow-up, individual patient’s needs should be considered before appropriate follow-up is offered. 		C


Notes regarding the recommendations

The recommendations given above are based on the best evidence currently available, but it is acknowledged that this is low-level evidence. Individual patients may prefer more frequent follow-up for reassurance, while others may prefer less frequent follow-up because of the anxiety provided by the follow-up visits or the time and expense associated with attendance for follow-up. Routine radiological follow up for stage IIC and III melanoma may detect recurrence sooner, possibly leading to better outcome by allowing treatment with drugs, such as immunotherapy drugs, to start earlier. However, while early drug treatment of recurrent melanoma might improve survival, there is currently no evidence showing this. Thus, the recommendations are a reasonable compromise which, reinforced by good patient education, should ensure that most melanoma recurrences are detected promptly and new primary melanomas are diagnosed early.

Go to previous section: Follow up after initial definitive treatment for each stage of melanoma.

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References

  1. ↑ 1.0 1.1 1.2 Murchie P, Nicolson MC, Hannaford PC, Raja EA, Lee AJ, Campbell NC. Patient satisfaction with GP-led melanoma follow-up: a randomised controlled trial. Br J Cancer 2010 May 11;102(10):1447-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20461089.
  2. ↑ 2.0 2.1 2.2 2.3 Damude S, Hoekstra-Weebers JE, Francken AB, Ter Meulen S, Bastiaannet E, Hoekstra HJ. The MELFO-Study: Prospective, Randomized, Clinical Trial for the Evaluation of a Stage-adjusted Reduced Follow-up Schedule in Cutaneous Melanoma Patients-Results after 1 Year. Ann Surg Oncol 2016 Sep;23(9):2762-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27194552.
  3. ↑ Bain NS, Campbell NC, Ritchie LD, Cassidy J. Striking the right balance in colorectal cancer care--a qualitative study of rural and urban patients. Fam Pract 2002 Aug;19(4):369-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12110557.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Baughan CA, Hall VL, Leppard BJ, Perkins PJ. Follow-up in stage I cutaneous malignant melanoma: an audit. Clin Oncol (R Coll Radiol) 1993;5(3):174-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8347541.
  5. ↑ Jillella A, Mani S, Nair B, Poo WJ, Bolognia J, Ariyan S et al. The role for close follow-up of melanoma patients with AJCC stage I-III: a preliminary analysis. Proc Am Soc Clin Oncol 1995;14.
  6. ↑ Kersey PA, Iscoe NA, Gapski JA, Osoba D, From L, DeBoer G, et al. The value of staging and serial follow-up investigations in patients with completely resected, primary, cutaneous malignant melanoma. Br J Surg 1985 Aug;72(8):614-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/4027532.
  7. ↑ Ruark DS, Shaw HM, Ingvar C, McCarthy WH, Thompson JF. Who detects the primary recurrence in stage I cutaneous melanoma: patient or doctor? Melanoma Res 1993;3(Supplement 1):44.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Poo-Hwu WJ, Ariyan S, Lamb L, Papac R, Zelterman D, Hu GL, et al. Follow-up recommendations for patients with American Joint Committee on Cancer Stages I-III malignant melanoma. Cancer 1999 Dec 1;86(11):2252-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10590365.
  9. ↑ 9.0 9.1 9.2 Hofmann U, Szedlak M, Rittgen W, Jung EG, Schadendorf D. Primary staging and follow-up in melanoma patients--monocenter evaluation of methods, costs and patient survival. Br J Cancer 2002 Jul 15;87(2):151-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12107834.
  10. ↑ 10.0 10.1 10.2 10.3 Bassères N, Grob JJ, Richard MA, Thirion X, Zarour H, Noe C, et al. Cost-effectiveness of surveillance of stage I melanoma. A retrospective appraisal based on a 10-year experience in a dermatology department in France. Dermatology 1995;191(3):199-203 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8534937.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 Francken AB, Shaw HM, Accortt NA, Soong SJ, Hoekstra HJ, Thompson JF. Detection of first relapse in cutaneous melanoma patients: implications for the formulation of evidence-based follow-up guidelines. Ann Surg Oncol 2007 Jun;14(6):1924-33 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17357855.
  12. ↑ 12.0 12.1 Francken AB, Bastiaannet E, Hoekstra HJ. Follow-up in patients with localised primary cutaneous melanoma. Lancet Oncol 2005 Aug;6(8):608-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16054572.
  13. ↑ 13.0 13.1 13.2 Murchie P, Hannaford PC, Wyke S, Nicolson MC, Campbell NC. Designing an integrated follow-up programme for people treated for cutaneous malignant melanoma: a practical application of the MRC framework for the design and evaluation of complex interventions to improve health. Fam Pract 2007 Jun;24(3):283-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17449893.
  14. ↑ 14.0 14.1 Dancey A, Rayatt S, Courthold J, Roberts J. Views of UK melanoma patients on routine follow-up care. Br J Plast Surg 2005 Mar;58(2):245-50 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15710122.
  15. ↑ Marciano NJ, Merlin TL, Bessen T, Street JM. To what extent are current guidelines for cutaneous melanoma follow up based on scientific evidence? Int J Clin Pract 2014 Jun;68(6):761-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24548269.
  16. ↑ 16.0 16.1 Cromwell KD, Ross MI, Xing Y, Gershenwald JE, Royal RE, Lucci A, et al. Variability in melanoma post-treatment surveillance practices by country and physician specialty: a systematic review. Melanoma Res 2012 Oct;22(5):376-85 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22914178.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 Dicker TJ, Kavanagh GM, Herd RM, Ahmad T, McLaren KM, Chetty U, et al. A rational approach to melanoma follow-up in patients with primary cutaneous melanoma. Scottish Melanoma Group. Br J Dermatol 1999 Feb;140(2):249-54 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10233217.
  18. ↑ 18.0 18.1 18.2 18.3 Livingstone E, Krajewski C, Eigentler TK, Windemuth-Kieselbach C, Benson S, Elsenbruch S, et al. Prospective evaluation of follow-up in melanoma patients in Germany - results of a multicentre and longitudinal study. Eur J Cancer 2015 Mar;51(5):653-67 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25638778.
  19. ↑ Memari N, Hayen A, Bell KJ, Rychetnik L, Morton RL, McCaffery K, et al. How Often Do Patients with Localized Melanoma Attend Follow-Up at a Specialist Center? Ann Surg Oncol 2015 Dec;22 Suppl 3:S1164-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25963479.
  20. ↑ 20.0 20.1 20.2 20.3 Leiter U, Buettner PG, Eigentler TK, Bröcker EB, Voit C, Gollnick H, et al. Hazard rates for recurrent and secondary cutaneous melanoma: an analysis of 33,384 patients in the German Central Malignant Melanoma Registry. J Am Acad Dermatol 2012 Jan;66(1):37-45 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21700361.
  21. ↑ Leiter U, Marghoob AA, Lasithiotakis K, Eigentler TK, Meier F, Meisner C, et al. Costs of the detection of metastases and follow-up examinations in cutaneous melanoma. Melanoma Res 2009 Feb;19(1):50-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19430406.
  22. ↑ Stucky CC, Gray RJ, Dueck AC, Wasif N, Laman SD, Sekulic A, et al. Risk factors associated with local and in-transit recurrence of cutaneous melanoma. Am J Surg 2010 Dec;200(6):770-4; discussion 774-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21146019.
  23. ↑ Salama AK, de Rosa N, Scheri RP, Pruitt SK, Herndon JE 2nd, Marcello J, et al. Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy. PLoS One 2013;8(3):e57665 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23516415.
  24. ↑ 24.0 24.1 Fusi S, Ariyan S, Sternlicht A. Data on first recurrence after treatment for malignant melanoma in a large patient population. Plast Reconstr Surg 1993 Jan;91(1):94-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8416544.
  25. ↑ 25.0 25.1 Hohnheiser AM, Gefeller O, Göhl J, Schuler G, Hohenberger W, Merkel S. Malignant melanoma of the skin: long-term follow-up and time to first recurrence. World J Surg 2011 Mar;35(3):580-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21125274.
  26. ↑ 26.0 26.1 Kelly JW, Blois MS, Sagebiel RW. Frequency and duration of patient follow-up after treatment of a primary malignant melanoma. J Am Acad Dermatol 1985 Nov;13(5 Pt 1):756-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/4078070.
  27. ↑ 27.0 27.1 Martini L, Brandani P, Chiarugi C, Reali UM. First recurrence analysis of 840 cutaneous melanomas: a proposal for a follow-up schedule. Tumori 1994 Jun 30;80(3):188-97 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8053075.
  28. ↑ Zogakis TG, Essner R, Wang HJ, Foshag LJ, Morton DL. Natural history of melanoma in 773 patients with tumor-negative sentinel lymph nodes. Ann Surg Oncol 2007 May;14(5):1604-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17333418.
  29. ↑ 29.0 29.1 Romano E, Scordo M, Dusza SW, Coit DG, Chapman PB. Site and timing of first relapse in stage III melanoma patients: implications for follow-up guidelines. J Clin Oncol 2010 Jun 20;28(18):3042-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20479405.
  30. ↑ 30.0 30.1 Rueth NM, Groth SS, Tuttle TM, Virnig BA, Al-Refaie WB, Habermann EB. Conditional survival after surgical treatment of melanoma: an analysis of the Surveillance, Epidemiology, and End Results database. Ann Surg Oncol 2010 Jun;17(6):1662-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20165985.
  31. ↑ 31.0 31.1 Garbe C, Leiter U, Ellwanger U, Blaheta HJ, Meier F, Rassner G, et al. Diagnostic value and prognostic significance of protein S-100beta, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patients. Cancer 2003 Apr 1;97(7):1737-45 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12655531.
  32. ↑ 32.0 32.1 32.2 Goggins WB, Tsao H. A population-based analysis of risk factors for a second primary cutaneous melanoma among melanoma survivors. Cancer 2003 Feb 1;97(3):639-43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12548605.
  33. ↑ Johnson TM, Hamilton T, Lowe L. Multiple primary melanomas. J Am Acad Dermatol 1998 Sep;39(3):422-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9738776.
  34. ↑ 34.0 34.1 Kang S, Barnhill RL, Mihm MC Jr, Sober AJ. Multiple primary cutaneous melanomas. Cancer 1992 Oct 1;70(7):1911-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1525766.
  35. ↑ 35.0 35.1 Pomerantz H, Huang D, Weinstock MA. Risk of subsequent melanoma after melanoma in situ and invasive melanoma: a population-based study from 1973 to 2011. J Am Acad Dermatol 2015 May;72(5):794-800 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25769192.
  36. ↑ Brobeil A, Rapaport D, Wells K, Cruse CW, Glass F, Fenske N, et al. Multiple primary melanomas: implications for screening and follow-up programs for melanoma. Ann Surg Oncol 1997 Jan;4(1):19-23 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8985513.
  37. ↑ Karahalios E, Dallas E, Thursfield V, Simpson J, Farrugia H, Giles G.. Second Primary Cancers in Victoria. Melbourne: Victorian Cancer Registry Cancer Epidemiology Centre Cancer Council Victoria; 2009 Available from: http://www.cancervic.org.au/research/registry-statistics/cancer-in-victoria/second-primary-cancers-victoria.
  38. ↑ McCarthy WH, Shaw HM, Thompson JF, Milton GW. Time and frequency of recurrence of cutaneous stage I malignant melanoma with guidelines for follow-up study. Surg Gynecol Obstet 1988 Jun;166(6):497-502 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3375961.
  39. ↑ 39.0 39.1 Turner RM, Bell KJ, Morton RL, Hayen A, Francken AB, Howard K, et al. Optimizing the frequency of follow-up visits for patients treated for localized primary cutaneous melanoma. J Clin Oncol 2011 Dec 10;29(35):4641-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22067399.
  40. ↑ Bafounta ML, Beauchet A, Chagnon S, Saiag P. Ultrasonography or palpation for detection of melanoma nodal invasion: a meta-analysis. Lancet Oncol 2004 Nov;5(11):673-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15522655.
  41. ↑ Machet L, Nemeth-Normand F, Giraudeau B, Perrinaud A, Tiguemounine J, Ayoub J, et al. Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients. Br J Dermatol 2005 Jan;152(1):66-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15656802.
  42. ↑ Blum A, Schlagenhauff B, Stroebel W, Breuninger H, Rassner G, Garbe C. Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma: results of a prospective study of 1288 patients. Cancer 2000 Jun 1;88(11):2534-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10861430.
  43. ↑ Brountzos EN, Panagiotou IE, Bafaloukos DI, Kelekis DA. Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma. Oncol Rep 2003 Mar;10(2):505-10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12579298.
  44. ↑ Schmid-Wendtner MH, Paerschke G, Baumert J, Plewig G, Volkenandt M. Value of ultrasonography compared with physical examination for the detection of locoregional metastases in patients with cutaneous melanoma. Melanoma Res 2003 Apr;13(2):183-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12690303.
  45. ↑ Voit C, Mayer T, Kron M, Schoengen A, Sterry W, Weber L, et al. Efficacy of ultrasound B-scan compared with physical examination in follow-up of melanoma patients. Cancer 2001 Jun 15;91(12):2409-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11413532.
  46. ↑ 46.0 46.1 Binder M, Kittler H, Steiner A, Dorffner R, Wolff K, Pehamberger H. Lymph node sonography versus palpation for detecting recurrent disease in patients with malignant melanoma. Eur J Cancer 1997 Oct;33(11):1805-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9470837.
  47. ↑ 47.0 47.1 Garbe C, Paul A, Kohler-Späth H, Ellwanger U, Stroebel W, Schwarz M, et al. Prospective evaluation of a follow-up schedule in cutaneous melanoma patients: recommendations for an effective follow-up strategy. J Clin Oncol 2003 Feb 1;21(3):520-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12560444.

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