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/