|
Penyebab paling umum kanker paru adalah paparan dalam jangka waktu yang lama terhadap [[rokok tembakau|asap tembakau]],<ref name="Merck" /> yang menyebabkan 80–90% kanker paru.<ref name="Harrison" /> Bukan perokok mencapai angka 10–15% dari kasus kanker paru,<ref name="Thun" /> dan kasus ini biasanya disebabkan oleh kombinasi antara [[genetik|faktor genetik]],<ref name="MurrayNadel46" /> gas [[radon]],<ref name="MurrayNadel46" /> [[asbestos]],<ref name="O'Reilly" /> dan [[polusi udara]]<ref name="MurrayNadel46" /> termasuk [[merokok pasif|asap rokok pasif]].<ref name="AUTOREF" /><ref name="AUTOREF1" /> Kanker paru dapat dilihat melalui [[foto rontgen dada]] dan [[tomografi komputer]] (CT scan). [[Diagnosis medis|diagnosis]] dapat dipastikan dengan [[biopsi]]<ref name="Holland-Frei78" /> yang biasanya dilakukan melalui prosedur [[bronkoskopi]] atau dipandu dengan CT. Perawatan dan hasil dalam jangka panjang tergantung pada tipe kanker, [[stadium (patologi)|stadium]] (tingkat penyebaran), dan keadaan kesehatan pasien secara keseluruhan, diukur berdasarkan [[kondisi umum]].
Perawatan biasanya meliputi [[pembedahan]], [[kemoterapi]], dan [[terapi radiasi|radioterapi]]. NSCLC biasanya ditangani melalui pembedahan, sedangkan SCLC umumnya memberikan respons yang lebih baik terhadap kemoterapi dan radioterapi.<ref>{{cite book |last=Chapman |first=S |coauthors=Robinson G, Stradling J, West S |title=Oxford Handbook of Respiratory Medicine |edition=2nd |chapter=Chapter 31 |publisher=Oxford University Press |year=2009 |isbn=9-780199-545162 }}</ref> Secara keseluruhan, 15% dari penduduk di Amerika Serikat terdiagnosa kanker paru [[tingkat harapan hidup|mencapai harapan hidup]] lima tahun setelah diagnosis.<ref name="Collins" /> Secara global, [[kanker]] paru merupakan penyebab utama kematian karena kanker pada laki-laki dan perempuan, dan bertanggung jawab untuk [[:Kategori:Kematian karena kanker paru|1,38 juta kematian]] setiap tahunnya, hingga tahun 2008.<ref name="GLOBOCAN" />
{{TOC limit|limit=3}}
==Penyebab==
Kanker berkembang mengikuti kerusakan genetika pada [[DNA]]. Kerusakan genetika ini mempengaruhi fungsi normal sel, termasuk proliferasi sel, pemrograman kematian sel ([[apoptosis]]) dan perbaikan DNA. Ketika lebih banyak kerusakan terakumulasi, risiko terhadap kanker makin bertambah.<ref name="Holland-Frei8">{{Cite book |last=Brown |first=KM |coauthors=Keats JJ, Sekulic A et al. |title=Holland-Frei Cancer Medicine |publisher=People's Medical Publishing House USA |year=2010 |chapter=8 |edition=8th|isbn=978-1607950141 }}</ref>
===Merokok===
===Asbestos===
[[Asbestos]] dapat menyebabkan berbagai penyakit paru-paru, termasuk kanker paru. Merokok tembakau dan asbestos memberikan efek [[sinergi]]s dalam pembentukan kanker paru.<ref name="O'Reilly" /> Asbestos juga dapat menyebabkan kanker pada [[pleura]], yang disebut [[mesotelioma]] (yang berbeda dari kanker paru).<ref>{{Cite book |last=Davies |first=RJO |coauthors=Lee YCG |title=Oxford Textbook Medicine |publisher=OUP Oxford |year=2010 |chapter=18.19.3 |edition=5th |isbn=978-0199204854 }}</ref>
===Polusi udara===
Polusi udara di luar rumah hanya memberikan efek yang kecil dalam meningkatkan risiko kanker paru.<ref name="MurrayNadel46">{{Cite book |author=Alberg AJ, Samet JM |title=Murray & Nadel's Textbook of Respiratory Medicine |publisher=Saunders Elsevier |year=2010 |chapter=Chapter 46 |edition=5th |isbn=978-1-4160-4710-0 }}</ref> [[Bahan partikel atmosfir|partikulat]] (PM<sub>2.5</sub>) halus dan [[aeorosol sulfur stratosferik|aerosol sulfat]], yang berasal dari pelepasan asap kendaraan bermotor di jalanan, diasosiasikan agak meningkatkan risiko.<ref name="MurrayNadel46" /><ref>{{cite journal |last=Chen | first=H | coauthors=Goldberg MS, Villeneuve PJ | journal=Reviews on Environmental Health | year=2008 |month=Oct-Dec | volume=23 |issue=4 | pages=243–297 | title=A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases | pmid=19235364 }}</ref> Untuk [[nitrogen dioksida]], kenaikan bertahan hingga 10 [[bagian per miliar]] meningkatkan risiko kanker paru hingga 14%.<ref>{{cite journal | last=Clapp | first=RW |coauthors=Jacobs MM, Loechler EL | journal=Reviews on Environmental Health | year=2008 | month=Jan-Mar | volume=23|issue=1 | pages=1–37 | title=Environmental and Occupational Causes of Cancer New Evidence, 2005–2007 | pmid=18557596 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791455/?tool=pubmed | pmc=2791455}}</ref> Polusi udara luar diperkirakan bertanggung jawab terhadap 1–2% kejadian kanker paru.<ref name="MurrayNadel46" />
Bukti tentatif mendukung adanya kenaikan risiko kanker paru dari [[polusi dalam ruang]] yang berhubungan dengan pembakaran kayu, batubara, residu bahan bakar kotoran dan sisa sampah yang dipakai untuk memasak dan pemanas ruang.<ref name=Lim2012>{{cite journal|last=Lim|first=WY|coauthors=Seow, A|title=Biomass fuels and lung cancer.|journal=Respirology (Carlton, Vic.)|date=2012 Jan|volume=17|issue=1|pages=20-31|pmid=22008241}}</ref> Wanita yang terpapar asap pembakaran batubara memiliki risiko dua kali lebih tinggi dan sejumlah produk sampingan dari pembakaran [[tanaman organik]] diketahui atau dicurigai bersifat karsinogen.<ref name=Sood2012/> Risiko ini memengaruhi kurang lebih 2.4 miliar orang di seluruh dunia,<ref name=Lim2012/> dan dipercaya menyebabkan 1.5% kematian karena kanker paru.<ref name=Sood2012>{{cite journal|last=Sood|first=A|title=Indoor fuel exposure and the lung in both developing and developed countries: an update.|journal=Clinics in chest medicine|date=2012 Dec|volume=33|issue=4|pages=649-65|pmid=23153607}}</ref>
===Genetika===
Diperkirakan bahwa 8 hingga 14% dari kanker paru disebabkan oleh faktor [[keturunan|diturunkan]].<ref>{{cite book|last=Dudley|first=Joel|title=Exploring Personal Genomics|year=2013|publisher=Oxford University Press|isbn=9780199644483|page=25|url=http://books.google.ca/books?id=arCnThIq9LcC&pg=PA25}}</ref> Pada orang dengan saudara yang terkena kanker paru, risiko meningkat hingga 2.4 kali. Hal ini disebabkan oleh adanya [[polimorfisme genetik|kombinasi gen]].<ref name="Fishman1802">{{Cite book |author=Kern JA, McLennan G |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |page=1802 |edition=4th |isbn=0-07-145739-9 }}</ref>
===Penyebab lain===
Melakukan [[foto rontgen dada]] adalah salah satu langkah pemeriksaan awal jika seseorang melaporkan gejala-gejala yang mengarah pada kanker paru. Upaya ini bisa menunjukkan adanya massa yang jelas, pelebaran [[mediastinum]] (yang menunjukkan penyebaran ke [[nodus limfatik]]), [[atelektasis]] (kolaps), konsolidasi ([[pneumonia]]), atau [[efusi pleura]].<ref name="Merck" /> [[Tomografi x-ray terkomputerisasi|Pencitraan CT]] umumnya digunakan untuk memberi informasi tambahan tentang jenis dan perluasan penyakit. [[Bronkoskopi]] atau [[biopsi]] dipandu-CT kerap dipakai dalam pengambilan sampel tumor untuk pemeriksaan [[histopatologi]].<ref name="Collins" />
Kanker paru sering tampak sebagai [[nodul paru soliter]] dalam foto rontgen dada. Tetapi, [[diagnosis diferensial]]nya luas. Banyak penyakit lain yang menunjukkan tampilan seperti itu, termasuk [[tuberkulosis]], infeksi jamur, kanker metastatik, atau [[pneumonia terkelompok]]. Penyebab nodul paru soliter yang lebih jarang ditemukan termasuk [[hamartoma]], [[kista bronkogenik]], [[adenoma]], [[malformasi arteriovena]], [[sekuestrasi paru]], [[nodul reumatoid]], [[granulomatosis Wegener]], atau [[limfoma]].<ref>{{Cite book |last=Miller |first=WT |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |page=486 |edition=4th |isbn=0-07-145739-9 }}</ref> Kanker paru juga bisa berupa [[incidentaloma|temuan insidental]], sebagai nodul paru soliter dalam sebuah foto rontgen dada atau CT scan yang dilakukan untuk tujuan yang tidak berkaitan.<ref name="Fishman1815">{{Cite book |last=Kaiser |first=LR |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |pages=1815–1816 |edition=4th |isbn=0-07-145739-9 }}</ref> Diagnosis definitif kanker paru didasarkan pada pemeriksaan [[histopatologi|histologi]] jaringan yang meragukan dalam konteks ciri klinis dan radiologi.<ref name="Harrison" />
===Klasifikasi===
Tiga subtipe utama NSCLC adalah [[adenokarsinoma]], [[karsinoma paru sel skuamosa]], dan [[karsinoma paru sel besar]].<ref name="Harrison" />
Hampir 40% kanker paru adalah adenokarsinoma, yang biasanya bermula di jaringan paru perifer.<ref name="Holland-Frei78">{{cite book |last=Lu |first=C |coauthors=Onn A, Vaporciyan AA et al. |title=Holland-Frei Cancer Medicine |edition=8th |chapter=78: Cancer of the Lung |publisher=People's Medical Publishing House |year=2010 |isbn=9781607950141}}</ref> Kebanyakan kasus adenokarsinoma dihubungkan dengan kebiasaan merokok; namun, di antara orang-orang yang merokok kurang dari 100 rokok sepanjang hidup mereka ("tidak pernah merokok"),<ref name="Harrison" /> adenokarsinoma merupakan jenis kanker paru yang paling umum.<ref name="Subramanian">{{cite journal | last=Subramanian | first=J | coauthors=Govindan R |title=Lung cancer in never smokers: a review | journal=Journal of Clinical Oncology | volume=25 | issue=5 | pages=561–570| publisher=American Society of Clinical Oncology | month=February | year=2007 | pmid=17290066 |doi=10.1200/JCO.2006.06.8015 }}</ref> Satu subtipe adenokarsinoma, [[karsinoma bronkioloalveolar]], lebih umum ditemukan pada wanita yang tidak pernah merokok, dan penderitanya dapat memiliki daya tahan hidup yang lebih baik.
Karsinoma sel skuamosa menjadi penyebab sekitar 30% kanker paru. Jenis ini khususnya timbul di saluran napas besar. Rongga berlubang dan [[nekrosis|kematian sel]] yang berkaitan umumnya ditemukan di pusat tumor. Sekitar 9% kanker paru adalah karsinoma sel besar. Disebut demikian karena sel-sel kanker tersebut besar, memiliki [[sitoplasma]] berlebihan, [[nukleus sel|nuklei]] besar dan [[nukleolus|nukleoli]] kelihatan jelas.
====Lain-lain====
Empat subtipe histologi utama telah diketahui, meskipun sejumlah kanker mungkin mengandung kombinasi beberapa subtipe yang berbeda.<ref name=Robbins>{{cite book |last=Maitra |first=A |coauthors=Kumar V |year=2007 |title=Robbins Basic Pathology|edition=8th |publisher=Saunders Elsevier |pages=528–529 |isbn=978-1-4160-2973-1 }}</ref> Subtipe yang jarang termasuk [[Kanker kelenjar ludah|tumor kelenjar]], [[karsinoid paru|tumor karsinoid]], dan karsinoma tak terdiferensiasi.<ref name="Harrison" />
====Metastasis====
[[Gambar:Lung cancer.jpg|thumb|Contoh [[pneumonektomi]] yang mengandung [[karsinoma sel-skuamosa]], terlihat sebagai daerah putih di dekat bronkus]]
Jika pemeriksaan mengonfirmasi adanya kanker paru bukan-sel-kecil (NSCLC), penilaian [[stadium kanker|stadium]] dilakukan untuk menentukan apakah penyakit tersebut termasuk lokal dan dapat dilakukan pembedahan atau jika sel tersebut telah menyebar ke titik di mana tidak dapat ditangani dengan jalan pembedahan. Pindai tomografi komputer (CT scan) dan [[tomografi emisi positron]] digunakan untuk penentuan ini.<ref name="Harrison" /> Jika dicurigai adanya keterlibatan kelenjar limfa mediastinum, [[mediastinoskopi]] dapat digunakan untuk mengambil sampel nodus dan membantu penentuan stadium.<ref name="Fishman1853">{{Cite book |author=Kaiser LR |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |pages=1853–1854|edition=4th |isbn=0-07-145739-9 }}</ref> [[Tes darah]] dan [[uji fungsi paru]] digunakan untuk menilai apakah seseorang cukup sehat untuk melakukan pembedahan.<ref name="Collins" /> Jika uji fungsi paru menunjukkan cadangan pernapasan yang rendah, pembedahan tidak mungkin dilakukan.<ref name="Harrison" />
Pada sebagian besar kasus kanker paru bukan-sel-kecil (NSCLC) stadium awal, pembuangan lobus paru ([[lobektomi]]) merupakan penanganan bedah pilihan. Pada orang-orang yang tidak siap untuk lobektomi total, eksisi sublobar yang lebih kecil ([[eksisi baji]]) dapat dilakukan. Akan tetapi, eksisi baji memiliki risiko kambuh yang lebih besar daripada lobektomi.<ref name="Fishman1855">{{Cite book |author=Kaiser LR |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |pages=1855–1856 |edition=4th |isbn=0-07-145739-9 }}</ref> [[Brakiterapi]] [[iodin]] radioaktif di bagian tepi eksisi baji dapat mengurangi risiko kambuh.<ref>{{cite journal | last=Odell | first=DD | coauthors=Kent MS, Fernando HC | title=Sublobar resection with brachytherapy mesh for stage I non-small cell lung cancer | journal=Seminars in Thoracic and Cardiovascular Surgery |volume=22 | issue=1 | pages=32–37 | year=2010 | month=Spring | pmid=20813314 | doi=10.1053/j.semtcvs.2010.04.003}}</ref> Jarang sekali dilakukan pembuangan semua paru-paru ([[pneumonektomi]]).<ref name="Fishman1855" /> [[Pembedahan torakoskopi berbantu video (VATS)]] dan [[lobektomi VATS]] menggunakan pendekatan invasif yang minimal pada pembedahan kanker paru.<ref>{{cite journal | last=Alam| first=N | coauthors=Flores RM | title=Video-assisted thoracic surgery (VATS) lobectomy: the evidence base |journal=Journal of the Society of Laparoendoscopic Surgeons | volume=11 | issue=3 | pages=368–374 | year=2007 |month=July–September | pmid=17931521 | pmc=3015831}}</ref> Lobektomi VATS sama efektifnya jika dibandingkan dengan lobektomi terbuka konvensional, dengan rasa sakit pascabedah yang lebih ringan.<ref>{{cite journal | last=Rueth | first=NM | coauthors=Andrade RS |title=Is VATS lobectomy better: perioperatively, biologically and oncologically? | journal=Annals of Thoracic Surgery |volume=89 | issue=6 | pages=S2107–S2111 | year=2010 | month=June | pmid=20493991 | doi=10.1016/j.athoracsur.2010.03.020}}</ref>
Penanganan kanker paru sel kecil (SCLC), biasanya menggunakan kemoterapi dan/atau radioterapi.<ref name='SimonTurrisi'>{{cite journal |author=Simon GR, Turrisi A |title=Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition)|journal=Chest |volume=132 |issue=3 Suppl |pages=324S–339S |year=2007 |month=September |pmid=17873178|doi=10.1378/chest.07-1385 |url=http://chestjournal.chestpubs.org/content/132/3_suppl/324S.long}}</ref> Akan tetapi, peran pembedahan dalam kanker paru sel kecil (SCLC) perlu dipertimbangkan kembali. Pembedahan mungkin meningkatkan keberhasilan jika ditambahkan pada kemoterapi dan radiasi dalam kanker paru sel kecil (SCLC) tahap awal.<ref>{{cite journal | last=Goldstein | first=SD | coauthors=Yang SC | title=Role of surgery in small cell lung cancer | journal=Surgical Oncology Clinics of North America | volume=20 | issue=4 | pages=769–777 | year=2011 |month=October | pmid=21986271 | doi=10.1016/j.soc.2011.08.001}}</ref>
===Kemoterapi===
Panduan [[kemoterapi]] tergantung pada jenis tumor.<ref name="Holland-Frei78" /> Kanker paru sel kecil (SCLC), meski penyakit relatif pada stadium awal, penting ditangani dengan kemoterapi dan radiasi.<ref>{{cite journal |author=Hann CL, Rudin CM |title=Management of small-cell lung cancer: incremental changes but hope for the future |journal=Oncology (Williston Park)|date=2008-11-30|volume=22|issue=13|pages=1486–92 |pmid=19133604}}</ref> Pada SCLC, [[cisplatin]] dan [[etoposide]] adalah yang paling sering digunakan.<ref name="Murray"/> Kombinasi antara [[carboplatin]], [[gemcitabine]], [[paclitaxel]], [[vinorelbine]], [[topotecan]], dan [[irinotecan]] juga digunakan.<ref name="Azim" /><ref name="MacCallum" /> Pada kanker paru bukan-sel-kecil (NSCLC) tahap lanjut, kemoterapi meningkatkan masa tahan hidup dan digunakan sebagai pengobatan urutan pertama, yang diberikan jika seseorang cukup kuat untuk pengobatan tersebut.<ref name="pmid18678835" /> Biasanya, pengobatan ini menggunakan dua obat, yang salah satunya sering berupa obat berbasis platina (baik [[cisplatin]] atau [[karboplatin]]). Obat lain yang biasa digunakan adalah [[gemcitabine]], [[paclitaxel]], [[docetaxel]],<ref name="Fishman1876">{{Cite book |author=Mehra R, Treat J |title=Fishman's Pulmonary Diseases and Disorders |publisher=McGraw-Hill |year=2008 |page=1876 |edition=4th |isbn=0-07-145739-9 }}</ref><ref name="Clegg" /> [[pemetrexed]],<ref name="pmid20446853">{{cite journal |author=Fuld AD, Dragnev KH, Rigas JR|title=Pemetrexed in advanced non-small-cell lung cancer |journal=Expert Opin Pharmacother |volume=11 |issue=8|pages=1387–402 |year=2010 |month=June |pmid=20446853 |doi=10.1517/14656566.2010.482560 }}</ref> [[etoposide]], atau [[vinorelbine]].<ref name="Clegg" />
[[Kemoterapi adjuvan]] merujuk pada penggunaan kemoterapi setelah melakukan pembedahan kuratif untuk menyempurnakan hasilnya. Dalam NSCLC, sampel diambil di dekat [[nodus limfatik]] selama pembedahan untuk membantu [[penentuan stadium kanker paru|penentuan stadium]]. Jika terkonfirmasi penyakit stadium II atau III, kemoterapi adjuvan meningkatkan tingkat kelangsungan hidup sebesar 5% pada lima tahun.<ref name="Carbone">{{Cite journal | last=Carbone | first=DP | coauthors=Felip E | title=Adjuvant therapy in non-small cell lung cancer: future treatment prospects and paradigms | journal=Clinical Lung Cancer | volume=12 | issue=5 | pages=261–271 | month=September |year=2011 | pmid=21831720 | doi=10.1016/j.cllc.2011.06.002 }}</ref><ref name="Le Chevalier">{{Cite journal | last=Le Chevalier | first=T | title=Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? |journal=Annals of Oncology | volume=21 | issue=Suppl. 7 | pages=vii196–198 | month=October | year=2010 | pmid=20943614 |url=http://annonc.oxfordjournals.org/content/21/suppl_7/vii196.long | doi=10.1093/annonc/mdq376}}</ref> Kombinasi vinorelbine dan cisplatin lebih efektif daripada pengobatan lama.<ref name="Le Chevalier" /> Kemoterapi adjuvan untuk penderita kanker stadium IB mengundang kontroversi, karena uji coba klinis belum menunjukkan manfaatnya dengan jelas terhadap kelangsungan hidup.<ref name="Horn" /><ref name="Wakelee" /> Uji coba pra-operasi kemoterapi ([[kemoterapi neo-adjuvan]]) dalam NSCLC yang dapat diangkat belum mencapai suatu kesimpulan.<ref name="Clinical_evidence" />
{{cite web |url=http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional/page2 |title=Non-Small Cell Lung Cancer Treatment |publisher=National Cancer Institute |work=PDQ for Health Professionals |accessdate=2008-11-22}}</ref> Faktor prognostik dalam kanker paru sel kecil termasuk kondisi umum, [[jenis kelamin]], stadium penyakit, dan keterlibatan [[sistem saraf pusat]] atau [[organ hati]] pada saat diagnosis.<ref name="AUTOREF18" />
Untuk NSCLC, prognosis terbaik didapatkan dengan reseksi bedah lengkap penyakit stadium IA, dengan tingkat kelangsungan hidup lima tahun sebesar 70%.<ref name="OTM">{{Cite book |last=Spiro |first=SG |title=Oxford Textbook Medicine |publisher=OUP Oxford |year=2010 |chapter=18.19.1 |edition=5th |isbn=978-0199204854 }}</ref> Untuk SCLC, keseluruhan tingkat kelangsungan hidup lima tahunnya sekitar 5%.<ref name="Harrison" /> Penderita SCLC tingkat ekstensif mempunyai rerata tingkat kelangsungan hidup lima tahun kurang dari 1%. Rerata waktu kelangsungan hidup untuk penyakit stadium terbatas adalah 20 tahun, dengan tingkat kelangsungan hidup lima tahun sebesar 20%.<ref name="Merck" />
Menurut data yang disediakan oleh [[National Cancer Institute]], usia median pada diagnosis kanker paru di Amerika Serikat adalah 70 tahun,<ref>SEER data (SEER.cancer.gov)[http://seer.cancer.gov/csr/1975_2003/results_single/sect_01_table.11_2pgs.pdf Median Age of Cancer Patients at Diagnosis 2002-2003]</ref> dan usia median saat kematian adalah 72 tahun.<ref>SEER data (SEER.cancer.gov)[http://seer.cancer.gov/csr/1975_2006/results_single/sect_01_table.13_2pgs.pdf Median Age of Cancer Patients at Death 2002-2006]</ref> Di AS, orang yang memiliki asuransi kesehatan cenderung mempunyai hasil yang lebih baik.<ref>{{cite journal |last=Slatore | first=CG | coauthors=Au DH, Gould MK | title=An official American Thoracic Society systematic review: insurance status and disparities in lung cancer practices and outcomes | date=November 2010 | journal=American Journal of Respiratory and Critical Care Medicine | volume=182 | issue=9 | pages=1195–1205 | pmid=21041563 |url=http://ajrccm.atsjournals.org/content/182/9/1195.long | doi=10.1164/rccm.2009-038ST}}</ref>
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