Recurrent Gynecological Cancer — What’s Next?

Recurring

Despi­te sur­gery and che­mo­the­ra­py, gyneco­lo­gi­cal tumors such as ova­ri­an, fallo­pian tube, peri­to­ne­um, endo­me­tri­al or cer­vical can­cer can rel­ap­se or recur. This is also pos­si­ble if the ope­ra­ti­on went as smooth­ly as pos­si­ble and the pati­ent respon­ded well to the sub­se­quent che­mo­the­ra­py. In this situa­ti­on, the dise­a­se is usual­ly chro­nic and incura­ble; in ever­y­day cli­ni­cal prac­ti­ce one speaks of a pal­lia­ti­ve situa­ti­on. Howe­ver, various the­ra­pies can be used to stop tumor growth for as long as pos­si­ble, extend life and alle­via­te symptoms.

From a medi­cal point of view, not all recur­ren­ces are the same. The fol­lo­wing fac­tors are important for asses­sing the pro­gno­sis and plan­ning therapy:

• Ailm­ents (sym­ptoms)
• Distance to the last the­ra­py (rel­ap­se-free interval)
• Qua­li­ty and result of the first drug and sur­gi­cal the­ra­py and the other pretreatments
• Gene­ral health
• Side and con­co­mi­tant dise­a­ses (e.g. heart failure)
• After-effects of pre­vious the­ra­pies (e.g. numb­ness of feet and fingers)
• Infor­ma­ti­on on the BRCA sta­tus, this is deter­mi­ned from the blood sam­ple (germ­li­ne muta­ti­ons) and / or tis­sue sam­ple (soma­tic mutations)

The tumors ova­ri­an, fallo­pian tube and peri­to­ne­al can­cer repre­sent a com­mon dia­gno­stic group, they only descri­be dif­fe­rent ana­to­mic­al cha­rac­te­ristics and loca­ti­ons and are iden­ti­cal in terms of their deve­lo­p­ment as well as the sur­gi­cal and medi­cinal can­cer tre­at­ment and are dealt with in a guideline.

What is the tre­at­ment in the cli­nic for recur­rent gyneco­lo­gi­cal car­ci­no­ma? A typi­cal tre­at­ment plan for rel­apsing ova­ri­an can­cer is pro­vi­ded in the fol­lo­wing sections.

1. Dia­gno­sis

The most important exam, if the ova­ri­an can­cer is suspec­ted to come back, is the pel­vic exam, which is done by a skil­led ova­ri­an can­cer spe­cia­list. In addi­ti­on, the anus is then usual­ly exami­ned from the rec­tum. This is fol­lo­wed by an ultra­sound exami­na­ti­on of the vagi­na and abdomen. 

The next step is usual­ly a blood test to deter­mi­ne the tumor mar­ker for ova­ri­an can­cer in the blood. If the values increase here, this can be an indi­ca­ti­on of the recur­rence of the dise­a­se, but is not in its­elf con­clu­si­ve. Rel­ap­se is only pro­ven in com­bi­na­ti­on with evi­dence of the can­cer on exami­na­ti­on or ima­ging. The­re are also stu­dies that have shown that ear­ly tre­at­ment of only ele­va­ted tumor mar­kers, even befo­re the can­cer has shown its­elf, for exam­p­le in a com­pu­ted tomo­gra­phy (CT), has no bene­fit for the pati­ent, i.e. neither the recur­rence-free inter­val nor the sur­vi­val time are exten­ded yours­elf thereby.

CT ima­ging may be neces­sa­ry, but by no means always. In the case of very small, unclear herds, posi­ti­on emis­si­on tomo­gra­phy (PET-CT) may also be used, but this is only very rare­ly necessary.

A his­to­lo­gi­cal exami­na­ti­on is only neces­sa­ry if the source remains unclear in the CT, for exam­p­le. Then a tis­sue sam­ple usual­ly has to be obtai­ned with a local anes­the­tic in the CT and sent to the patho­lo­gist. You look at the tis­sue under the micro­scope and can tell whe­ther it is a benign or mali­gnant growth.

Test­ing for the BRCA 1 or 2 gene modi­fi­ca­ti­on can also be decisi­ve for tre­at­ment plan­ning in ova­ri­an can­cer, as the­re are drugs that can only be used if the­re is a gene­tic modi­fi­ca­ti­on. The gene­tic test­ing for this can be done with a blood sam­ple and also with a tumor sample.

2. Ope­ra­ti­on

An ope­ra­ti­on can also be useful in the event of a rel­ap­se, but only if all sus­pi­cious tis­sue can be remo­ved during such a new ope­ra­ti­on. The­re is a good chan­ce of com­ple­te­ly remo­ving the tumor again if the pati­ent is in good gene­ral con­di­ti­on, the last che­mo­the­ra­py was more than 6 months ago and all visi­ble tumors could be remo­ved during the first ope­ra­ti­on, or this ope­ra­ti­on when the first appeared Ill­ness did not occur at all. A decis­i­on about the ope­ra­ti­on must always be made in a face-to-face mee­ting with the trea­ting sur­ge­on after a phy­si­cal examination.

3. Tumor con­fe­rence & the­ra­py plan­ning discussions

The decis­i­ons for rel­ap­se the­ra­pies are always made tog­e­ther with the head of the cli­nic and the can­cer cen­ter and the enti­re team of the depart­ment, as well as the experts in onco­lo­gy, radio­lo­gy and radia­ti­on the­ra­py in a con­fe­rence that takes place once a week. For this pur­po­se, your case with all docu­ments and pic­tures will be com­pi­led by your trea­ting doc­tor and pre­sen­ted at the con­fe­rence. Based on the­se docu­ments, the­ra­py recom­men­da­ti­ons are made for the pati­ent. The­se recom­men­da­ti­ons take into account the gui­de­lines on ova­ri­an can­cer as well as the latest sci­en­ti­fic fin­dings and available studies.

The result of the con­fe­rence will be explai­ned to you by your doc­tor in a sepa­ra­te appoint­ment. The pati­ent then deci­des tog­e­ther with your doc­tor which the­ra­py is the right one for her and he will explain both the pro­ce­du­re and the side effects befo­re the fur­ther appoint­ments are set.

4. The­ra­py options

When the tumor has retur­ned, the­re are various tre­at­ment opti­ons, for exam­p­le sur­gery fol­lo­wed by che­mo­the­ra­py, che­mo­the­ra­py alo­ne (= mono­the­ra­py), tre­at­ment with che­mo­the­ra­py and tumor vas­cu­lar blo­cka­de, or che­mo­the­ra­py fol­lo­wed by drugs that block the repair mecha­nisms of the tumor cell (PARP ). Which the­ra­py com­bi­na­ti­on is sui­ta­ble depends on the pre­vious the­ra­pies and your sta­te of health and will be dis­cus­sed in the tumor con­fe­rence and then with the patient.

Chemotherapy

Che­mo­the­ra­py, as a the­ra­py that works throug­hout the body, i.e. can poten­ti­al­ly reach every tumor cell, inclu­ding tho­se that can­not be seen or that are in other organs, is the basis of rel­ap­se the­ra­py. If fur­ther che­mo­the­ra­py is neces­sa­ry and pos­si­ble, the recur­rence-free inter­val after the end of the last che­mo­the­ra­py per­for­med is a decisi­ve fac­tor for the choice of the sui­ta­ble che­mo­the­ra­peu­tic agent, as it pro­vi­des infor­ma­ti­on about the sen­si­ti­vi­ty of the tumor to pla­ti­num-based che­mo­the­ra­py. If a tumor responds well to pla­ti­num-based che­mo­the­ra­py, usual­ly car­bo­pla­tin is meant here — the tumor cells are the­r­e­fo­re sus­cep­ti­ble to the mecha­nism of action of the the­ra­py and we speak of pla­ti­num sen­si­ti­vi­ty. In order to clas­si­fy this, one depends on the months sin­ce the last the­ra­py until the recur­rence of the dise­a­se. If the last the­ra­py was more than 6 months ago, one speaks of a pla­ti­num-sen­si­ti­ve rel­ap­se. On the other hand, the­re is pla­ti­num resis­tance if the tumor does not respond, or only weak­ly, to such sub­s­tances and the dise­a­se has retur­ned more quick­ly than 6 months after the last the­ra­py. The pla­ti­num sen­si­ti­vi­ty of a tumor is also an important pro­gno­stic fac­tor and influen­ces the choice of the­ra­py in the rel­ap­sed situation.

1. Pla­ti­num-sen­si­ti­ve tumor

(recur­rence-free inter­val after pla­ti­num-con­tai­ning the­ra­py lon­ger than 6 months after the pre­vious therapy):

• Tre­at­ment with pla­ti­num-con­tai­ning com­bi­na­ti­on the­ra­py pos­si­ble, e.g. com­bi­na­ti­on of car­bo­pla­tin with ano­ther acti­ve ingre­di­ent (e.g. gem­ci­ta­bi­ne or pacli­ta­xel or pegy­la­ted lipo­so­mal doxorubicin)
• In some cases, the anti­bo­dy beva­ci­zu­mab can be admi­nis­te­red (part of the drug the­ra­py), if this has not alre­a­dy been done in the initi­al treatment.

2. Pla­ti­num Resistant Tumor

(Rel­ap­se-free inter­val after pla­ti­num-con­tai­ning che­mo­the­ra­py shorter than 6 months after the pre­vious therapy):

• Chan­ge of medi­ca­ti­on neces­sa­ry to non-pla­ti­num mono­chemo­the­ra­py, e.g. pegy­la­ted lipo­so­mal dox­oru­bicin or topo­te­can or gem­ci­ta­bi­ne or paclitaxel
• If neces­sa­ry, addi­tio­nal admi­nis­tra­ti­on of the anti­bo­dy beva­ci­zu­mab, if this was not admi­nis­te­red in the pre­vious therapy

The dif­fe­rent drugs each have dif­fe­rent typi­cal side effects, so not all drugs in rel­ap­se the­ra­py ine­vi­ta­b­ly lead to hair loss. This may also play a role in the the­ra­py decis­i­on, along with other points.

Targeted therapy with antibodies

This is a tre­at­ment with mole­cu­les, so-cal­led anti­bo­dies, that tar­get cer­tain tar­gets on or in can­cer cells and thus pre­vent the can­cer cells from gro­wing. Anti­bo­dy the­ra­py with beva­ci­zu­mab inhi­bits can­cer growth by sup­pres­sing the for­ma­ti­on of new blood ves­sels. As a result, the can­cer, which needs a lot of blood to grow, is no lon­ger ade­qua­te­ly sup­pli­ed with oxy­gen and nutrients. 

This the­ra­py is usual­ly admi­nis­te­red with che­mo­the­ra­py and can also be con­tin­ued as pre­ser­va­ti­on therapy. 

Pre­ser­va­ti­on the­ra­py with PARP inhi­bi­tors After pla­ti­num-con­tai­ning che­mo­the­ra­py in the rel­ap­se situa­ti­on, so-cal­led PARP inhi­bi­tors can be admi­nis­te­red. The­se can stop the growth of the can­cer cells or lead to the death of the can­cer cell by inhi­bi­ting the DNA repair mecha­nisms of tumors.

Cell divi­si­on crea­tes two iden­ti­cal copies of a cell, each with a com­ple­te set of genes (DNA). During this doubling pro­cess, mista­kes can natu­ral­ly ari­se spon­ta­neous­ly in the dou­ble-stran­ded DNA, e.g. in which pie­ces of the gene­tic infor­ma­ti­on of a sin­gle strand break off. The­se errors in the copy­ing pro­cess are also one of the reasons can­cer can deve­lop in the first place. Nor­mal­ly, the­se errors are cor­rec­ted by genes (for exam­p­le BRCA1 / 2) that are respon­si­ble for the for­ma­ti­on of repair enzy­mes (such as poly-ADP-ribo­se poly­me­ra­se (PARP)). Howe­ver, if the­se genes are modi­fied in such a way that the enzy­mes can­not pro­du­ce them, the repair pro­cess can­not take place. This would be fatal for healt­hy cells, but not so bad for can­cer cells, sin­ce the DNA dama­ge can ulti­m­ate­ly bring tumor growth to a standstill.

So rese­ar­chers have taken the­se pro­ces­ses in the cel­lu­lar micro­c­osm as a model and deve­lo­ped drugs that spe­ci­fi­cal­ly inhi­bit the cancer’s own repair mecha­nisms: the so-cal­led PARP inhi­bi­tors. The­se enzy­me inhi­bi­tors bind to the com­plex of DNA and repair enzy­me of the tumor, so that, among other things, the enti­re dou­ble strand breaks. What is pos­si­ble with nor­mal body cells is not pos­si­ble with can­cer cells: name­ly, repai­ring dou­ble-strand breaks. Ins­tead, the can­cer tri­es to find alter­na­ti­ve ways to repair DNA in order to sur­vi­ve. This also leads to the desta­bi­liza­ti­on of the DNA until the cell is prac­ti­cal­ly dri­ven into “sui­ci­de” and tumor growth comes to a com­ple­te standstill.

The­se rela­tively new PARP inhi­bi­tors work hand in hand with che­mo­the­ra­peu­tic agents that spe­ci­fi­cal­ly cau­se DNA dama­ge in the tumor. 

Anti-hormonal therapy

The growth of some tumor cells is sti­mu­la­ted by hor­mo­nes. Anti-hor­mo­ne the­ra­py aims to block this growth-pro­mo­ting effect of hor­mo­nes. The­re is the pos­si­bi­li­ty of sup­pres­sing the body’s own pro­duc­tion of hor­mo­nes or tar­ge­ting the hor­mo­ne recep­tors (signal recei­vers on the sur­face of cells) on the tumor cells in order to sup­press their effect. In ova­ri­an can­cer, this mild the­ra­py can be used to bridge the­ra­py fati­gue and as an alternative. 

No therapy

Of cour­se, the­re is also the pos­si­bi­li­ty of not con­side­ring any of the tre­at­ment opti­ons descri­bed due to per­so­nal cir­cum­s­tances. In this case, sup­port­i­ve pal­lia­ti­ve care can be considered.

Palliative care

If a dise­a­se has pro­gres­sed that far or has beco­me resistant to the medi­ca­ti­on, the aim of the the­ra­py also chan­ges: one no lon­ger speaks of cura­ti­ve the­ra­py — i.e. a tre­at­ment that aims at a cure — but of pal­lia­ti­ve tre­at­ment. It sup­ports the pati­ent as best as pos­si­ble during the cour­se of the dise­a­se and helps you to deal with and pre­vent side effects that may occur as a result of the can­cer tre­at­ment. Pal­lia­ti­ve the­ra­py aims to reli­e­ve sym­ptoms, slow the pro­gres­si­on of a dise­a­se, and redu­ce other adver­se consequences.

In the con­text of pal­lia­ti­ve medi­cal tre­at­ment, the reduc­tion of pain and the main­ten­an­ce of a good qua­li­ty of life repre­sent a decisi­ve goal: the risks and bene­fits of a fur­ther, com­plex and the­r­e­fo­re stressful the­ra­py should now always be seen in rela­ti­on to the real bene­fit for the pati­ent and her life.

So if “pal­lia­ti­ve” tre­at­ment is used, it does NOT mean that in prin­ci­ple “the­ra­py has ended” and all the­ra­py opti­ons are meanin­g­less. From a purely medi­cal point of view, the cur­rent goal of tre­at­ment is to pro­vi­de the best pos­si­ble qua­li­ty of life and that with the lon­gest pos­si­ble life­span. This can be for a lon­ger peri­od of time becau­se the­re are inde­ed pati­ents who have lived with ova­ri­an can­cer for many years. Alt­hough they have to be trea­ted con­ti­nuous­ly over and over again, they live with an exis­ting, good qua­li­ty of life. 

Pal­lia­ti­ve tre­at­ment aims to pro­vi­de com­pre­hen­si­ve tre­at­ment and to focus par­ti­cu­lar­ly on the indi­vi­du­al pro­blem are­as from which the pati­ents suf­fer most. The­se dif­fer from woman to woman. Pain the­ra­py aims to alle­via­te acu­te and chro­nic pain con­di­ti­ons wit­hout, howe­ver, trea­ting the under­ly­ing ailm­ent that is the cau­se of the pain its­elf. Here, too, the pri­ma­ry goal is to impro­ve the qua­li­ty of life.

5. Stu­dies

The tre­at­ment results for mali­gnant tumors have impro­ved con­sider­a­b­ly in recent years. Cli­ni­cal stu­dies are a pre­re­qui­si­te for new drug appr­oval. In addi­ti­on to com­mon tre­at­ment methods with appro­ved drugs and gui­de­line-based the­ra­py con­cepts, pati­ents have the oppor­tu­ni­ty to take part in cli­ni­cal stu­dies. Cli­ni­cal stu­dies are impe­ra­ti­ve to make pro­gress in can­cer tre­at­ment and to deve­lop the best and most effec­ti­ve the­ra­peu­tic stra­te­gies for pati­ents. Par­ti­ci­pa­ti­on in cli­ni­cal stu­dies can be an advan­ta­ge (qua­li­ty fea­ture & pro­gno­sis fac­tor). In this indi­vi­du­al case, pati­ents should find out about cur­rent and available stu­dies with their trea­ting doctor!

6. The­ra­py control

The the­ra­py results should be che­cked in the midd­le of the plan­ned the­ra­py and at the end. The start­ing point is always the fin­dings, such as the tumor mar­ker value or the exami­na­ti­on results from the gyneco­lo­gi­cal exami­na­ti­on or the CT exami­na­ti­on, which were coll­ec­ted as soon as pos­si­ble befo­re the start of the­ra­py. The­se test results are also cal­led the base­line. In com­pa­ri­son, the fin­dings should sta­bi­li­ze or impro­ve in the midd­le of the plan­ned the­ra­py (usual­ly after 3 cycles, each 3 weeks long), at which point a tumor mar­ker deter­mi­na­ti­on is usual­ly suf­fi­ci­ent and an impro­ved gene­ral con­di­ti­on is also usual­ly a sign of the­ra­py respon­se. If the test results have wor­sened after 3 cycles, the the­ra­py usual­ly has to be chan­ged. At the end of the the­ra­py, the exami­na­ti­ons are repea­ted to assess the respon­se. The­se results are then the new base­line, i.e. the com­pa­ra­ti­ve values for fol­low-up care.

7. Fol­low-up care

After can­cer tre­at­ment, we always recom­mend atten­ding regu­lar medi­cal fol­low-up care. Here, not only are exami­na­ti­ons car­ri­ed out in order to dis­co­ver a recur­rence of the can­cer at an ear­ly stage, but pati­ents should also be sup­port­ed and accom­pa­nied in their the­ra­py-free intervals.

Examination

The fol­low-up exami­na­ti­on for ova­ri­an can­cer con­sists of a con­ver­sa­ti­on in which you are asked about typi­cal sym­ptoms that could be a sign of a recur­rence of the dise­a­se, as well as a gyneco­lo­gi­cal exami­na­ti­on with rec­tal pal­pa­ti­on and a gyneco­lo­gi­cal ultra­sound of the vagi­na and an ultra­sound of the abdo­men.
In addi­ti­on, the tumor mar­ker Ca125 is deter­mi­ned, the cour­se of which, not the indi­vi­du­al value, can also be meaningful.

A CT exami­na­ti­on is only neces­sa­ry if the exami­na­ti­on reve­a­led unclear abnor­ma­li­ties. Fol­lo­wing the exami­na­ti­on, the­re is also the oppor­tu­ni­ty to talk to the doc­tor about topics. It is best to prepa­re inten­si­ve­ly with a few notes to struc­tu­re the conversation.

Pos­si­ble topics for a fol­low-up talk:

• Nut­ri­ti­on
• Sexua­li­ty
• Pre­ven­ti­on
• Reha­bi­li­ta­ti­on
• Deal­ing with my family
• Addi­tio­nal psycho-onco­lo­gi­cal support
• Crea­ti­ve therapies
• Healt­hy living
• Social pro­blems
• Gene­tic predisposition

The sur­vi­vor­ship cli­nic of the gyneco­lo­gi­cal cli­nic is one opti­on for struc­tu­red fol­low-up care for gyneco­lo­gi­cal tumors. More infor­ma­ti­on at:
https://survivorship-clinic.de/