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Testis Cancer The Management of Residual Masses Post-chemotherapy Dr Manish I. Patel Urologic Oncologist Westmead Hospital / University of Sydney.

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Presentation on theme: "Testis Cancer The Management of Residual Masses Post-chemotherapy Dr Manish I. Patel Urologic Oncologist Westmead Hospital / University of Sydney."— Presentation transcript:

1 Testis Cancer The Management of Residual Masses Post-chemotherapy Dr Manish I. Patel Urologic Oncologist Westmead Hospital / University of Sydney

2 Questions to be Answered. Do all masses have to be resected or can the histology be accurately predicted? Do normal (or minimal) residual masses in the RP need resection? Is a modified template safe? Is nerve sparing safe? Is there a place for surgery post salvage chemo? When do you resect a post-chemo seminomatous mass? Is there any way to predict the histology?

3 NSGCT-Resection of tumor is important. Teratoma: –Chemo-resistant (Baniel et al. JCO 1995) –Resection is curative. –Unpredictable malignant potential- TMT. –Late relapse. Median relapse time is 5-7 years.-flawed by short FU studies.

4 Resection of Viable Cancer is Important. Complete resection for viable GCT –May be curative –Prognostic Predicitive Factors of Outcome In patients with viable cancer on Multivariate analysis. Complete resection Proportion of viable cancer cells Good risk IGCCC criteria

5 Surgery for necrosis is not beneficial. Need to accurately predict those with necrosis. Minimise morbidity of surgery.

6 Accurately predicting the histology of PC residual masses has been difficult. Instit.PolicyNNecrosisTeratomaCancer Resect None71645%42%13% Indiana 70%red+ 1 0 T. -ve23772%23%5% Mass <10mm20470%25%5% SteyerbergPrediction model >70% necrosis Steyerberg JCO 1998 16(1): 269-274 18181%13%7% NetherlandsMass < 10mm and 1 0 T. -ve11476%17%7% MSKCC (old)<10mm + prechemo <=30mm11365%30%5% NRH<20mm+ 1 0 T. –ve+ prechemo markers normal 5288%4%8% ReHit Study Group 716 PC RPLND Histology from 6 centers. >90% residual masses >5mm Histology of mass not resected by various policies

7 PC-RPLND Good Risk (IGCCCG) Patients Histology of Residual Retroperitoneal Mass Size: MSKCC Residual RP Mass Size TotalCancerTeratomaMalignant Transformation Necrosis No Mass41015 (37%)026 (63%) <2cm1017 (7%)26 (26%)2 (2%)66 (65%) > 2cm and <5cm413 (7%)21 (51%)017 (42%) >5cm and <10cm173 (18%)10 (59%)04 (24%) >10cm and <20cm503 (60%)1 (20%) Total20513 (6%)75 (37%)3 (2%)114 (56%) Patel et.al. presented AUA 2003

8 PC-RPLND Good Risk (IGCCCG) Patients Presence of Teratoma in the Residual RP Mass Residual Mass <2cm and Histology of Primary Tumor Residual Retroperitoneal Mass Size Teratoma in Primary Total Teratoma in Retroperitoneum No Mass +-+- 18 23 10 (56%) 5 (22%) >0cm and <0.5cm +-+- 6666 1 (17%) 2 (33%) >0.5cm and <1.0cm +-+- 8 16 2 (25%) 4 (25%) >1.0cm and <1.5cm +-+- 8787 3 (38%) 1 (14%) >1.5cm and >2.0cm +-+- 6 12 5 (83%) 0 Total +-+- 46 64 21 (46%) 12 (19%) Patel et.al. presented AUA 2003

9 87 patients with PC masses <=20mm. 23 patients mass<=5mm All had RPLND Increasing incidence of teratoma with size of mass. No significant pre or post PC factor predicted necrosis.

10 Decision analysis model predicts increased survival with resection of minimal residual masses. Decision analysis model for estimating survival achieved by resection or observation of minimal residual masses. According to the model: Survival=+2 years with resection of masses 10-20mm. Survival=+1 year with resection of masses 0-10mm.

11 Indiana University Outcomes of patients with RP disease who underwent induction chemotherapy Median FU approx 4 years. A: No residual mass (n=78). OBSERVE 5/78 NED patients: recurrent disease. 4/5 in RP B: Unresectable (n=50). Mainly marker elevation. C: Residual mass, 1 0 Teratoma +ve (n=90).RPLND 10 did not have RPLND. 8/86 NED patients relapsed. 6 distant, 2 in RP. D: Residual mass, 1 0 Teratoma –ve, <90% radiographic PR (n=50).RPLND 5/48 NED patients relapsed. 1 in RP E: Residual mass, 1 0 Teratoma –ve, >90% radiographic PR (n=27).OBSERVE 2/23 NED patients relapsed Survival

12 Complete Resection after Salvage Chemotherapy is Paramount! 580 PC-RPLND at Indiana University. –417 after induction chemo.(markers normal) 10% viable cancer rate. –163 after salvage chemotherapy (markers normal) 55% (90) viable cancer rate. –53/90 were able to be completely resected. »25 had adjuvant chemotherapy: only 9 (36%) cNED »28 had no adj. Chemotherapy: 23 (43%) cNED –All incompletely resected patients died. Imperative to resect all post-salvage chemo masses. Must attempt complete resection as post-op Chemo does not appear effective. Fox et.al. JCO 1993; 11(7): 1294

13 Desperation Surgery Has A Place. When all chemotherapy options have been exhausted, surgical resection is an option. –Solitary RP masses have a much better outcome. 2 studies Murphy and Wood. –63 patients underwent desperation surgery. –50/63 had a complete resection. 17/50 (34%) are cNED with no further therapy. 6/50 (12%) are NED with further chemotherapy. Murphy et.al.J Clin Oncol, 11:324, 1993 Wood et al. Cancer, 70: 2354, 1992

14 What type of surgery is required? With extensive prechemo disease in the RP, a full bilateral dissection is required. –The incidence of tumor away from the primary landing zone or main mass is common. (Donohue 1982 JUrol 127) The dissection may be limited when the prechemo disease is minimal and limited to the primary landing zone. –Advantage: limited morbidity –Disadvantage: RP recurrence

15 Only a small number of non-palapable tumors will be located outside the modified dissection template. Herr et.al. J Urol. 1992;148(6):1812-5 Studied 113 patients.PC RPLND for initial bulky disease. –Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14/ 60 with residual disease. –But tumor was present within a palpable mass in 6/14 patients. –If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 8% would have tumor left in the retroperitoneum. Rabbani et.al. BJU. 1998; 81(2): 295-300 50 patients undergoing PC-RPLND –39=BRPLND. 1 patient had tumor outside modified template. –9= modified RPLND. No recurrence with 55month FU. –2= lumpectomy. 1 pt had recurrence.

16 Frozen section maybe useful during PC-RPLND. Does necrosis on frozen-section analysis of a mass after chemotherapy justify a limited retroperitoneal resection in patients with advanced testis cancer? HERR, H. W. BJU. 1997; 80(4): 653-657. 62 PC-RPLND patients. Underwent modified RPLND if residual mass showed necrosis only. 89% concordance between FS and final parraffin section. 4 false negatives, all specimen confined. 6 years media FU: 14 relapses, 1 in the RP.

17 Nerve-sparing PC-RPLND is safe. Ejaculatory status of 81 patients after nerve sparing PC-RPLND. 35 months FU –6 recurrences –0 in RP. This data confirmed by SD Fossa’s data BJC 1999 80(1/2): 249-255 Lumber nerve roots spared Antegrade Ejaculation Total Patients All Right80%30 3 right92%12 2 right67%6 1 right0%1 All Left70%20 3 Left67%3 2 Left75%4 Bilateral All80%5 Coogan CL.JUrol. 1996; 156(5) :1656-1658.

18 75%-89% incidence of necrosis in lung if necrosis in RP. Brenner et.al. JCO 1996 14(6): 1765 24 patients with simultaneous PC-RP and chest + neck resection. 6 (25%) patients had discordent pathology. Toginini et.al. JUrol 1998 159(6): 1833 143 patients with simultaneous PC-RP and chest resection. 77.5% had the same pathological condition in the chest. 7/40 patients showing RP necrosis has viable cancer in their chest. Steyerberg et.al.JUrol 1997 158(2): 474 159 patients undergoing PC-RP and thoracotomy. Neither size nor degree of shrinkage was predicitive of chest pathology. Necrosis in RP correlated with necrosis in chest 89%. Steyerberg et.al. Cancer 1997 79(2). 215 patients, 6 centers (ReHit study).- Predictors of necrosis. no teratoma in primary, normal prechemo markers and single unilateral mass. RP histology is not sufficiently accurate to eliminate the need to resect chest masses.

19 Management of Post-Chemo Seminomatous Mass.-MSKCC Observation n=3 Surgery n=27Surgery n=28 Observation n=46 Seminoma=6 Teratoma=2 Necrosis=28 Relapsed in RP N=2 No relapse Herr et.al. JUrol 1997 157(3): 860 Puc et.al JCO 1996 14(2): 454

20 Complete Resection is Important. 55 patients PC-RPLND 23 well defined masses –18 C. Resection.(78%) –6 positive histology. 32 poorly defined mass. –14 C. Resection.(44%) –2 positive histology. Ravi et.al BJU 1999 Advocated not resecting ill defined masses. All who relapse DOD All incomplete resections DOD

21 Management of Post-Chemo Seminomatous Mass.-Indiana University NED n=8 Relpase n=1NED n=11 relapse n=1 Schultz et.al. JCO 1990 8(4): 756 Approx 50% of non-resected masses completely resolved a median of 12 months form chemotherapy

22 Prospective studies show a low relapse rate for residual masses =>3cm. DeSantis. JCO 2004; 22:1034-1039

23 FDG-PET is useful in masses >3cm. FDG PET studies in 51 patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses, were correlated with either the histology of the resected lesion or the clinical outcome Supported by other studies in post induction chemotherapy patients. DeSantis. JCO 2004; 22:1034-1039

24 Best Practise. Resect all radiographically visible NSGCT residual masses. Consider resecting normal RP if the primary tumor is teratoma positive. Modified template dissection is safe in small masses in the landing zone. Nerve sparing is safe, works and should be performed where possible. Surgery post salvage chemotherapy is very important. There is a place for desperation surgery.

25 Best Practise. Retroperitoneal pathology will not sufficiently accurately predict histology at other sites. PC seminoma residual masses <3cm should be observed. PC seminoma residual masses => 3cm should be imaged with FDG-PET. Complete resection is very important for outcome.


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