MELANOMA CRITICAL DEBATES - PART 6 pot

mended. The authors calculated that the cost to detect one metastasis was 9, 20 or 36 times higher when chest radiograph, abdominal ultrasound or both were used, as compared to regular clinical examination. Weiss et al. [3] inves- tigated how recurrence was diagnosed in 145 patients treated in a clinical study. In 99 patients (68%) symptoms signalled the recurrence of disease, and physical examination of asymptomatic patients led to the detection of recur- rence in 37 patients (26%). Only nine patients (6%) with recurrent disease had abnormal chest radiographs. A retrospective analysis of 1004 patients with stage I or II malignant melanoma treated at Roswell Park Cancer Institute between 1971 and 1995 analysed impact of method of recurrence detection on survival [5]. Of note in this series only 7% of patients had AJCC pT4 tumours. Constitutional symp- toms heralded 17% of 154 recurrences, physical examination 72% (over half patients detected) and chest radiograph 11% (17 patients). Overall survival curves were superimposable for patients who detected their recurrence them- selves and those whose recurrence was detected by the physician. Survival was identical in patients whose pulmonary recurrence was picked up by chest ra- diograph or by symptoms. However, nine of the 17 patients with recurrences detected by chest radiograph alone underwent curative surgical excision with median survival of 24 months from diagnosis of recurrence, compared to 15 months in patients who received chemotherapy for unresectable disease. We estimate that, for the 1004 patients followed up according to protocol for a median of 6.1 years, with 174 recurring at a median of 2.5 years and 830 pa- tients not recurring during reported follow-up, over 10000 chest radiograph investigations would have been performed to detect the 17 recurrences. Although the patient dose from a single chest radiograph is minimal, the cumulative dosage over the study period for say 10 radiographs is not. Unfor- tunately, no information was provided about false-positive chest radiograph results and the follow-up investigations to clarify those further. The risk of recurrence and death from melanoma can be calculated for pa- tients according to the thickness of their primary lesion, and has been reported as a function of time since diagnosis [23–29]. For all melanomas, the risks of first recurrence and death are highest in the first years following excision and fall gradually over the next 10 years. However, a small risk of death from melanoma relapse persists at 10 years for even the thinnest melanomas. Most recurrences are diagnosed by physical examination and the patients can be taught to perform this proficiently themselves [26]. To date there are no prospective studies to assess the use of imaging in follow-up, and so the use of imaging in surveillance will ultimately depend on clinicians’ interpretation of the published retrospective data and available financial resources. The pub- lished evidence argues strongly against follow-up imaging of any sort in pa- tients with stage I and II disease. 140 CHAPTER 11 Stage III melanoma Staging Sentinel node dissection (SND) is increasingly used to determine pathological nodal status in patients with intermediate or thick primaries. The rationale of SND is the demonstration of orderly progression of melanoma nodal metastases, coupled with the ability to identify the first draining node using intraoperative lymphatic mapping guided by vital blue dye or radiolym- phoscintigraphy. SND is now variously accepted as standard practice in Europe and the USA, but most studies of the value of imaging in stage III patients have included patients that were conventionally staged, rather than by SND. Patients with clinical lymph node involvement by melanoma often have thicker primaries and their risk of harbouring further metastases is substan- tially higher than for stage I and II patients. Buzaid et al. [30] were the first to analyse the value of staging CT scans in patients with lymph node involvement at diagnosis or first recurrence. They reviewed the records of 89 asymptomatic patients with stage III disease and with normal LDH and chest radiograph who underwent staging CTs. A further 10 patients were described who were excluded from analysis based on either symptoms suggestive of distant dis- ease, raised LDH or positive chest radiograph. Overall, even in group of ‘high risk’ patients, the positive predictive value of CT was less than 25%. True-pos- itive findings were seen in six patients, false-positive in 20 and true-negative in 63 patients. Kuvshinoff et al. [31] published the Memorial Sloan Kettering experience with 347 asymptomatic patients, of which 136 had CT scans of chest, ab- domen and pelvis. A total of 788 scan results were analysed retrospectively, with 33 (4.3%) confirmed instances of metastatic melanoma and 66 (8.4%) false-positives. Body CT scans further identified five second primaries, four at early stages. When only the patients who had combined scans of chest, ab- domen and pelvis were analysed separately, the overall yield was of 11 true- positive scans (8.1%) for melanoma and three for second primaries. When patients with abnormal LDH or chest radiograph were excluded, the diagnos- tic yield for melanoma was 4.4% (or for melanoma and second primaries 5.9%). Management of nine of 14 patients with positive findings was altered by the CT findings, and in three patients a complete resection of identified tu- mour was possible. Pertinently, the authors also analysed the diagnostic yield of scans as affected by the location of the primary tumour. Pelvic scans were of no use for primaries above the diaphragm, and the yield of chest scans was lowest for patients with lower extremity primaries and inguinal lymphadenopathy. IMAGING AND INVESTIGATION OF MELANOMA PATIENTS 141 A further study analysed the value of CT in detecting neck node metastases in patients with thin and intermediate thickness head or neck melanoma [32]. Twenty-six patients, of whom 18 had clinically involved lymph nodes, had CT evaluation before undergoing neck dissections. Although the diagnostic accu- racy was greater than palpation, in seven patients small nodal metastases were missed on the scan when pathology data were reviewed. Recently, the use of 2-fluoro-2-deoxyglucose (FDG)-PET scanning was re- ported for detection of melanoma metastases [33,34]. Although access to PET is at present limited, it is a promising tool in staging of melanoma which ap- pears to have a higher sensitivity and specificity than CT. Between 1994 and 1996, 100 patients with melanomas thicker than 1.5mm underwent an exten- sive staging programme [33], consisting of chest radiograph, abdominal ul- trasound and high-resolution sonography of regional nodes, CT of chest and abdomen and MRI of the brain, together with whole body PET scans. Overall, sensitivity, specificity and accuracy of PET (91.8, 94.4 and 92.1%, respec- tively) were significantly higher than for conventional imaging, the other modalities combined (57.5, 45 and 55.7%, respectively). PET was superior in imaging of lymph nodes, abdomen and mediastinum, while CT was superior for definition of lung nodules. The authors concluded that a single PET scan would replace all other conventional imaging techniques for staging malig- nant melanoma. One reason for the superiority of PET is that metabolic changes often precede morphological changes, and foci of melanoma smaller than the threshold above which disease is considered present on CT already are visualized by PET imaging. Superior sensitivity (94.2%) and specificity (83.3%) for PET scans compared to CT (55.3 and 84.4%, respectively) is also claimed by another group [34], who indicated 5mm as the threshold of detec- tion melanoma size. FDG-PET staging of regional lymph nodes prior to SND was investigated. In contrast to an earlier report [35], Wagner et al. [36] claimed that PET was an insensitive indicator of occult nodal disease in 70 patients when compared to histological results of SND and clinical course. Sensitivity was merely 16.7%, with median tumour volume of 4.3mm 3 . However, specificity was very good (95.8%), which may be of relevance in those centres where SND is not routinely performed, as this makes FDG-PET still the most accurate non- invasive method of lymph node assessment. Surveillance Patients with AJCC stage III melanoma have a chance of relapse of approxi- mately two-thirds, with two-thirds of those occurring at distant sites [37]. Furthermore, the majority of relapses occur early. Surveillance practice varies widely [2] and involves use of chest radiograph, CT of chest, abdomen, pelvis 142 CHAPTER 11 and brain or MRI. There may be benefits in early detection of recurrence, and preliminary reports on earlier identification of relapse in high-risk patients followed up by PET scans than conventional imaging are encouraging. It is to be hoped that prospective randomized studies evaluating clinical and survival impact of PET surveillance compared to conventional follow-up will be forthcoming. Stage IV melanoma Staging and response assessment As curative approaches to patients with extensive melanoma spread are lack- ing, for some patients receiving conventional treatment assessment by chest radiograph or abdominal ultrasound may be sufficient. Differential responses are rare, and extrapolation of response in the imaged metastases to the others is reasonable. For monitoring of response, reproducibility is of key impor- tance, and thus repeat imaging should be the same as initial evaluation. More extensive imaging may be required for patients treated in the context of clini- cal studies. The ability to examine large tissue volumes rapidly and reproducibly makes CT the preferred option. MRI may be useful as a problem solving tool or for specific indications (e.g. cord compression, leptomeningeal metastasis). The role of PET is unclear in patients with evident metastases. For some treatment regimens, toxicity may result from treatment of un- suspected brain metastases. These patients will usually be investigated with contrast enhanced CT of the body and examination of the brain at the end of the body examination suffices to assess metastatic disease. Problem solving by multidisciplinary meeting For most patients the information provided from imaging will confirm the clinical impression of disease activity and extent. For a few there are discrep- ancies or other problems requiring clinicopathoradiological discussion. Such discussion works best within a multidisciplinary team which meets regularly to review problem cases. An understanding of the sites and appearance of melanoma metastases is key to their recognition (e.g. advanced melanoma may spread to uncommon sites, such as spleen and muscle) (Figs 11.2 and 11.3). Familiarity with these patterns avoids investigation for alternative causes. What are the options for dealing with uncertainty? Often the fuller discus- sion within the multidisciplinary meeting of the clinical problem suffices. As discussed, imaging involves first detection of abnormalities and then their IMAGING AND INVESTIGATION OF MELANOMA PATIENTS 143 characterization. However, the characterization has a clinical context and management impact. Thus, if a lesion is detected which might be metastatic in a patient already committed to systemic chemotherapy, its characterization would not alter management. However, its characterization is important to determine context; would such treatment be in an adjuvant or metastatic setting? Definitive characterization requires histological analysis following surgi- cal excision or image guided biopsy. Only a positive biopsy result is reliable, as sampling error as well as technical failure may result in false-negative find- ings. In certain circumstances, addition of another imaging test may be diag- nostic. In staging it is usual to use the best and most rapid methods for detection and characterization of metastatic disease but there is a compromise to be reached between using many specialized tests or a single multipurpose examination (e.g. CT). MRI is a valuable supplementary test for melanoma metastases as they may have characteristic high signal on T1-weighted images (Fig. 11.4). 144 CHAPTER 11 Fig. 11.2 Contrast enhanced upper abdominal CT showing splenic metastases (arrows). Fig. 11.3 Contrast enhanced pelvic CT showing left inguinal nodal metastases (arrows) and unsuspected bilateral buttock metastases. If the nature of abnormalities cannot be ascertained by any of these methods — or if biopsy is considered too invasive — the other option is a wait and watch policy. This is particularly suitable when a patient is asympto- matic or when active management would not be prejudiced by a delay in characterization — during which interval the lesion may grow or others may appear. Small pulmonary nodules can cause problems of characteriza- tion for CT (Fig. 11.5) as well as chest radiography. Other common indeter- minate lesions are subcentimetre liver nodules which could represent benign entities (cyst, haemangioma) and adrenal nodules. Recommendations for use of imaging in melanoma patients For patients not treated or followed up in the context of clinical trials, imaging IMAGING AND INVESTIGATION OF MELANOMA PATIENTS 145 Fig. 11.4 (a) Contrast enhanced upper abdominal CT showing hyperdense liver metastases (arrows); and (b) contemporaneous T1-weighted MRI of the liver at a similar level showing high signal change within these and additional lesions not seen with CT. Diagnosis: melanoma metastases in a patient with a previous breast cancer and melanoma. (a) (b) protocols should be based on the prevalence of metastases in the correspond- ing risk group, based on pathological criteria for the primary lesion and in- transit, satellite and locoregional lymph node metastases (Table 11.1). There are few prospective trials that allow estimates of sensitivity and specificity of imaging modalities in the various risk groups, and these are urgently needed. In the past, increasing availability and perceived higher sensitivity of newer imaging techniques led to their use in many patients with melanoma in the absence of any evidence that they improve staging and outcome in early stage melanoma. There is little evidence to support use of any radiological in- vestigations in patients with thin melanoma. For stage I and IIA melanomas (primary tumours <4mm thickness), chest radiograph and CT scans have a poor ratio of true-positive:false-positive findings. Stage I patients do not ben- efit from any form of imaging for staging, while use of chest radiograph and 146 CHAPTER 11 Fig. 11.5 Lung CT showing: (a) indeterminate subpleural nodules; and (b) after 2 months of observation showing an increase in the size and number of nodules suggesting metastatic disease. (a) (b) CT scans for stage II is controversial and both diagnostic accuracy and yield are poor. We thus recommend that these patients have a baseline chest radi- ograph only, against which future suspected relapse can be assessed. Occa- sionally, clear-cut pulmonary metastases will be revealed. More likely, indeterminate nodules will be found and will require a repeat radiograph in 2–3 months. Patients with melanomas thicker than 4mm (stage IIB) have a higher risk of subclinical metastases. There are thus grounds to investigate them similarly to clinical stage III but at present principally in the context of clinical trials. More data are required on the use of imaging in staging and surveillance of stage IIB disease. For asymptomatic stage III patients with normal baseline blood tests, chest radiograph and CT tailored to the primary site seem warranted, given that these investigations will pick up clinically occult disease in 10–20% of pa- tients. This is the group of patients who may be offered adjuvant interferon therapy, a toxic and expensive treatment, justifying the need to exclude metastatic disease. PET scans, where available, may be a better tool than CT for staging and surveillance in these high-risk patients. Choice of imaging modality in patients with distant metastases will be in- formed by the goals of treatment, either radical or palliative. IMAGING AND INVESTIGATION OF MELANOMA PATIENTS 147 Table 11.1 Practical recommendations for initial staging investigations Stage Location of primary tumour Recommendation I, IIA Any Chest radiograph as baseline If abnormal repeat in 2–3 months. No other imaging unless clearly abnormal film with high index of suspicion IIB, III Head and neck CT chest* CT neck if no lymph node dissection planned IIB, III Thorax, upper extremities CT chest*, liver No indication for CT pelvis IIB, III Lower torso, lower extremities CT chest*, abdomen and pelvis IV Any CT chest*, abdomen and pelvis or Chest radiograph and abdominal ultrasound *Also chest radiograph if metastases >1cm present, as this may substitute for follow-up. Abbreviation: CT, computed tomography. References 148 CHAPTER 11 1 Balch CM, Reintgen DS, Kirkwood JM, et al. In: de Vita VT, Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology, 5th edn. Philadelphia: Lippincott-Raven, 1997; 1947–94. 2Provost N, Marghoob AA, Kopf AW, DeDavid M, Wasti Q, Bart RS. Laboratory tests and imaging studies in patients with cutaneous malignant melanomas: a survey of experienced physicians. J Am Acad Dermatol 1997; 36: 711–20. 3Weiss M, Loprinzi CL, Creagan ET, Dalton RJ, Novotny P, O’Fallon JR. Utility of follow-up tests for detecting recurrent disease in patients with malignant melanomas. J Am Med Assoc 1995; 274: 1703–5. 4 Basseres N, Grob JJ, Richard MA, 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: 199–203. 5 Mooney MM, Kulas M, McKinley B, Michalek AM, Kraybill WG. Impact on survival by method of recurrence detection in stage I and II cutaneous melanoma. Ann Surg Oncol 1998; 5: 54–63. 6 Rumke P, van Everdingen JE. Consensus on the management of melanoma of the skin in the Netherlands, Dutch Melanoma Working Party. Eur J Cancer 1992; 28 (2–3): 600–4. 7Orfanos CE, Jung EG, Rassner G, Wolff HH, Garbe C. Position and recommendations of the Malignant Melanoma Committee of the German Society of Dermatology on diagnosis, treatment and after-care of malignant melanoma of the skin. Status 1993–94. Hautarzt 1994; 45: 285–91. 8 Ross MI. Staging evaluation and surveillance for melanoma patients in a fiscally restrictive medical environment: a commentary [Review with 43 references]. Surg Clin North Am 1996; 76: 1423– 32. 9 Sackett DJ, Haynes RB, Guyatt GH, et al. Clinical Epidemiology: A Basic Science for Clinical Medicine, 2nd edn. London: Little, Brown, 1991. 10 Kuhns LR, Thornbury JR, Fryback DG. Decision Making in Imaging. Chicago: Yearbook Medical, 1989. 11 Vollmer RT. Malignant melanoma: a multivariate analysis of prognostic factors. Pathol Annu 1989; 24: 383–407. 12 Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 1992; 8: 400–14. 13 Morton DL, Davtyan D, Wanek LA. Multivariate analysis of the relationship between survival and the microstage of primary melanoma by Clark level and Breslow thickness. Cancer 1993; 71: 3737–43. 14 Buttner P, Garbe C, Bertz J, et al. Primary cutaneous melanoma: optimized cutoff points of tumor thickness and importance of Clark’s level for prognostic classification. Cancer 1995; 75: 2499–506. 15 Balch CM, Buzaid AC, Soong S et al. Final version of the American Joint Committee on cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3635–48. 16 Balch CM, Soong S, Shaw HM, Balch CM, Houghton AN, Milton GW, eds. An analysis of prognostic factors in 8500 patients with cutaneous melanoma. In: Cutaneous Melanoma, 2nd edn. Philadelphia: Lippincott Co, 1992: 439–67. 17 Barth A, Wanek LA, Morton DL. Prognostic factors in 1521 melanoma patients with distant metastases. J Am Coll Surg 1995; 181: 193. 18 Kersey PA, Iscoe NA, Gapski JA, et al. The value of staging and serial follow-up investigations in patients with completely resected, primary, cutaneous malignant melanoma. Br J Surg 1985; 72: 614–7. 19 Terhune MH, Swanson N, Johnson TM. Use of chest radiography in the initial evaluation of patients with localized melanoma [see comments]. Arch Dermatol 1998; 134: 569–72. 20 Collins CD, Padley SP, Greenwell F, Phelan M. The efficacy of a single posteroanterior radiograph in the assessment of metastatic pulmonary melanoma. Br J Radiol 1993; 66: 117–19. 21 Buzaid AC, Sandler AB, Mani S, et al. Role of computed tomography in the staging of primary melanoma. J Clin Oncol 1993; 11: 638–43. 22 Moloney DM, Gordon DJ, Briggs JC, Rigby HS. Recurrence of thin melanoma: how effective is follow-up? Br J Plast Surg 1996; 49: 409–13. 23 Mooney MM, Mettlin C, Michalek AM, Petrelli NJ, Kraybill WG. Life-long screening of patients with intermediate- thickness cutaneous melanoma for asymptomatic pulmonary recurrences: a cost-effectiveness analysis. Cancer 1997; 80: 1052–64. 24 Johnson RC, Fenn NJ, Horgan K, Mansel RE. Follow-up of patients with a thin melanoma. Br J Surg 1999; 86: 619–21. 25 Kanzler MH. Initial evaluation of melanoma: don’t stop getting that chest X- ray Yet [letter]. Arch Dermatol 1999; 135: 1121–2. 26 Jillella A, Mani S, Nair B, et al. The role for close follow-up of melanoma patients with AJCC stages I-III: a preliminary analysis [Abstract]. Proc Am Soc Clin Oncol 1995; 14: 413. 27 Soong SJ, Shaw HM, Balch CM, McCarthy WH, Urist MM, Lee JY. Predicting survival and recurrence in localized melanoma: a multivariate approach. World J Surg 1992; 16: 191–5. 28 Slingluff CL, Dodge RK, Stanley WE, Seigler HF. The annual risk of melanoma progression. Cancer 1992; 70: 1917. 29 Sylaidis P, Gordon D, Rigby H, Kenealy J. Follow-up requirements for thick cutaneous melanoma. Br J Plast Surg 1997; 50: 349–53. 30 Buzaid AC, Tinoco L, Ross MI, Legha SS, Benjamin RS. Role of computed tomography in the staging of patients with local–regional metastases of melanoma. J Clin Oncol 1995; 13: 2104–8. IMAGING AND INVESTIGATION OF MELANOMA PATIENTS 149 31 Kuvshinoff BW, Kurtz C, Coit DG. Computed tomography in evaluation of patients with stage III melanoma. Ann Surg Oncol 1997; 4: 252–8. 32 van den Brekel MW, Pameijer FA, Koops W, Hilgers FJ, Kroon BB, Balm AJ. Computed tomography for the detection of neck node metastases in melanoma patients. Eur J Surg Oncol 1998; 24: 51–4. 33 Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma patients with whole-body 18F- fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients [see comments]. Cancer 1998; 82: 1664–71. 34 Holder WD Jr, White RL Jr, Zuger JH, Easton EJ Jr, Greene FL. Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 1998; 227: 764–9; discussion 769–71. 35 Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[18F]-2-deoxy- D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 1998; 16: 1770–6. 36 Wagner JD, Schauwecker D, Davidson D, et al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol 1999; 17: 1508–15. 37 Calabro A, Singletary SE, Balch CM. Patterns of relapse in 1001 consecutive patients with melanoma nodal metastases. Arch Surg 1989; 124: 1051–5. [...]... I or II melanoma J Clin Oncol 1998; 16 (6) : 2253 60 Wang X, Heller R, VanVoorhis N et al Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma Ann Surg 1994; 220 (6) : 768 –74 Shivers SC, Wang X, Li W et al Molecular staging of malignant melanoma: correlation with clinical outcome J Am Med Assoc 1998; 280 ( 16) : 1410–5 Uren R, Howman-Giles... Engl J Med 1977; 297: 62 7–30 15 Veronesi U, Adamus J, Bandiera DC et al Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities Cancer 1982; 49: 2420–30 16 Wanebo HJ, Woodruff J, Fortner JG 17 18 19 20 21 22 23 24 25 26 Malignant melanoma of the extremities: a clinicopathologic study using levels of invasion (microstage) Cancer 1975; 35: 66 6– 76 Balch CM, Cascinelli... 19 86; 61 : 69 7–705 Balch C, Soong S, Bartolucci A et al Efficacy of an elective regional lymph node dissection of 1–4 mm thick melanomas for patients 60 years of age and younger Ann Surg 19 96; 224: 255 63 Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F Immediate or delayed dissection of regional nodes in patients THE MANAGEMENT OF REGIONAL LYMPH NODE RELAPSE 27 28 29 30 31 32 33 34 35 36 37... early stage melanoma Arch Surg 1992; 127: 392–9 Cabanas RM An approach for the treatment of penile carcinoma Cancer 1977; 39: 4 56 66 Reintgen D, Cruse C, Wells K et al The orderly progression of melanoma nodal metastases Ann Surg 1994; 220: 759– 67 Thompson J, McCarthy W, Bosch C et al Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes Melanoma Res... 11: 1751 6 Lingam MK, Mackie RM, Mackay AJ 38 39 40 41 42 43 44 45 46 47 167 Intraoperative lymphatic mapping using patent blue V dye to identify nodal micrometastases in malignant melanoma Reg Cancer Treat 1994; 7: 144 6 Albertini JJ, Cruse CW, Rapaport D et al Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma Ann Surg 19 96; 130: 65 4–8 Mudun... Ernstoff M et al Interferon-alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 168 4 J Clin Oncol 19 96; 14: 7–17 10 Balch CM, Murad TM, Soong SJ et al Tumor thickness as a guide to surgical management of clinical stage I melanoma patients Cancer 1979; 43: 883–8 11 Balch CM et al A prospective randomised trial of 742 melanoma patients comparing... other melanoma- specific markers [34,42] The most obvious advantage of PCR analysis is that the entire lymph node can be potentially evaluated The clinical relevance of PCR findings are still under investigation, but preliminary data suggest that PCRpositive–H&E-negative lymph node patients have survival rates intermediate between those patients who are PCR- and H&E-positive and those who are both PCR- and... dissection in primary malignant melanoma: a matched-pair analysis Melanoma Res 1995; 5: 189–94 Drepper H, Kohler CO, Bastian B et al Benefit of elective lymph node dissection in subgroups of melanoma patients: results of a multicenter study of 361 6 patients Cancer 1993; 72: 741–9 Sim FH, Taylor WF, Pritchard DJ, Soule EH Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomised... melanoma: experience with 468 2 patients [see comments] Ann Surg 1994; 219: 120–30 13 Coates AS, Ingvar CI, Petersen-Schaefer K et al Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma Unit from 1 960 to 1991 J Am Coll Surg 1995; 180: 402–9 14 Veronesi U, Adamus J, Bandiera DC et al Inefficacy of immediate node dissection in stage I melanoma. .. with melanoma Melanoma Res 1994; 4: 395–9 Thompson JF, Uren RF, Shaw HM et al Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy J Am Coll Surg 1999; 189 (2): 195–204 Gershenwald J, Thompson W, Mansfield PF et al Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 61 2 stage I or II melanoma . II cutaneous melanoma. Ann Surg Oncol 1998; 5: 54 63 . 6 Rumke P, van Everdingen JE. Consensus on the management of melanoma of the skin in the Netherlands, Dutch Melanoma Working Party. Eur J. metastases. Ann Surg 1998; 227: 764 –9; discussion 769 –71. 35 Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[ 18F ]-2 -deoxy- D-glucose positron emission tomography in staging. malignant melanoma. J Clin Oncol 1998; 16: 1770 6. 36 Wagner JD, Schauwecker D, Davidson D, et al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma