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Invited Review| Volume 158, ISSUE 1, P208-217, July 2020

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Locally advanced squamous cell carcinoma of the vulva: A challenging question for gynecologic oncologists

      Highlights

      • Advanced vulvar carcinoma is based on the primary tumor (T3-T4), or on the presence of bulky, fixed or ulcerated nodes.
      • Preservation of the bowel and/or urinary function without permanent stomas may require multimodality approaches.
      • A personalized approach with RT with/without concurrent chemo and/or surgery may be justified to avoid permanent stomas.
      • A multidisciplinary approach is warranted for patients with locally advanced vulvar carcinoma.

      Abstract

      Squamous cell carcinoma of the vulva is a rare female malignancy, with an incidence increasing with age. Unfortunately, one third of the patients are diagnosed with locally advanced disease, which constitutes a clinical challenge for the clinicians who treat these patients. The main challenges are represented by: 1. The primary site of the disease, which can be proximal to anatomical structures like the anal canal posteriorly, or the urethra and the bladder anteriorly, that in some circumstances cannot be spared without a bowel and/or urinary stoma; 2. The locoregional nodes that can be involved by the tumor, and they can be bulky, fixed or ulcerated; 3. The clinical condition of the patient, who may carry several comorbidities. Treatment modalities include radiation with or without chemotherapy, and surgery. In order to preserve the bowel and the urinary function without a permanent stoma, a personalized management with a multimodality approach is warranted. In this systematic review, we first clarify the different definitions of “locally advanced vulvar carcinoma”. Secondly, we evaluated the different treatment modalities described in the literature, and the impact of the different treatment strategies on prognosis and on preservation of bowel/urinary function. Finally, we offer a possible algorithm that may help the clinicians in treating patients with these uncommon and challenging situations with a multidisciplinary approach.

      Keywords

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      References

        • Gadducci A.
        • Tana R.
        • Barsotti C.
        • Guerrieri M.E.
        • Genazzani A.R.
        Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.
        Crit. Rev. Oncol. Hematol. 2012; 83: 71-83
        • Siegel R.L.
        • KD K.D. Miller
        • Jemal A.
        Cancer statistics, 2017.
        CA Cancer J. Clin. 2017; 67: 7-30
        • Hacker N.F.
        Revised FIGO staging for carcinoma of the vulva.
        Int. J. Gynaecol. Obstet. 2009; 105: 105-106
        • Homesley H.D.
        Management of vulvar cancer.
        Cancer. 1995; 76: 2159-2170
        • Gadducci A.
        • Cionini L.
        • Romanini A.
        • Fanucchi A.
        • Genazzani A.R.
        Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer.
        Crit. Rev. Oncol. Hematol. 2006; 60: 227-241
        • Oonk M.H.M.
        • Planchamp F.
        • Baldwin P.
        • Bidzinski M.
        • Brännström M.
        • Landoni F.
        • Mahner S.
        • Mahantshetty U.
        • Mirza M.
        • Petersen C.
        • Querleu D.
        • Regauer S.
        • Rob L.
        • Rouzier R.
        • Ulrikh E.
        • van der Velden J.
        • Vergote I.
        • Woelber L.
        • van der Zee A.G.J.
        European Society of Gynaecological Oncology guidelines for the management of patients with vulvar cancer.
        Int. J. Gynecol. Cancer. 2017; 27: 832-837
        • Koh W.J.
        • Greer B.E.
        • Campos N.R. Abu-Rustum S.M.
        • Cho K.R.
        • Chon H.S.
        • Chu C.
        • Cohn D.
        • Crispens M.A.
        • Dizon D.S.
        • Dorigo O.
        • Eifel P.J.
        • Fisher C.M.
        • Frederick P.
        • Gaffney D.K.
        • Han E.
        • Higgins S.
        • Huh W.K.
        • Lurain 3rd, J.R.
        • Mariani A.
        • Mutch D.
        • Nagel C.
        • Nekhlyudov L.
        • Fader A.N.
        • Remmenga S.W.
        • Reynolds R.K.
        • Tillmanns T.
        • Ueda S.
        • Valea F.A.
        • Wyse E.
        • Yashar C.M.
        • McMillian N.
        • Scavone J.
        Vulvar cancer, version 1.2017, NCCN clinical practice guidelines in oncology.
        J. Natl. Compr. Cancer Netw. 2017; 15: 92-120
        • Te Grootenhuis N.C.
        • van der Zee A.G.
        • van Doorn H.C.
        • van der Velden J.
        • Vergote I.
        • Zanagnolo V.
        • Baldwin P.J.
        • Gaarenstroom K.N.
        • van Dorst E.B.
        • Trum J.W.
        • Slangen B.F.
        • Runnebaum I.B.
        • Tamussino K.
        • Hermans R.H.
        • Provencher D.M.
        • de Bock G.H.
        • de Hullu J.A.
        • Oonk M.H.
        Sentinel nodes in vulvar cancer: long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I.
        Gynecol. Oncol. 2016; 140: 8-14
        • Thomas G.M.
        • Dembo A.J.
        • Bryson S.C.
        • Osborne R.
        • DePetrillo A.D.
        Changing concepts in the management of vulvar cancer.
        Gynecol. Oncol. 1991; 42: 9-21
      1. C. Kunos, F. Simpkins, H. Gibbons, C. Tian C, H. Homesley. Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial. Obstet. Gynecol., 114 (2009), pp.537–546.

        • Gaffney D.K.
        • King B.
        • Viswanathan A.N.
        • Barkati M.
        • Beriwal S.
        • Eifel P.
        • Erickson B.
        • Fyles A.
        • Goulart J.
        • Harkenrider M.
        • Jhingran A.
        • Klopp A.
        • Koh W.J.
        • Lim K.
        • Petersen I.
        • Portelance L.
        • Small Jr., W.
        • Stewart A.
        • Wiebe E.
        • Wolfson A.
        • Yashar C.
        • Bosch W.
        Consensus recommendations for radiation therapy contouring and treatment of vulvar carcinoma.
        Int. J. Radiat. Oncol. Biol. Phys. 2016; 95: 1191-1200
        • Gill B.S.
        • Bernard M.E.
        • Lin J.F.
        • Balasubramani G.K.
        • Rajagopalan M.S.
        • Sukumvanich P.
        • Krivak T.C.
        • Olawaiye A.B.
        • Kelley J.L.
        • Beriwal S.
        Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: a National Cancer Data Base (NCDB) analysis.
        Gynecol. Oncol. 2015; 37: 365-372
      2. N.F. Hacker, P.J. Eifel, J. van der Velden. Cancer of the vulva. Int. J. Gynecol. Obstet., 131 (Suppl. 2), pp; S76– S83.

      3. S. Polterauer, R. Schwameis, C. Grimm, P. Hillemanns, J. Jückstock, F. Hilpert F, N. de Gregorio, A. Hasenburg, J. Sehouli, S.T. Fürst, H.G. Strauß, K. Baumann, F. Thiel, A. Mustea, P. Harter, P. Wimberger, H. Kölbl, A. Reinthaller, L. Woelber, S. Mahner. Lymph node ratio in inguinal lymphadenectomy for squamous cell vulvar cancer: Results from the AGO-CaRE-1 study Gynecol. Oncol., 153 (2019), pp. 286–291.

        • Podratz K.C.
        • Symmonds R.E.
        • Taylor W.T.
        • Williams T.J.
        Carcinoma of the vulva: analysis of treatment and survival.
        Obstet. Gynecol. 1983; 61: 63-74
        • Beller U.
        • Quinn M.A.
        • Benedet J.L.
        • Creasman W.T.
        • Ngan H.Y.S.
        • Maissoneuve P.
        • Pecorelli S.
        • Odicino F.
        • Heintz A.P.M.
        Carcinoma of the vulva.
        Int. J. Gynecol. Obstet. 2006; 95: s7-s27
        • van der Steen S.
        • de Nieuwenhof H.P.
        • Massuger L.
        • Bulten J.
        • de Hullu J.A.
        New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis.
        Gynecol. Oncol. 2010; 119: 520-525
        • Tabbaa Z.M.
        • Gonzalez J.
        • Sznurkowski J.J.
        • Weaver A.L.
        • Mariani A.
        • Cliby W.A.
        Impact of the new FIGO 2009 staging classification for vulvar cancer on prognosis and stage distributionGynecol.
        Oncol. 2012; 127: 147-152
        • Hoffman M.S.
        Squamous-cell carcinoma of the vulva: locally advanced disease.
        Best. Pract. Res. Clin. Obstet. Gynaecol. 2003; 17: 635-647
        • Aragona A.M.
        • Soderini A.H.
        • Cuneo N.A.
        Defining the concept of locally advanced squamous cell carcinoma of the vulva: a new perspective based on standardization of criteria and current evidence.
        J. Gynecol. Oncol. 2014; 25: 272-278
      4. R.L. O'Donnell, L. Verleye, N. Ratnavelu, K. Galaal, A. Fisher. Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the “too difficult to do” box? Gynecol. Oncol., 144 (2017), pp. 438–447.

        • de Mooij Y.
        • Burger M.P.
        • Schilthuis M.S.
        • Buist M.
        • van der Velden J.
        Partial urethral resection in the surgical treatment of vulvar cancer does not have a significant impact on urinary continence: a confirmation of an authority-based opinion.
        Int. J. Gynecol. Cancer. 2007; 17: 294-297
        • Thornton Jr., W.N.
        • Flanagan Jr., W.C.
        Pelvic exenteration in the treatment of advanced malignancy of the vulva.
        Am. J. Obstet. Gynecol. 1973; 117: 774-781
      5. D. Cavanagh, J.H. Shepherd. The place of pelvic exenteration in the primary management of advanced carcinoma of the vulva. Gynecol.Oncol.13 (1982), pp. 318–322.

        • Remmenga S.
        • Barnhill D.
        • Nash J.
        • Bosscher J.
        • Teneriello M.
        • Park R.
        Radical vulvectomy with partial rectal resection and temporary colostomy as primary therapy for selected patients with vulvar carcinoma.
        Obstet. Gynecol. 1991; 77: 577-579
        • Hopkins M.P.
        • Morley G.W.
        Pelvic exenteration for the treatment of vulvar cancer.
        Cancer. 1992; 70: 2835-2838
        • Miller B.
        • Morris M.
        • Levenback C.
        • Burke T.W.
        • Gershenson D.M.
        Pelvic exenteration for primary and recurrent vulvar cancer.
        Gynecol. Oncol. 1995; 58: 202-205
        • Hannes S.
        • Nijboer J.M.
        • Reinisch A.
        • Bechstein W.O.
        • Habbe N.
        Abdominoperineal excisions in the treatment regimen for advanced and recurrent vulvar cancers-analysis of a single-centre experience.
        Indian J. Surg. 2015; 77: 1270-1274
      6. R.C. Boronow, B.T. Hickman, M.T. Reagan, R.A. Smith, R.E. Steadham. Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations. Am. J. Clin. Oncol., 10 (1987), pp.171–181.

        • Hacker N.F.
        • Berek J.S.
        • Juillard G.J.
        • Lagasse L.D.
        Preoperative radiation therapy for locally advanced vulvar cancer.
        Cancer. 1984; 54: 2056-2061
        • Rotmensch J.
        • Rubin S.J.
        • Sutton H.G.
        • Javaheri G.
        • Halpern H.J.
        • Schwartz J.L.
        • Stewart M.
        • Weichselbaum R.R.
        • Herbst A.L.
        Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas.
        Gynecol. Oncol. 1990; 36: 181-184
        • Stecklein S.R.
        • Frumovitz M.
        • Klopp A.H.
        • Gunther J.R.
        • Eifel P.J.
        Effectiveness of definitive radiotherapy for squamous cell carcinoma of the vulva with gross inguinal lymphadenopathy.
        Gynecol. Oncol. 2018; 148: 474-479
      7. K. Mazumder, A. Elangovan, B. Rai, V. Suri, V Jain, J Kalra, S. Ghoshal. Conventional radiotherapy and intensity-modulated radiotherapy in carcinoma vulva: An experience from a tertiary medical center of India. South Asian J, Cancer, 8 (2019), pp. 41–43.

      8. G. Thomas, A. Dembo, A. DePetrillo, J. Pringle, I. Ackerman, P. Bryson, J. Balogh, Osborne R, Rosen B, Fyles A. Concurrent radiation and chemotherapy in vulvar carcinoma. Gynecol. Oncol., 34 (1989) pp. 263–267.

        • Berek J.S.
        • Heaps J.M.
        • Fu Y.S.
        • Juillard G.J.
        • Hacker N.F.
        Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva.
        Gynecol. Oncol. 1991; 42: 197-201
        • Scheiströen M.
        • Tropé C.
        Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva.
        Acta Oncol. 1993; 32: 657-661
      9. W.J. Koh, H.J. Wallace 3rd, B.E. Greer, J. Cain, K. J. Stelzer, K.J. Russell, H.K. Tamimi, D.C. Figge, A. H. Russell, T.W. Griffin. Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer. Int. J. Radiat. Oncol. Biol. Phys., 26 (1993) pp. 809–816.

      10. P.J. Eifel, M. Morris, T.W. Burke, C. Levenback, D.M. Gershenson. Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Gynecol. Oncol., 59 (1995), pp. 59: 51–56.

      11. G. Lupi, F. Raspagliesi, R. Zucali, R. Fontanelli, D. Paladini, R. Kenda R, F. di Re F. Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma. A pilot study. Cancer, 77 (1996), pp. 1472–1478.

        • Landoni F.
        • Maneo A.
        • Zanetta G.
        • Colombo A.
        • Nava S.
        • Placa F.
        • Tancini G.
        • Mangioni C.
        Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma.
        Gynecol. Oncol. 1996; 61: 321-327
      12. G.S. Leiserowitz, A.H. Russell, W.K. Kinney, L.H. Smith, M.H. Taylor, S.A. Scudder.Prophylactic chemoradiation of inguinofemoral lymph nodes in patients with locally extensive vulvar cancer. Gynecol. Oncol., 66 (1997), pp. 509–514.

        • Moore D.H.
        • Thomas G.M.
        • Montana G.S.
        • Saxer A.
        • Gallup D.G.
        • Olt G.
        Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.
        Int. J. Radiat. Oncol. Biol. Phys. 1998; 42: 79-85
        • Han S.C.
        • Kim D.H.
        • Higgins S.A.
        • Carcangiu M.L.
        • Kacinski B.M.
        Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva.
        Int. J. Radiat. Oncol. Biol. Phys. 2000; 47: 1235-1244
        • Gerszten K.
        • Selvaraj R.N.
        • Kelley J.
        • Faul C.
        Preoperative chemoradiation for locally advanced carcinoma of the vulva.
        Gynecol. Oncol. 2005; 99: 640-644
        • Montana G.S.
        • Thomas G.M.
        • Moore D.H.
        • Saxer A.
        • Mangan C.E.
        • Lentz S.S.
        • Averette H.E.
        Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.
        Int. J. Radiat. Oncol. Biol. Phys. 2000; 48: 1007-1013
      13. A. Gaudineau, D. Weitbruch, P. Quetin, S. Heymann, T. Petit, P Volkmar, F. Bodin, M. Velten, J.F. Rodier JF. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva. Oncol. Lett., 4 (2012), pp. 719–722.

        • Moore D.H.
        • Ali S.
        • Koh W.J.
        • Michael H.
        • Barnes M.N.
        • McCourt C.K.
        • Homesley H.D.
        • Walker J.L.
        A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study.
        Gynecol. Oncol. 2012; 124: 529-533
      14. H.C. van Doorn, A. Ansink, M. Verhaar-Langereis, L. Stalpers. Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst. Rev., Jul 19;(3) (2006): CD003752.

        • Rao Y.J.
        • Chin R.I.
        • Hui C.
        • Mutch D.G.
        • Powell M.A.
        • Schwarz J.K.
        • Grigsby P.W.
        • Markovina S.
        Improved survival with definitive chemoradiation compared to definitive radiation alone in squamous cell carcinoma of the vulva: a review of the National Cancer Database.
        Gynecol. Oncol. 2017; 146: 572-579
        • Natesan D.
        • Hong J.C.
        • Foote J.
        • Sosa J.A.
        • Havrilesky L.
        • Chino J.
        Primary versus preoperative radiation for locally advanced vulvar cancer.
        Int. J. Gynecol. Cancer. 2017; 27: 794-804
      15. H.C. Wagenaar, N. Colombo, I. Vergote, G. Hoctin-Boes, G. Zanett A, S. Pecorelli, A.J. Lacave, Q. van Hoesel, A. Cervantes, G. Bolis, M. Namer, C. Lhommé, J.P. Guastalla, M.A. Nooij, A. Poveda, V Scotto di Palumbo, J.B. Vermorken. Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer. Gynecol. Oncol., 81 (2001), pp. 348–354.

        • Benedetti-Panici P.
        • Greggi S.
        • Scambia G.
        • Salerno G.
        • Mancuso S.
        Cisplatin (P), bleomycin (B), and methotrexate (M) preoperative chemotherapy in locally advanced vulvar carcinoma.
        Gynecol. Oncol. 1993; 50: 49-53
        • Geisler J.P.
        • Manahan K.J.
        • Buller R.E.
        Neoadjuvant chemotherapy in vulvar cancer: avoiding primary exenteration.
        Gynecol. Oncol. 2006; 100: 53-57
        • Raspagliesi F.
        • Zanaboni F.
        • Martinelli F.
        • Scasso S.
        • Laufer J.
        • Ditto A.
        Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva.
        J. Gynecol. Oncol. 2014; 25: 22-29
        • Aragona A.M.
        • Cuneo N.
        • Soderini A.H.
        • Alcoba E.
        • Greco A.
        • Reyes C.
        • Lekmann S.
        Tailoring the treatment of locally advanced squamous cell carcinoma of the vulva: neoadjuvant chemotherapy followed by radical surgery: results from a multicenter study.
        Int. J. Gynecol. Cancer. 2012; 22: 1258-1263
        • Amant F.
        • Nooij L.
        • Annibali D.
        • van Rompuy A.S.
        • Han S.
        • van den Bulck H.
        • Goffin F.
        Brief report on 3-weekly paclitaxel carboplatin efficacy in locally advanced or metastatic squamous vulvar cancer.
        Gynecol. Obstet. Investig. 2018; 83: 620-626
      16. M Cocks M, A Chaux, EG Jenson, JA Miller, MDC Rodriguez Pena, AC Tregnago, D Taheri, ML Eich R Sharma, R Vang, GJ Netto. Immune checkpoint status and tumor microenvironment in vulvar squamous cell carcinoma. Virchows Arch. (2020) Jan 28. doi: https://doi.org/10.1007/s00428-020-02759-y. [Epub ahead of print].

      17. R.W. Naumann, A. Hollebecque, T. Meyer, M.J. Devlin, A. Oaknin J. Kerger, J.M. López-Picazo, J.P.Machiels, JP Delord, T.R.J. Evans, V. Boni, E. Calvo, S.L. Topalian, T. Chen, I Soumaoro, B Li, J Gu, R. Zwirtes, K.N. Moore. Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: results from the phase I/II CheckMate 358 Trial. J Clin Oncol.,37 (2019), 2825–2834.

        • Rogers L.J.
        • Cuello M.A.
        Cancer of the vulva.
        Int. J. Gynaecol. Obstet. 2018; 143: 4-13
        • de Hullu J.A.
        • van der Zee A.G.
        Surgery and radiotherapy in vulvar cancer.
        Crit. Rev. Oncol. Hematol. 2006; 60: 38-58